Clinical Global Impression Of Change Research Articles

Comparison of therapeutic effects of N-Acetylcysteine with pregabalin in improving the clinical symptoms of painful diabetic neuropathy: a randomized, double-blind clinical trial

ObjectivesPainful diabetic neuropathy (PDN) is highly prevalent and annoyingly in patients with diabetes. The aim of this study was to investigate the effects of oral N-acetylcysteine (NAC) compared to pregabalin in PDN.MethodsOne hundred two eligible patients with type 2 diabetes and PDN were randomly recievied pregabalin (150 mg/day) or N-Acetylcysteine (NAC) (600 mg/ twice a day) for 8 weeks. Mean pain score, Sleep interference score (SIS), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and also, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.ResultsNAC was well tolerated in all patients. The decrease in mean pain scores and increase in SIS was similar between two groups. More improvement in PGIC and CGIC from the baseline was reported in NAC group. NAC, significantly, decreased serum levels of MDA, and NO, but increased TAC, TTG, and CAT. Pregabalin, significantly, decreased serum levels of MDA, and NO and increased TAC.DiscussionNAC is efficacious in alleviate symptoms of PDN which is probably related to its antioxidant effects.Trial registrationThe research protocol received approval from the Ethics Committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1397.137). The trial registry URL and number in Iranian Registry of Clinical Trials (IRCT): https://www.irct.ir/trial/33313, IRCT20180814040795N2 (Registration date: 2019-01-21, Retrospectively registered)

Feedback System Analysis of a Multicomponent Intervention on Dyads of Home-Dwelling Persons With Dementia and Their Caregivers: Results From the LIVE@Home.Path Trial.

Proper symptom management, informal caregiver support, and service innovation are required to reduce dementia care burden. The objective of this study is to investigate the effect of the multicomponent LIVE (Learning, Innovation, Volunteering, Empowerment) intervention on caregiver experience of the self-perceived care situation, coordinator performance, and informal care time. We conducted a 24-month multicomponent, stepped-wedge randomized control trial including dyads of people ≥65 years with mild-to-moderate dementia with minimum weekly contact with their informal caregivers in Norway. The intervention was implemented by municipal coordinators over a 6-month period. This study investigates the first 6-month period (September 2019-March 2020) of the trial, due to the coronavirus disease 2019 (COVID-19) pandemic. Primary outcomes are changes in provision of informal care time assessed by Resource Utilization in Dementia Care (RUD) and informal caregiver experience assessed by the Clinical Global Impression of Change (CGIC). We use logistic regression and feedback system analysis to assess the reach of the multicomponent intervention. A total of 280 dyads were included at baseline, mean age of the person with dementia was 81.8 years, and 62.5% were female. After 6 months, the feedback system analysis reveals that the caregivers randomized to the intervention period reported improved caregiver situation (CGIG-T: intervention 0.63 (SD 2.4) vs control -0.43 (SD 1.7), p < .01), even though informal care time for activities of daily living was not reduced (p = .31). Informal caregivers registered a positive change for the Learning, Innovation, and Empowerment components, while no change was found for Volunteer support. Findings illustrate the usefulness of dementia care coordinators that provide regular follow-up. We also show that complex intervention studies benefit from applying feedback system analysis. Meeting the needs of persons with dementia and their caregivers is a complex process that requires coordinated input from health services and user communities. NCT04043364.

Effect of Aerobic Exercise with and without Strengthening Exercises on Neuropathic Symptoms in People with Diabetic Peripheral Neuropathy

Background: The incidence of peripheral neuropathy among chronic diabetic patients is escalating, with a notable rise observed in Pakistan. This trend has been partly attributed to the predominant reliance on pharmacotherapy, while the role of physical exercise in management remains underutilized. Aerobic exercise is widely recommended in clinical guidelines for the treatment and prevention of diabetic complications, and it is hypothesized that the addition of strength training could yield even more benefits. Objective: This study aimed to evaluate the effects of combined aerobic and strength training exercises on neuropathic symptoms in patients with diabetic peripheral neuropathy. Methods: In this randomized clinical trial, 40 patients with diabetic peripheral neuropathy were equally divided into two groups: Group A underwent a combined regimen of aerobic and strength training exercises, whereas Group B engaged in aerobic exercises alone. The effectiveness of these interventions was assessed using the Michigan Neuropathy Screening Instrument (MNSI), Numeric Pain Rating Scale (NPRS), and Clinical Global Impression of Change (CGIC). Data were analyzed using SPSS version 20.0, employing independent t-tests, repeated measures ANOVA, and descriptive statistics for in-depth analysis. Results: Group A demonstrated a significant reduction in MNSI scores with a mean difference of 1.700 and a p-value &lt; 0.001, indicating a substantial improvement in neuropathic symptoms compared to Group B. While both groups showed significant improvements in NPRS and CGIC scores, the differences were not statistically significant, with p-values of 0.599 and 0.330, respectively, and mean differences of 0.1500 and 0.2500 for NPRS and CGIC. The overall statistical analysis revealed a high significance level (p &lt; 0.001) within both groups in all measured outcomes, suggesting considerable improvements post-intervention. Conclusion: The addition of strength training to aerobic exercises significantly enhances the reduction of neuropathic symptoms in diabetic patients. However, for pain relief and overall clinical improvement, both treatment approaches—combined aerobic and strength training or aerobic exercise alone—were equally effective.

FC46: The effectiveness of a multicomponent intervention on caregiver burden and informal care time in home-dwelling people with dementia and their caregivers. Results from the stepped wedge randomized controlled LIVE@Home.Path tria

Background:Deinstitutionalization of nursing care in European counties relies profoundly on the mobilization of the caregivers and municipal homecare services. Yet, caring for home-dwelling people with dementia (PwD) can be stressful and resource demanding. The LIVE@Home.Path trial tailored, implemented, and evaluated the multicomponent LIVE intervention on informal caregivers’ burden in dyads of home-dwelling PwDs and their families.Method:From 2019 to 2021, we conducted a 24-month multicenter, multicomponent, stepped-wedge randomized control trial including dyads of people ≥65 years with mild to moderate dementia with minimum 1h/week contact with their informal caregiver. The user-developed Learning, Innovation, Volunteer support, and Empowerment (LIVE) intervention was implemented by municipal coordinators over 6 months periods. In an intention-to-treat analysis, we applied mixed-effect regression models accounting for time and confounding factors to evaluate the effect of the intervention on Relative Stress Scale (RSS), Resource Utilization in Dementia (RUD) and Clinical Global Impression of Change (CGIC).Results:A total of 280 dyads were included at baseline, mean age of PwD was 82.2 years, 63% female, 43% lived alone, 36% had Alzheimer’s dementia, median MMSE was 20 (range 0-30) and median FAST score 4 (range 1-7). Caregivers were on average 66 years, 64% female, 49% were the PwDs child. At baseline, 80 dyads were randomized to intervention sequence 1 of which 67 received the intervention, corresponding numbers for sequence 2 and 3 were 97/ 57 and 103/50. During the active intervention period, time spent in personal activities of daily living significantly increased with 2.8 hours/months compared to 1.2 hours/months increase in the control period, total score of RSS was stable in the intervention period (0.36 points) (range 0-60), while it increased significantly in the control period (27.0 points), CGIG increased significantly only in the intervention period (0.5 points) (range: -5 worsening, 5 improvement).Conclusion:Although caregivers reported more care time during the intervention periods, they did not experience more stress which may be related to their increased understanding of dementia. Increase in reported care time might also reflect the increased understanding of dementia, leading to more realistic evaluation of own time contribution.

P105: Measuring clinically relevant change in apathy symptoms in ADMET 2

Objective:Treatments trials for apathy in Alzheimer’s disease assess change scores on widely used assessment scales. Here, we aimed to determine whether such change scores on the Neuropsychiatric Inventory - Apathy (NPI-A) scale indicate clinically meaningful change.Methods:Participants completing the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) were included. Participants in this randomized trial received methylphenidate or placebo for 6- months along with a psychosocial intervention. Assessments included Clinical Global Impression of Change in apathy (CGIC-A) and the NPI-A. Participants in both groups with complete data at the six-month visit were included. CGIC-A was assessed as improved (minimal, moderate or marked), no change, or worsened (minimal, moderate or marked). For CGIC-A levels, mean and standard deviation (SD) of the change in NPI-A from baseline was calculated. Spearman correlation determined the association between change in NPI-A and CGIC-A, and Mann-Whitney U tests determined differences between the ‘no change’ group and the ‘improved’ and ‘worsened’ groups. Effect size (mean NPI-A difference between either ‘improved’ and ‘no change’/ SD of overall change) were calculated. Differences were also assessed at 3 months as a sensitivity analysis.Results:Overall, 177 participants were included (median age: 77years, Mini Mental State Examination score: 19.3 (4.8), baseline NPI-A [mean, SD]: 7.9, 2.3), change in NPI-A: -3.7 (3.9). On the CGIC-A, 69 were improved, 82 showed no change, and 26 worsened. The Spearman correlation between NPI-A change and CGIC-A was 0.41 (p= 1x 10-8). The change in NPI-A among participants who improved was -5.3 (4.1) [W=1873, p= 3x10-4], among those who worsened was -1.2 (3.1) (W= 1426.5, p= 0.009) compared to those with no change (-3.2 [3.4]),. The NPI-A score for minimal clinical improvement was -4.5 (4.6) with a small effect size of -0.32, which was consistent at 3-months (-0.31).Conclusion:A minimal clinically significant improvement over 3 and 6-months corresponded to a mean decline of 4.5 points on the NPI-A; however, there is considerable overlap in the NPI-A between levels of clinical impression of change.

Trial of Botulinum Toxin for Isolated or Essential Head Tremor

BackgroundLocal injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials.MethodsIn a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient’s assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to −3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24.ResultsA total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome — improvement by at least 2 points on the CGI scale at week 18 — was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P=0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia.ConclusionsInjection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.)

Multi-trial, aggregated, individual participant data mega-analysis of short-term antidepressant versus mood stabilizer monotherapy of bipolar type II major depressive episode.

Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega-analyses of prospective trials of individual participant-level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy. Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (n = 393) were aggregated into an IPD dataset (i.e., mega-analysis). Hierarchical log-linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI/S) and change (CGI/C) scores, and change over time in Young Mania Rating (YMR) scores. Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (b = -2.33, t = -6.68, p < 0.0001), significantly greater symptom reduction on the CGI/S across time (b = -0.414, t = -6.32, p < 0.001), and a significant improvement in CGI/C across time (b = -0.47, t = -7.43, p < 0.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (b = 0.06, t = 0.49, p = 0.62). Findings from this IPD mega-analysis of bipolar II depression trials suggest a divergence from current evidence-based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega-analysis suggests that antidepressant monotherapy may provide superior short-term effectiveness without clinically meaningful increase in treatment-emergent hypomanic symptoms compared to lithium monotherapy.

Acute Taste Dysfunction in Oropharyngeal Cancer Patients after Transoral Robotic Surgery.

To compare taste changes after transoral robotic surgery (TORS) to taste changes in healthy controls. Oropharyngeal cancer patients receiving TORS and healthy controls were recruited. Participants underwent posterolateral and whole-mouth psychophysical taste testing (identification, intensity, and hedonics) at baseline and at 2 weeks postoperatively (patients) or follow-up (controls). Surgeons reported suspension time and glossopharyngeal nerve injury (GNI) based on the identification and sacrifice of the nerve. A Clinical Global Impression (CGI) of taste symptoms was completed at each session ("My sense of taste bothers me" on a 5-point scale from Never [1] to Always [5]). A taste disorder (TD) was a CGI of 3 (Sometimes) or worse. Within-subject changes in CGI and psychophysical scores were computed. "Worsened taste" was a CGI increase by ≥1 point at follow-up. Of 69 participants, most (33/37 tumor, 31/32 controls) had normal baseline taste (CGI < 3). 14/33 (42%) TORS patients and no controls developed new TDs at follow-up. More smokers (7/9) had worsened taste than nonsmokers (19/60, difference = 46% [95% CI 16%-76%]). More patients without GNI (6/22) than with GNI (0/15) had postoperative phantogeusia (difference = 27% [95% CI 9-45%]). Tumor-ipsilateral taste identification (TI) decreased more in patients (-11.3%) than controls (0.8%, difference = 12.2% [95% CI 5.0-19.3%]). Suspension time was not associated with worsened taste symptoms or psychophysical changes. Patient-reported taste changes after TORS are frequent. Compared to healthy controls, TORS patients have decreased tumor-ipsilateral TI. Suspension time and GNI are unlikely to cause symptomatic TDs. Further investigations of the etiology and long-term symptom burden of TORS-associated TDs will aid in the management of oropharyngeal cancer patients. 3 (non-randomized controlled cohort study) Laryngoscope, 133:3520-3528, 2023.

A Novel, Paresthesia-Free Spinal Cord Stimulation Waveform for Chronic Neuropathic Low Back Pain: Six-Month Results of a Prospective, Single-Arm, Dose-Response Study

ObjectivesThe aim of this prospective, single-blinded, dose-response study was to evaluate the safety and efficacy of a novel, paresthesia-free (subperception) spinal cord stimulation (SCS) waveform designed to target dorsal horn dendrites for the treatment of chronic neuropathic low back pain (LBP). Materials and MethodsTwenty-seven participants with chronic neuropathic LBP were implanted with a commercial SCS system after a successful trial of SCS therapy. Devices were programmed to deliver the investigative waveform (100 Hz, 1000 μs, T9/T10 bipole) at descending stimulation perception threshold amplitudes (80%, 60%, 40%). Programs were evaluated at six, ten, and 14 weeks, after which participants selected their preferred program, with more follow-up at 26 weeks (primary outcomes). Participants were blinded to the nature of the programming. Pain score (visual analog scale [VAS]), Brief Pain Inventory (BPI), quality of life (EQ-5D-5L), and health status (36-Item Short Form [SF-36]) were measured at baseline and follow-ups. Responder rate, treatment satisfaction, clinician global impression of change, and adverse events (AEs) also were evaluated. ResultsMean (± SD) baseline VAS was 72.5 ± 11.2 mm. At 26 weeks (n = 26), mean change from baseline in VAS was −51.7 mm (95% CI, −60.7 to −42.7; p < 0.001), with 76.9% of participants reporting ≥50% VAS reduction, and 46.2% reporting ≥80% VAS reduction. BPI, EQ-5D-5L, and SF-36 scores were all statistically significantly improved at 26 weeks (p < 0.001), and 100% of participants were satisfied with their treatment. There were no unanticipated AEs related to the study intervention, device, or procedures. ConclusionsThis novel, paresthesia-free stimulation waveform may be a safe and effective option for patients with chronic neuropathic LBP eligible for SCS therapy and is deliverable by all current commercial SCS systems. Clinical Trial RegistrationThis study is registered on anzctr.org.au with identifier ACTRN12618000647235.

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6g/dL (p=.003) and P50 left shift of average -11mmHg (p<.0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

0560 Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea: Effect Sizes and Numbers Needed to Treat or Harm

Abstract Introduction Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor that has been shown to activate TAAR1, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150mg/day) or obstructive sleep apnea (OSA) (37.5-150mg/day). Effect size, number needed to treat (NNT) and number needed to harm (NNH) are statistical representations of efficacy and tolerability that clinicians may find helpful in guiding treatment decisions. This analysis characterized these statistical parameters from two registrational studies. Methods We conducted a post-hoc analysis of data from two phase 3 studies in adults with excessive daytime sleepiness associated with narcolepsy (TONES 2) or OSA (TONES 3). Effect size compared to placebo, NNT, and NNH were calculated based on previously published endpoints, post-hoc analyses, and adverse events. Results On the Maintenance of Wakefulness Test, effect size compared to placebo (Cohen’s d) was 0.29, 0.82, and 1.13 for 75mg, 150mg, and 300mg doses of solriamfetol in TONES 2 and 0.46, 0.89, 1.08, and 1.28 for 37.5mg, 75mg, 150mg, and 300mg in TONES 3. On the Epworth Sleepiness Scale (ESS), d was 0.47, 0.80, and 1.02 for 75mg, 150mg, and 300mg in TONES 2, and 0.42, 0.37, 0.99, and 1.04 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. NNT for patients achieving an ESS ≤10 was 7, 5, and 3 for 75mg, 150mg, and 300mg doses in TONES 2 and 8, 6, 4, and 3 for 37.5mg, 75mg, 150mg, and 300mg doses in TONES 3. On the Patient Global Impression of Change (PGIc), NNT was 4, 3, and 3 for 75mg,150mg, and 300mg doses in TONES 2 and 16, 5, 3, and 3 for 37.5, 75mg, 150mg, and 300mg in TONES 3. Similar NNT were found for the Clinician Global Impression of Change as for the PGIc. In both TONES 2 and TONES 3, NNH pooled across doses for adverse events occurring in ≥5% of patients and greater than placebo were all &amp;gt;10, with the exception of headache in TONES 2 (NNH=6). Conclusion This post-hoc analysis demonstrates favorable effect size, NNT, and NNH values for solriamfetol in the treatment of EDS associated with narcolepsy and OSA. Support (if any) Axsome Therapeutics

(184) A Novel, On-demand Therapy for Lifelong Premature Ejaculation using a Miniature Trans-Perineal Electrical Stimulator, the vPatch - a Randomized Controlled Trial

Abstract Introduction While Premature Ejaculation (PE) is a common and disturbing sexual dysfunction in men, currently available treatment modalities have limited efficacy and low treatment adherence. In this study, we assessed perineal Transcutaneous Electrical Stimulation (TES) as a new possibility to treat (PE) Objective To assess the feasibility, safety, and efficacy of vPatch, a miniaturized on-demand perineal (TES) device, for treating PE. Methods We designed a bi-center, international, prospective, randomized, double-blind, two-arm, sham-controlled, first-in-human, clinical study. Calculating for statistical power, 59 patients 21-56 (mean 39.8+9.28) y/o with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in Visit 2, based on IELT values, and medical/sexual history. Eligible patients tried the vPatch to determine the individualized sensory and motor activation thresholds. Patients were randomized to Active (vPatch) and Sham device groups in a 2:1 ratio. During Visit 3, IELTs, Clinical Global Impression of Change (CGIC) scores, and Premature Ejaculation Profile (PEP) questionnaire outcomes were recorded. The vPatch device safety profile was determined by comparing the incidence of treatment-emergent adverse events. Primary endpoints assessed: 1. vPatch device efficacy as mean fold change in geometric mean IELT; each person was compared to themselves, with and without the device, and the Sham group was compared to the Active Group. 2. vPatch safety profile. Secondary endpoints assessed changes in (PEP) before and after treatment and last visit (CGIC) scores. Results Of 59 patients, 51 completed the study, 34 in Active and 17 in Sham Group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (p&amp;lt;0.0001) in the Active Group, as compared to increasing insignificantly from 63 to 81 seconds (p=0.1653) in the Sham Group. IELT significantly increased by 3.22-fold in the Active as compared to the Sham group (p=0.0047). Geometric mean time fold increases of IELT in Active compared to the Sham group were 1.7 (95% CI 1.5-2.1) vs. 1.2 (95% CI 1.0-1.6), respectively. No serious adverse events were reported. According to the CGIC, patients in the active group were significantly more satisfied with the treatment (74% vs. 41%, p=0.0274). The subjects in the active arm reported significant improvement in all 4 PEP parameters (P&amp;lt;0.05). Conclusions We demonstrated the possibility to treat lifelong PE by prolonging coitus on-demand, using electric stimulation of ejaculation muscles with vPatch. This treatment may potentially become an on-demand, non-invasive, and drug-free treatment for PE. Disclosure Yes, this is sponsored by industry/sponsor: Virility LTD, Israel Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Virility LTD, Israel.

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

Medication Preference, Satisfaction, and Clinical Improvement Among Adults Receiving Long-Term Treatment With Rimegepant for Migraine (P10-12.011)

Efficacy of Omaveloxolone in Friedreich’s Ataxia: Post-Hoc Analysis Using Global Statistics Test to Strengthen Secondary Endpoint Analyses (P8-11.011)

<h3>Objective:</h3> We assessed the integrated evidence of efficacy by performing global statistical tests (GSTs) for the primary and secondary endpoints of MOXIe Part 2 (NCT02255435), a 48-week study of the safety and efficacy of omaveloxolone (omav) in patients with Friedreich’s ataxia (FA). <h3>Background:</h3> MOXIe Part 2 showed that omav significantly improved the primary endpoint, modified FA Rating Scale (mFARS) scores, by −2.40 points relative to placebo (p=0.014; n=82). Key secondary endpoints, Patient and Clinician Global Impression of Change (PGIC and CGIC, respectively) demonstrated non-significant but numerically improved results in patients randomized to omav relative to placebo (−0.1 and −0.07, respectively). Omav also improved the secondary endpoint score of FA-Activities of Daily Living (FA-ADL) and achieved nominal statistical significance relative to placebo (−1.3; p=0.042). A GST is an objective way of combining evidence mathematically across multiple endpoints, accounting for redundancy. <h3>Design/Methods:</h3> Two different post-hoc GSTs were performed for MOXIe Part 2. For GST1, the SAP-specified hierarchy was used as the basis for combining the primary and key secondary endpoints (mFARS and PGIC/ CGIC). For GST2, the two most clinically important endpoints were combined (mFARS and FA-ADL). <h3>Results:</h3> A nonparametric, rank-sum test was used for the GSTs. GST1, which combined mFARS, PGIC, and CGIC, resulted in a p-value of 0.0124. GST2, which combined the two most clinically important endpoints, mFARS and FA-ADL, resulted in a p-value of 0.0041. Analysis of mFARS alone using the rank-sum test resulted in a p-value of 0.0280. <h3>Conclusions:</h3> The GSTs integrated evidence from the primary and secondary endpoints and demonstrated stronger evidence of efficacy compared to the primary endpoint alone. This strengthening of evidence occurs when endpoints are directionally consistent with sufficient independence from the primary endpoint, suggesting that secondary endpoints confirm that omav improved the key clinical aspects of FA that were studied. <b>Disclosure:</b> Dr. Hendrix has received personal compensation for serving as an employee of Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pentara Corporation. Dr. Hendrix has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Pentara Corporation. The institution of Dr. Hendrix has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pentara Corporation. Dr. Hendrix has stock in Pentara. Dr. Hendrix has received publishing royalties from a publication relating to health care. Angie Goldsberry has nothing to disclose. Colin Meyer has nothing to disclose. The institution of Dr. Lynch has received research support from reata. The institution of Dr. Lynch has received research support from PTC.

Safety and efficacy of duloxetine versus gabapentin in painful diabetic polyneuropathy

To evaluate safety and efficacy of Gabapentin and Duloxetine in patients with painful diabetic neuropathy.This is a prospective randomized double blinded parallel group study done for a period of 12 weeks. Total of 60 patients were enrolled and randomly allocated to two groups with 30 patients each, group A received Duloxetine 30 mg twice daily and group B received Gabapentin 300mg twice daily and followed every 2 weeks. Patients of age 35 to 60 years with painful diabetic peripheral polyneuropathy are included in the study. Primary objective is improvement in pain assessed by NPRS; Secondary objective is improvement in sleep and clinical condition of the patient, assessed by Sleep Interference Score and Clinical Global Impression of Change (CGIC). Assessment was done at beginning and at four, eight and twelve weeks. Data was analysed using SPSS 12.0 version.Numerical pain rating scores and daily sleep interference scores were reduced significantly with course of treatment within both groups (p = &amp;#60;0.05 in both groups), but there was no significant difference observed between two groups at baseline, 4th week, 8th week and 12th week. There is significant reduction in CGIC severity scores with course of treatment within both groups (p = &amp;#60;0.05 in both groups), but there was no significant difference observed between groups at baseline and at end of treatment. Common adverse events seen are nausea, dry mouth, dizziness, somnolence and constipation in both groups. There is high incidence of nausea and dry mouth with Duloxetine when compared to Gabapentin.Monotherapy with either Duloxetine or Gabapentin was equally effective at 12 weeks treatment with minor side effects. In addition, Gabapentin showed fewer side effects. It can be concluded that for preventing side effects, Gabapentin can be used. Further large head to- head comparator and combination trials are required.

Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute's Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

Active Study: Impact of Voxelotor on Sleep Quality, Physical Activity, and Patient-Reported Outcomes

Background: Sickle cell disease (SCD) is an inherited disorder in which sickle hemoglobin (HbS) polymerization causes red blood cell sickling, resulting in complications such as chronic hemolytic anemia, vaso-occlusion, end-organ damage, and decreased quality of life. Voxelotor is a first-in-class HbS polymerization inhibitor approved in the US for the treatment of SCD in patients aged ≥4 years. The pivotal phase 3 HOPE and phase 2a HOPE-KIDS 1 trials demonstrated the safety and efficacy of voxelotor in increasing hemoglobin (Hb) and decreasing hemolytic markers. Objective: Here we report Hb response, patient-reported quality-of-life (QOL) outcomes, and safety data from the ongoing ActIVe study (NCT04400487), a phase 4, multicenter, open-label study evaluating the effect of voxelotor on physical activity, sleep quality, and overall well-being in patients with SCD. Methods: Patients aged 12 to 55 years with SCD received voxelotor 1500 mg/day for up to 24 weeks across 10 US sites. QOL assessments were completed during baseline (BL) run-in before the start of voxelotor. Hb levels were measured via laboratory assessments at BL and at weeks 2, 12, and 24. The proportion of patients with any increase in Hb from BL was noted. Patient-reported outcomes were evaluated using the Patient Global Impression of Change (PGI-C) scale, the National Institutes of Health Patient-Reported Outcome Measurement Information System-43 (PROMIS-43) for adults (>17 years), PROMIS-37 for adolescents (≤17 years), and a 10-point numeric rating scale (NRS) for pain intensity. A minimum response deemed meaningful was interpreted at the group level as a ≥5-point change from BL (CFB) in PROMIS domains and a ≥2-point change on the NRS. Clinicians' perceptions of the impacts of voxelotor on patients' overall health status were captured using the Clinical Global Impression of Change (CGI-C). All treatment-emergent adverse events (TEAEs) were recorded from the time of consent/assent to 28 days after the last dose of voxelotor. Results: A total of 25 patients were enrolled, with a median (range) age of 20.0 (12-51) years; 64.0% of patients were female and 92.0% were Black or African American. Two (8.0%) patients permanently discontinued voxelotor due to non-compliance and loss to follow-up. A total of 14 of 18 (78%) patients had an increase in Hb at week 24; the mean (SD) increase was 0.53 (0.839) g/dL. Clinicians reported an improvement in health status among 84.6% (11/13) of patients at week 24: 7.7% (1/13) were "very much improved," 46.2% (6/13) were "much improved," and 30.8% (4/13) were minimally improved; 2 patients had no change. At week 24, 92.9% (13/14) of patients self-reported improved health status: 21.4% (3/14) were "very much improved," 42.9% (6/14) were "much improved," and 28.6% (4/14) were minimally improved; 1 patient reported minimally worse health status. At week 24, 14 patients (9 adults, 5 adolescents) completed PROMIS measures; improvements in the mean CFB were reported across several PROMIS health domains. In adults, a meaningful CFB was found for both fatigue and pain interference. Some domains reached near-meaningful improvements, including anxiety, sleep disturbance, and ability to participate (in social roles/other activities), and others improved more modestly (Table 1). While some domains improved among adolescents, none reached a meaningful level (Table 2). A total of 18 (72.0%) patients had ≥1 non-SCD-related TEAE, and 3 (12.0%) patients had ≥1 grade 3 non-SCD-related TEAE. No non-SCD TEAEs of grade 4 or higher were reported. The most common non-SCD-related TEAEs (>10%) were diarrhea (32.0%), headache (20.0%), nausea (20.0%), and vomiting (12.0%). Conclusions: Over three-quarters of voxelotor-treated patients achieved an increase in Hb at week 24, and most patients and clinicians reported improvement in patients' overall health status. The PROMIS data in voxelotor-treated adults provided insights into improvements in general well-being, such as fatigue, pain interference, and ability to participate; most notable were fatigue and pain interference, both of which reached a CFB threshold considered meaningful. The safety profile reported in ActIVe is consistent with previous studies of voxelotor treatment. Overall, results suggest that voxelotor-treated patients may experience improvements in QOL, including in their physical and emotional well-being. Funding: Global Blood Therapeutics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effects of Levodopa-Carbidopa Intestinal Gel Compared with Optimized Medical Treatment on Nonmotor Symptoms in Advanced Parkinson's Disease: INSIGHTS Study.

Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life. The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD. INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed. Out of 89 patients randomized, 87 were included in the analysis (LCIG, n = 43; OMT, n = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, p < 0.001; OMT, p = 0.005) and PDSS-2 (LCIG, p < 0.001; OMT, p < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II (p = 0.006) and CGI-C (p < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT (p < 0.001; p < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum (n = 2) and stoma-site infection (n = 2) (LCIG). There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile.

A novel, on-demand therapy for premature ejaculation using a miniature trans-perineal electrical stimulator: a randomized-controlled trial

<h3>Objectives</h3> To assess the feasibility, safety, and efficacy of a miniaturized on-demand perineal Transcutaneous Electrical Stimulation (TES) Using the vPatch device, for the treatment of premature ejaculation (PE). <h3>Methods</h3> We designed a bi-center, international, prospective, randomized, double-blind, sham-controlled, clinical study. A total of 59 lifelong PE patients were included. After the screening visit (Visit 1), patients measured their intravaginal ejaculatory latency time (IELT) for a 2-week run-in period and complete the Premature Ejaculation Profile (PEP) questionnaire. At Visit 2, eligible patients tried vPatch to determine the individualized sensory and motor activation thresholds. Patients were randomized into active and sham arms in a 2:1 ratio. At Visit 3, the IELT values and PEP outcomes were recorded again. Clinical Global Impression of Change (CGIC) scores were noted. <h3>Results</h3> Of the patients, 51 completed the study, 34 in the active and 17 in the sham arm. In the active arm the Baseline Geometric Mean IELT (BGMI) was 67 seconds (s) and significantly increased by 56s (standard error (SE) 9s) to 123s (p<.0001). However, in the sham arm the BGMI was 63s and increased insignificantly by 17s (SE 12s) to 80s (p=0.1653). The increase in IELT from base line was 3.22-fold greater in favor of the active arm (p=0.0047). In the active arm 91% (31/34) of the subjects significantly improved their IELT due to treatment compared to baseline. The mean geometric time-fold in IELT, in those positive responders was 2.04 (CI 95% 1.68-2.4). According to the CGIC, patients in the active group were significantly more satisfied with the treatment (74% vs. 41%, p=0.0274). The subjects in the active arm reported significant improvement in all 4 PEP parameters (P<0.05). <h3>Conclusions</h3> IELT values and patient-reported outcome measures can be improved with TES using vPatch. This treatment may become an on-demand, noninvasive, and drug-free therapeutic option for lifelong PE. <h3>Conflicts of Interest</h3> This study was sponsored by Virility Medical Ltd

Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.