Open-label Pilot Study Research Articles

Management of obesity with semaglutide or metformin in patients with antipsychotic-induced weight gain (MOSA): a non-randomised open-label pilot study

BackgroundAntipsychotic-induced weight gain (AIWG) represents a significant clinical challenge for both patients and clinicians, requiring appropriate interventions to prevent or reverse weight gain in patients using antipsychotics. Glucagon-like peptide 1 (GLP-1) agonists represent a novel approach to the management of obesity that has recently attracted considerable attention. Semaglutide (a GLP-1 agonist) has been demonstrated to result in notable weight loss. The present study investigates whether semaglutide is equally effective in achieving weight loss in patients with AIWG.MethodsA prospective, non-randomised cohort study was conducted with the objective of evaluating the efficacy and safety of oral semaglutide for the treatment of AIWG in routine outpatient clinical practice. Subsequently, the results were compared with those of a control group of AIWG patients taking metformin.ResultsAfter 16 weeks, the mean body weight loss was 4.5 kg (95% confidence interval (CI), -6.7 to -2.3 kg; p < 0.001) in the semaglutide group (n = 10) versus 2.9 kg (95% CI, -4.5 to -1.4 kg; p < 0.001) in the metformin group (n = 26). This corresponds to an average body weight loss of 4% for semaglutide, and 2.5% for metformin. The respective reductions in body mass index (BMI) and waist circumference were -1.7 kg/m2 (95% CI, -2.4 to -1.0 kg/m2; p < 0.001) and -6.8 cm (95% CI, -9.7 to -3.8 cm; p < 0.001) for semaglutide. The observed reductions for metformin were -0.8 kg/m2 (95% CI, -1.4 to -0.3 kg/m2; p = 0.001) and -3.4 cm (95% CI, -5.4 to -1.3 cm; p = 0.001). The differences between the two groups were not statistically significant. In both groups, adverse effects were typically mild and transient, predominantly nausea. Furthermore, psychiatric symptoms were reduced, and quality of life improved.ConclusionsOral semaglutide represents a viable, effective, and safe treatment option for psychiatric patients. However, further investigation is required to corroborate these findings.

Prophylactic 2-week Glecaprevir/Pibrentasvir in Hepatitis C positive to negative kidney transplantation.

Hepatitis C virus (HCV) positive-to-negative kidney transplants (KT) require direct acting antiviral therapy, but the optimal timing and duration remain unclear. We hypothesized that 14-day prophylactic course of glecaprevir/pibrentasvir 300/120mg (GLE/PIB) would be safe and effective at treating donor-derived HCV viremia. This was a prospective, single-center, single-arm, open-label pilot study. 20 adult HCV negative recipients of HCV nucleic acid amplification test positive deceased-donor kidneys (HCV positive-to-negative) received a 14-day course of GLE/PIB, with the first dose pre-transplant. HCV RNA viral loads (VL) were monitored on post-operative days (POD) 1, 3, 7, and 13. If VL was undetectable on POD 13, GLE/PIB was stopped, and if detectable, GLE/PIB was continued to complete an 8-week course. Surveillance monitoring continued after treatment to ensure sustained viral response (SVR). The primary outcome was efficacy of 14-day prophylactic GLE/PIB. Secondary outcomes included patient and allograft survival, the incidence, timing, and clearance of HCV viremia, and safety events. 7/20 subjects (35%) never developed detectable HCV viremia. Only one subject had a detectable, but nonquantifiable, VL on POD 13 and completed an 8-week course. All subjects achieved SVR 12 weeks post-treatment with no relapses through 1-year follow-up. Mean time to undetectable HCV RNA VL was 10.5 (±4.7) days and mean peak VL was 371 (±715) copies/mL. 6-month and 1-year patient and allograft survival were 100% and 95%. A 14-day course of prophylactic GLE/PIB is safe and effective for HCV positive-to-negative KT and may prevent HCV transmission or significantly reduce the VL for those with detectable transmission allowing for rapid clearance within 2 weeks.

The METEMP Protocol: Massed Exposure Therapy Enhanced with MDMA for PTSD

This article describes the rationale and the specific methods for an open label pilot trial of 100 mg MDMA in combination with massed exposure therapy for PTSD, a treatment which involves daily exposure therapy sessions for two weeks which has found to be effectiveWe review the need for novel PTSD treatments and the existing research on MDMA-assisted therapy, and then describe the rationale for this novel treatment approach, including combining MDMA with a gold standard treatment, translational support for this treatment, strong dissemination potential, and strengths of providing massed exposure treatment. The specific methods of the open label pilot study are presented, followed by conclusions and future directions for this research. This study will enroll at least 15 adults with PTSD over the next 2 years in order to identify feasibility and lead to a manual describing how to combine MDMA with exposure therapy, tested in a randomized, placebo-controlled trial, with significant promise for dissemination and improving our ability to treat PTSD. Trial registrationClinicalTrials.gov identifier: NCT05746572

Ruxolitinib cream for discoid lupus erythematosus: an open-label pilot study of ten subjects

Ruxolitinib cream for discoid lupus erythematosus: an open-label pilot study of ten subjects

Acceptance and Commitment Therapy for Hypersexuality: A Pilot Study

Hypersexuality refers to the inability to control sexual desire. Despite it has shown serious consequences for physical, psychological and social health, the evidence of available psychological interventions is still insufficient. In this open-label pilot study, an Acceptance and Commitment Therapy (ACT) intervention was conducted with adults with clinically significant levels of hypersexuality aimed to examine its feasibility and usefulness. The intervention consisted of eight weekly online individual psychological intervention sessions. Outcome self-report measures were administered at baseline, after the intervention and a 3 months follow-up. Behavioral and subjective informed changes in sexual practices were weekly assessed through self-monitoring. Twelve participants (M age = 38.8 ± 11.5 years, 83.3% male, 66.7% homo or bisexual) completed the intervention. The feasibility was found to be good, with all the participants completing the training and high levels of satisfaction. Hypersexuality, psychological flexibility, cognitive fusion and mindfulness scores significantly improved after the ACT intervention, with large effect sizes. Clinically significant changes in hypersexuality were found for the vast majority of participants, besides reductions in the time dedicated to planning and practicing sex and the sexualized drug use. Results indicate that ACT-based interventions may be considered feasible and potentially effective therapeutic alternatives for hypersexuality.

8000 Intestinimonas Butyriciproducens As A New Preventive Therapy For Type 2 Diabetes: a Proof Of Concept Randomized Controlled Trial

Abstract Disclosure: V. Antoniotti: None. M. Caputo: None. E. Mollero: None. A. Antonioli: None. S. Tini: None. M. Manfredi: None. S. Gul: None. N. Bui: None. J. Seegers: None. W. De Vos: None. G. Aimaretti: None. F. Prodam: None. Background. The incidence of type 2 Diabetes Mellitus (T2D) is increasing worldwide. Prevention is possible by changing lifestyle but it’s not effective alone in real life, due to poor compliance over time. New strategies are necessary, mostly for high-risk individuals. Therapeutic microbiology is a further proposed target, and butyrate-producing bacteria can improve metabolic parameters in obese patients. Our study aims to evaluate the effect of Intestinimonas butyriciproducens as a preventive therapy for T2D in prediabetes thanks to its effects in decreasing Advanced Glycation End Products (AGEs), converting sugars and proteins in butyrate, and increasing insulin sensitivity.Methods. The trial is a double-blind, randomized, placebo-controlled (phase 1) and open-label pilot study with two different doses (phase 2) of 26 weeks. I. butyriciproducens (105 CFU/day) or placebo were given for 12 weeks, then subjects in placebo will start the treatment (105 CFU/day), and the other group will increase the dose (108 CFU/day) for 14 weeks. Overweight or obese patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were included. Patients were assessed for clinical, biochemical, and microbiota parameters at the time of recruitment (V1), after phase 1 (V7) and phase 2 (V10), during which the eating and lifestyle habits were also evaluated. No dietary advice was given. Results. Nineteen have completed the study. Treated patients during the first phase had a significant improvement in glucose-insulin metabolism demonstrated through the HOMA Disposition Index (p= 0.0075). Lipid profile also ameliorates in patients treated at a low dose and then at a high dose, particularly decreasing triglycerides (phase 1: p= 0.0212; phase 2: p= 0.0261). The weight and BMI of patients were stable throughout the period of study. Data from Flash glucose Monitoring (FGM) show a more stable glucose, mainly at the end of the study. Serum AGE concentrations showed a trend towards a decrease in treated patients, whereas IL-10 slowly increased without changes in IL-6 and IL-17.Lastly, 10 out of 19 patients after 26 weeks of treatment had a remission in IFG or IGT (52.6%). Conclusions. Intestinimonas butyriciproducens seems to improve insulin sensitivity and triglycerides in treated patients. Intestinimonas butyriciproducens could be a new strategy in the work-up of T2D prevention. Presentation: 6/1/2024

Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study

BackgroundThe enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD). Methods15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions. ResultsOf 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred. LimitationsLimitations include the small sample size, and the uncontrolled and unblinded nature of the study. ConclusionsIn this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04433858.

Tinidazole mouth rinse for the treatment of oral lichen planus: an observational pilot study

BackgroundGiven the limited treatment options available for oral lichen planus (OLP), a study was undertaken to obtain preliminary information on the therapeutic efficacy of tinidazole mouth rinse in patients with OLP.MethodsA prospective, open-label pilot study was conducted to assess the efficacy of thrice-daily tinidazole mouth rinse for one week in OLP patients (n = 27). Reticulation/erythema/ulceration (REU) scores and visual analog scale (VAS) scores were used to measure lesions at baseline and after one week of treatment. Mucosal samples were collected, and the abundance of Fusobacterium nucleatum was quantified using RT-PCR. Statistical analysis using t-test, Wilcoxon signed rank test and Pearson correlation test.ResultsAfter treatment, VAS scores significantly decreased in both reticular (P = 0.03) and erosive OLP patients (P = 0.003). However, REU scores significantly decreased only in erosive OLP patients (P = 0.002). The relative abundance of Fusobacterium nucleatum on the damaged mucosa surface significantly decreased in all OLP patients (P = 0.01). In erosive OLP patients, the triamcinolone group showed a significantly greater improvement in VAS scores compared to the tinidazole group (P = 0.01). However, there was no statistically significant correlation between the relative abundance of Fusobacterium nucleatum and REU scores in OLP patients (r = 0.0754, P = 0.61).ConclusionTinidazole mouth rinse showed potential in reducing disease severity in OLP patients and was well-tolerated, suggesting its viability as a local therapeutic option. However, randomized controlled studies are warranted to confirm these preliminary findings.

Safety and tolerability of a low glycemic load dietary intervention in adults with cystic fibrosis: a pilot study.

To achieve and maintain adequate weight, people with cystic fibrosis (CF) May often consume energy-dense, nutrient-poor foods high in added sugars and refined carbohydrates; however, little is known about the glycemic and metabolic effects of dietary composition in this patient population. The objective of this pilot study was to investigate the safety and tolerability of a low glycemic load (LGL) diet in adults with CF and abnormal glucose tolerance (AGT). Ten adults with CF and AGT completed this prospective, open-label pilot study. Mean age was 27.0 ± 2.1 years, 64% were female, and all had pancreatic insufficiency. Each participant followed his/her typical diet for 2 weeks, then transitioned to a LGL diet via meal delivery service for 8 weeks. The primary outcome was change in weight from baseline to study completion, with safety established if no significant decline was noted. Other key safety outcomes included change in hypoglycemia measured by patient report and continuous glucose monitoring (CGM). Exploratory outcomes included changes in other CGM measures, body composition by dual energy X-ray absorptiometry (DXA), and patient reported outcomes. There were no significant changes in weight or in subjectively-reported or objectively-measured hypoglycemia. Favorable non-significant changes were noted in CGM measures of hyperglycemia and glycemic variability, DXA measures of fat mass, and gastrointestinal symptom surveys. A LGL dietary intervention was safe and well tolerated in adults with CF and AGT. These results lay the groundwork for future trials investigating the impact of low-glycemic dietary interventions on metabolic outcomes in the CF population.

Duodeno-ileal diversion with self-forming magnets in a sutureless neodymium anastomosis procedure (SNAP) for weight recidivism after sleeve gastrectomy: feasibility and 9-month results.

The sleeve gastrectomy (SG) has become the most common bariatric procedure worldwide. However, insufficient weight loss or weight recidivism is frequent, which may require effective and safe revisional procedures. To determine the technical feasibility and safety of a minimally invasive, duodeno-ileal side-to-side anastomosis using a Sutureless Neodymium Anastomosis Procedure (SNAP) for patients with weight recidivism or inadequate weight loss following SG. This is a prospective, single-arm, open-label pilot study that enrolled patients with obesity to assist in weight reduction following an SG performed > 12months prior. For the SNAP, self-assembling magnets were deployed into the ileum (laparoscopically) and duodenum (per-oral endoscopy). Magnets were coupled under laparoscopic and fluoroscopic guidance to create a compression anastomosis. The primary endpoints were technical feasibility, weight loss, and rate of serious adverse events (SAEs). Successful duodeno-ileal diversions were created with SNAP in 27 participants (mean age: 50.6 ± 9.1, mean BMI: 38.1 ± 4.6kg/m2) with no device-related serious adverse events. Upper endoscopy at 3months confirmed patent, healthy anastomoses in all patients. At 9months, patients (n = 24) experienced 11.9 ± 6.2%, 14.5 ± 10.8%, and 17.0 ± 13.9% TBWL at 3, 6, and 9months, respectively. There were no device-related SAEs. The SNAP is technically feasible and relatively safe, with all patients presenting widely patent anastomosis at 3months. Patients experienced a progressive, clinically meaningful weight loss. Further studies are needed to confirm our findings.

Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism.

Autism spectrum condition (ASC) is a neurodevelopmental condition that is only partly responsive to prevailing interventions. ASC manifests core challenges in social skills, communication, and sensory function and by repetitive stereotyped behaviors, along with imbalances in the brain's excitatory (E) and inhibitory (I) signaling. Repetitive transcranial magnetic stimulation (rTMS) has shown promise in ASC and may be a useful addition to applied behavioral analysis (ABA), a gold-standard psychotherapeutic intervention. We report an open-label clinical pilot (initial) study in which ABA-treated ASC persons (n = 123) received our personalized rTMS protocol (PrTMS). PrTMS uses low TMS pulse intensities and continuously updates multiple cortical stimulation locales and stimulation frequencies based on the spectral EEG and psychometrics. No adverse effects developed, and 44% of subjects had ASC scale scores reduced to below diagnostic cutoffs. Importantly, in PrTMS responders, the spectral EEG regression flattened, implying a more balanced E/I ratio. Moreover, with older participants, alpha peak frequency increased, a positive correlate of non-verbal cognition. PrTMS may be an effective ASC intervention, offering improved cognitive function and overall symptomatology. This warrants further research into PrTMS mechanisms and specific types of subjects who may benefit, along with validation of the present results and exploration of broader clinical applicability.

Treatment of moderate-to-severe canine atopic dermatitis with modified-release mycophenolate (OKV-1001): A pilot open-label, single-arm multicentric clinical trial.

Mycophenolate is an immunomodulating agent successfully used for the treatment of moderate-to-severe atopic dermatitis (AD) in people. Mycophenolate is an effective steroid-sparing treatment option for use in dogs with inflammatory skin diseases. To evaluate whether once-daily modified-release mycophenolate (OKV-1001) is safe and effective for treating moderate-to-severe canine AD. Client-owned atopic dogs (n = 9) were enrolled. In an open-label multicentre pilot study, OKV-1001 (30 mg/kg every 24 h) was given orally for ≤84 days. Concomitant tapering doses of glucocorticoids were administered up to Day (D)28. Clinicians assessed Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) on D0, D14, D28, D56 and D84. Body weight and clinical pathological parameters were measured at baseline and at the end of the study. Treatment with OKV-1001 combined with glucocorticoids significantly reduced the severity of AD within two weeks in seven of nine (77.8%) dogs. The mean percentage change from baseline in the CADESI-04 score was 29% (p = 0.009) at D14 (n = 9), 39% (p = 0.008) at D28 (n = 9) and 49% (p = 0.03) at D56 (n = 7) at which point glucocorticoids had been withdrawn. In two dogs the improvement in CADESI-04 was 62% and 23% (respectively) on D84. No significant adverse events including clinical pathological findings were reported. Modified-release mycophenolate (OKV-1001) may represent a promising alternative treatment option for dogs with moderate-to-severe AD. The safety and efficacy profile of OKV-1001 will need to be established in larger, placebo-controlled clinical trials.

The effect of core stabilization exercises on balance and functional performance in individuals with functional ankle instability: An open-label randomized controlled trial

Objectives: The objective of the study was to evaluate the effect of core stabilization exercises on balance and functional performance in functional ankle instability (FAI). Methods: An open-label randomized control pilot study was conducted with 30 FAI participants allocated to two groups. Inclusion criteria were the presence of frequent ankle sprains, sense of give-away of the ankle, and identification of FAI score &gt;11. The experimental group (n = 15) received core stabilization exercises along with conventional exercises, whereas the control group (n = 15) received only conventional exercises. The intervention period was six weeks. The outcome measures for static balance, dynamic balance, and functional performance were the single-leg stance test, modified star excursion balance test (mSEBT), and side hop test, respectively. The assessment was done at baseline and six weeks post-intervention. Results: Within-group analysis showed improvement in the single-leg stance test and all direction reach distances of mSEBT in both groups using the Wilcoxon signed-rank test. Meanwhile, the side hop test revealed no difference between the two groups. A significant improvement was seen in mSEBT and single-leg stance scores (P ≤ 0.05) between the groups using the Mann–Whitney U-test. However, the side hop test showed no significant difference (P &gt; 0.05). Conclusion: The present study concludes that core stabilization exercises improved balance compared to mobility and strengthening exercises. Hence, it is highly recommended that core stability training be implemented as a holistic approach to managing FAI.

Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). To evaluate the efficacy of verdinexor for the treatment of CETL. Eight client-owned animals with CETL. Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. Verdinexor could be considered a safe, palliative treatment for canine CETL.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

A Study on Optimal Frequency and Duration of PRP in Androgenic Alopecia

Background: Platelet-rich plasma (PRP) therapy has emerged as a promising treatment for androgenetic alopecia (AA), addressing the need for effective hair restoration with minimal invasiveness. However, questions remain regarding the optimal frequency and duration of PRP treatment. Objective: This study aimed to assess the impact of PRP therapy on hair density and diameter in AGA patients, considering variations in treatment response across different AGA grades and alopecia durations. Method: A 6-month open-labeled pilot study was conducted on 30 male participants with AGA Grades III-VII. PRP was administered every 15 days for six sessions, and hair parameters were evaluated using trichoscan. Results: The study demonstrated a significant increase in both hair diameter and density over six months of platelet-rich plasma (PRP) therapy for androgenetic alopecia (AGA). Initially, the mean hair diameter was 0.055 mm, rising to 0.075 mm by the study's end, with a substantial increase of 0.021 mm at six months, equating to a 39.85% improvement. Similarly, hair density increased notably from 6.13 to 8.43 hairs per 10 mm², with the most significant rise at the six-month mark, showing a mean increase of 2.3 hairs per 10 mm², reflecting a 39.73% enhancement. All AGA grades experienced increased hair diameter and density, with Grade 5 showing the highest diameter increase (0.03 mm), and Grade 4A exhibiting the highest density increase (3.0 hairs per 10 mm²). Statistical analysis confirmed significant improvements across all grades (p = 0.0446 for diameter; p = 0.0196 for density). Additionally, patients with alopecia durations up to five years experienced the highest improvements in both diameter (0.026 mm) and density (2.68 hairs per 10 mm²), while longer durations showed lower enhancements (p = 0.0485 for diameter; p = 0.0096 for density). Conclusion: PRP therapy demonstrated efficacy across all AGA grades and durations, suggesting its potential as a promising treatment option for AGA. Further research is needed to validate these findings and establish PRP therapy as a standard AGA treatment.

A noninferiority randomized open-label pilot study of 3- versus 7-day influenza postexposure prophylaxis with oseltamivir in hospitalized children

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7–100%) versus 93.6% (95% CI 78.6–99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2–100%) and 93.1% (95% CI 77.2–99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (− 2.8, − 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI − 2.83, − 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

Off-label use of clomiphene citrate to treat anabolic androgenic steroid induced hypogonadism upon cessation among men (CloTASH) – A pilot study protocol

BackgroundNon-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. MethodsIn this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.

A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these “silent” symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.

(053) THE CONSORTIUM FOR THE STUDY OF WOMEN’S SEXUAL WELLNESS: RATIONAL, MISSION AND CALL TO ACTION

Abstract Introduction Female sexual wellness products have been growing and this growth was accelerated during the pandemic and the increased interest in self-care. While trying to find a place in beauty, sexual wellness really is only slightly beauty-adjacent. The beauty industry is built on delivering many products based solely on a promise. Little science is applied in this field to show any MOA or clinical efficacy. However, even in this sector the status quo is being disrupted by the FDAs Modernization of Cosmetic Regulations Act of 2022 (MoCRA). However, sexual wellness products are really more pharma-adjacent, even while using non-pharmaceuticals (nutraceuticals) ingredients. We reviewed all non-device based sexual wellness products that claimed functional benefit and based on these results, we make some recommendations. Objective To challenge the female sexual wellness industry to adopt basic and clinical science in the development and marketing of female sexual wellness products. Methods Over a three-year span, we reviewed the ingredients and claims as well as any clinical trial data on products claiming a functional benefit in sexual desire, arousal and/or orgasm. Following the unsurprising findings, we propose a number of solutions. Results Without naming the companies or products, we found an abundance of unusual products that did not seem to have a scientific rationale for ingredients and virtually all claims were unsubstantiated. Two entities have performed clinical studies. The first is a cannabis company which performed a study without a validated instruments and soft-endpoints, and as expected, there was a 100% response rate. The second entity has performed pre-clinical studies (organ bath and MOA studies) and an open-label pilot study employing a modified FSFI and diary data and efficacy and safety output. However, this was not a randomized, double-blind, placebo-controlled study. Conclusions Seismic changes are happening in the beauty and wellness industry. Female sexual wellness is closely pharma-adjacent and, as such, should adopt the preclinical and clinical trial approach that has already been developed for the evaluation of drugs in female sexual dysfunction. While these agents may only enhance normal function and don’t treat diseases or disorders, the learnings from the last half century in sexual pharmacotherapy are readily adapted to the development and evaluation of sexual wellness products. Vella Bioscience is rapidly moving to follow these principles, as follows: 1. We are performing a three-month RCT with liposomal cannabidiol vs placebo that has been powered to demonstrate statistical and clinical significance. The outcome instruments include both the PROMIS database and diary data. 2. The establishment of the Consortium for the Study of Women’s Sexual Wellness, with the following mission: Bring scientific rigor to the basic science and clinical science research of sexual wellness products, including the utilization of double-blind, placebo-controlled, randomized clinical trials. Support research, education, and public awareness of female sexual health and wellness. Enable healthcare providers and customers to directly access research protocols and validated products for the management of sexual wellness. Critical to this mission are the members of the Scientific Advisory Board of the Consortium, including Alan Altman, MD, FACOG, Anita Clayton, MD, Peter Fodor, MD, FACS, Sheryl Kingsberg, PhD, Cindy Meston, PhD, James Pfaus, PhD, Nicole Prause, PhD, Raymond Rosen, PhD, and James Simon, MD, FACOG. We invite other corporate entities to utilize the consortium and we hope that ISSWSH will adopt these principles as well. Women deserve data and not a promise. Disclosure Yes, this is sponsored by industry/sponsor: Vella Bioscience, Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Vella Bioscience, Inc.