12-week Treatment Research Articles

걷기와 야외기구운동이 고령여성의 염증인자 및 대사증후군 지표에 미치는 영향

This study examined the changes in inflammatory factors and metabolic syndrome indices by applying a 12-week treatment program to investigate the effects of walking and outdoor exercise on inflammatory factors and metabolic syndrome indices in elderly women. To this end, it was divided into an exercise group and a control group, and walking and outdoor equipment exercise were applied to the exercise group, and the control group was used as a comparison group to verify the exercise effect of the exercise group. The treatment program applied 60-minute warm-up and main exercise 4 times a week for 12 weeks. To verify the statistical effect between the two groups, two-way analysis of variance was applied to analyze the time-period interaction between the groups. Through this procedure, the following conclusions were obtained. BR First, in the effect of 12 weeks of walking and outdoor exercise on inflammatory factors in elderly women, it was found that there was a significant interaction effect between the exercise group and control group in IL-6, and TNF-a was also found in the exercise group and control group. It was found that there was a significant interaction effect in the group. BR Second, it was found that there was a significant interaction effect between the exercise group and the control group in TC in terms of the effect of 12 weeks of walking and outdoor machine exercise on metabolic syndrome indices in elderly women. On the other hand, in TG, HDL, and LDL, there was no significant interaction between the exercise group and the control group.

No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta

Bulevirtide (BLV) is a hepatitis D virus (HDV)/hepatitis B virus (HBV) entry inhibitor that has shown virologic response (responder, HDV-RNA undetectable or ≥2 log10 IU/mL decrease from baseline) in >50% of patients after 24-week treatment. However, some patients achieve <1 log10 IU/mL decline in HDV-RNA through 24-week treatment (non-responder). Here we report viral resistance analyses for BLV monotreated participants who were non-responders or experienced virologic breakthrough (VB, 2 consecutive increases in HDV-RNA of ≥1 log10 IU/mL from nadir or 2 consecutive HDV-RNA detectable if previously undetectable) in phase II study MYR202 and phase III study MYR301. Deep-sequencing of BLV-corresponding region in HBV PreS1 and HDV HDAg gene and in vitro phenotypic testing were performed for the participant with VB (n=1) and non-responders (n=20) at baseline (BL) and Week 24 (WK24). No amino acid exchanges within the BLV-corresponding region and HDAg associated with reduced susceptibility to BLV were identified in isolates from any of the 21 participants at BL and WK24. Although variants (HBV n=1; HDV n=13) were detected at BL in some non-responders or the participant with VB, none were associated with reduced sensitivity to BLV in vitro. Furthermore, the same variant was found in virologic responders. A comprehensive phenotypic analysis demonstrated that the BLV EC50 values from 116 BL samples were similar across non-responders, partial responders (HDV RNA decline ≥1 but <2 log10 IU/mL), and responders regardless of the presence of HBV and/or HDV polymorphisms. No amino acid substitutions associated with reduced sensitivity to BLV monotherapy were detected at BL or WK24 in non-responders or the participant with VB after 24-week BLV treatment.

Metabolic profile in women with bulimia nervosa or binge-eating disorder before and after treatment: secondary analysis from the randomized PED-t trial

PurposeChaotic eating and purging behavior pose a risk to the metabolic health of women with bulimia nervosa (BN) and binge-eating disorder (BED). This study reports on one-year changes in blood markers of metabolic health and thyroid hormones in women with BN or BED attending two different treatments.MethodsThese are secondary analyses from a randomized controlled trial of 16-week group treatment of either physical exercise and dietary therapy (PED-t) or cognitive behavior therapy (CBT). Blood samples collected at pre-treatment, week eight, post-treatment, and at 6- and 12-month follow-ups were analyzed for glucose, lipids (triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-c), HDL cholesterol (HDL-c), apolipoprotein A (ApoA) and apolipoprotein B (ApoB) lipoproteins), and thyroid hormones (thyroxine (T4), thyroid stimulating hormone (TSH), and thyroperoxidase antibodies).ResultThe average levels of blood glucose, lipids and thyroid hormones were within the recommended range, but clinical levels of TC and LDL-c were detected in 32.5% and 39.1%, respectively. More women with BED compared with BN had low HDL-c, and a larger increase over time in TC and TSH. No significant differences occurred between PED-t and CBT at any measurement. Exploratory moderator analyses indicated a more unfavorable metabolic response at follow-up among treatment non-responders.ConclusionThe proportion of women with impaired lipid profiles and unfavorable lipid changes, suggests active monitoring with necessary management of the metabolic health of women with BN or BED, as recommended by metabolic health guidelines.Level of evidence: Level I: Evidence obtained from a randomized, experimental trial.Trial registration number: This trial was prospectively registered in the Norwegian Regional Committee for Medical and Health Research Ethics on December 16, 2013, with the identifier number 2013/1871, and in Clinical Trials on February 17, 2014, with the identifier number NCT02079935.

Evidence for Survival Benefit in ALS with CNM-Au8 Treatment Across Three Study Populations (P8-8.004)

Evidence for Survival Benefit in ALS with CNM-Au8 Treatment Across Three Study Populations (P8-8.004)

MANOEUVRE Study Design: A Study of GYM329 (RO7204239) in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) (S2.010)

MANOEUVRE Study Design: A Study of GYM329 (RO7204239) in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) (S2.010)

Effects of Rimegepant 75 mg on Monthly Migraine Days: a 52-Week, Open-Label Extension Study (P10-12.010)

Effects of Rimegepant 75 mg on Monthly Migraine Days: a 52-Week, Open-Label Extension Study (P10-12.010)

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

Acetyl-L-Leucine for Niemann-Pick type C: A Multinational Double-blind Randomized Placebo-controlled Crossover Study (P14-11.001)

<h3>Objective:</h3> To assess the clinical efficacy (symptomatic and long-term) of N-acetyl-L-Leucine on symptoms of ataxia, functioning, and quality of life for patients with NPC. To evaluate the safety and tolerability of N-acetyl-L-leucine at 4 g/day in patients with NPC aged ≥4 years and older. Extension Phase Only: Characterize the pharmacokinetics of N-acetyl-L-leucine in NPC patients. <h3>Background:</h3> Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded Phase IIb clinical trial. <h3>Design/Methods:</h3> This multinational double-blind randomized placebo-controlled crossover Phase III study enrolls patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites (NCT05163288). Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments. The Parent Study is followed by the 1-year Extension Phase. <h3>Results:</h3> The clinical trial has been initiated in July 2022. Twenty-one patients have been screened, 15 patients have been recruited. Approximately 53 patients will be enrolled, 46 patients will be analyzed according to the Intention to Treat (ITT). <h3>Conclusions:</h3> Given the lack of global symptomatic or disease-modifying therapies for NPC and other lysosomal diseases there is an urgent need for effective and well-tolerated drug treatments. This clinical trial was designed through a collaboration between National Regulatory Agencies, leading Clinical Experts, Patient Organizations, and the industry Sponsor. <b>Disclosure:</b> Dr. Bremova-Ertl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intrabio. The institution of Dr. Bremova-Ertl has received research support from InnoSuisse. Dr. Bremova-Ertl has received research support from Baasch-Medicus. Ms. Fields has received personal compensation for serving as an employee of IntraBio. Ms. Fields has stock in IntraBio. Ms. Fields has received intellectual property interests from a discovery or technology relating to health care. Dr. Martakis has nothing to disclose. Dr. Strupp has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for IntraBio. Dr. Strupp has received personal compensation in the range of $0-$499 for serving as a Consultant for AurisMedical. Dr. Strupp has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Strupp has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers. Dr. Strupp has stock in IntraBio.

Relationships among Postprandial Plasma Active GLP-1 and GIP Excursions, Skeletal Muscle Mass, and Body Fat Mass in Patients with Type 2 Diabetes Treated with Either Miglitol, Sitagliptin, or Their Combination: A Secondary Analysis of the MASTER Study.

We previously conducted a pilot randomized controlled trial "the MASTER study" and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.

Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study

Pegbelfermin is a polyethlene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) and stage 3 (bridging) fibrosis. The FALCON 1 study (NCT03486899) was a multicenter, randomized (1:1:1:1), double-blind, placebo-controlled study. Patients with biopsy-confirmed NASH and stage 3 fibrosis (N= 197) received weekly subcutaneous pegbelfermin (10, 20, or 40 mg) or placebo injections for 48 weeks. The week 24 primary endpoint was a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α= 0.05). Secondary/exploratory endpoints included histological and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. At week 24, the primary endpoint was met by 14% (placebo) vs 24%-31% (pegbelfermin arms); statistical significance was not reached due to lack of pegbelfermin dose response (P= .134). At weeks 24 and 48, more patients who received pegbelfermin had ≥30% relative reductions in hepatic fat fraction (magnetic resonance imaging-proton density fat fraction) vs placebo, although no differences reached statistical significance. In the pegbelfermin arms, improvements in liver fibrosis (magnetic resonance elastography and N-terminal type III collagen propeptide) and liver injury/inflammation (alanine aminotransferase, aspartate aminotransferase) were observed vs placebo. Adverse events occurred at similar frequencies across arms. No treatment-related serious adverse events were observed. The FALCON 1 study did not meet its primary endpoint; a ≥1-point decrease in fibrosis score without NASH worsening or NASH improvement without fibrosis worsening assessed via biopsy. Pegbelfermin was generally well tolerated during 48 weeks of treatment.

Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study

Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis. FALCON 2 (NCT03486912) was a randomized (1:1:1:1), double-blind, placebo-controlled study. Eligible adults had biopsy-confirmed NASH and stage 4 fibrosis. Pegbelfermin (10, 20, or 40 mg) or placebo was injected subcutaneously once weekly. The primary endpoint was 1 or more stages of improvement in the NASH Clinical Research Network fibrosis score without NASH worsening at week 48; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α= .05). Additional endpoints included histologic and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. Overall, 155 patients were randomized, and 154 patients received treatment. At week 48, 24% to 28% of the pegbelfermin arms had primary endpoint responses vs 31% of the placebo arm (P= .361). Nonalcoholic fatty liver disease activity score improvements were more frequent with pegbelfermin vs placebo and were driven primarily by reduced lobular inflammation. Numerically higher proportions of the pegbelfermin arms had liver stiffness (magnetic resonance elastography) and steatosis (magnetic resonance imaging-proton density fat fraction) improvements vs placebo; these differences were not statistically significant. Mean N-terminal type III collagen propeptide, alanine aminotransferase, and aspartate aminotransferase values were numerically lower in the 20- and/or 40-mg pegbelfermin arms compared with placebo. Serious adverse events were more frequent with pegbelfermin vs placebo, although none were treatment related. One patient (40-mg pegbelfermin) discontinued treatment because of a treatment-emergent adverse event (worsening ascites). FALCON 2 did not meet its primary endpoint of 1 or more stages of improvement in the NASH Clinical Research Network fibrosis without NASH worsening assessed via biopsy. Pegbelfermin generally was well tolerated in this advanced NASH population.

Monitoring physical activity using wearable technology in people with Achilles tendinopathy undergoing physiotherapy treatment: A feasibility prospective cohort study

ObjectivesPhysical activity modification is an important part of the management of Achilles tendinopathy. However, to our knowledge, there is a lack of evidence on objective physical activity assessment in Achilles tendinopathy. The purpose of this study is to (1) assess feasibility of using an inertial measurement unit (IMU) to monitor physical activity and IMU-derived biomechanical measures over 12-week treatment course by a physiotherapist; (2) conduct a preliminary analysis of changes in physical activity over 12-weeks. DesignA feasibility prospective cohort study SettingA community setting. ParticipantsPeople with Achilles tendinopathy who had recently commenced (≤2 sessions), or were about to commence, treatment with a physiotherapist Main outcome measuresParticipants wore a shank-mounted IMU on the affected side for one week at baseline, 6-, and 12-week follow-ups. The outcomes were pain/symptom severity, IMU-derived physical activity and biomechanical measures (stride rate, peak shank angular velocity, and peak shank acceleration). ResultsThirty participants were recruited. There was a high retention rate (97%), response rate (97%), and IMU wear compliance at each timepoint (>93%). For pain/symptom severity, a significant time effect was observed between baseline and 12-week follow-up. Physical activity and IMU-derived biomechanical measures did not change over 12 weeks. Physical activity decreased at the 6-week follow-up but only returned to the baseline level at 12-week follow-up. ConclusionsA larger-scale cohort study assessing clinical outcomes and physical activity appears feasible. Preliminary data indicate that physical activity may not change significantly over 12-weeks in people undergoing physiotherapy management for Achilles tendinopathy. Contribution of the paper•A larger-scale cohort study assessing physical activity using wearable technology over 12 weeks of treatment by a physiotherapist appears feasible.•Preliminary findings indicate physical activity may not change significantly over 12-weeks of treatment by a physiotherapist for people with Achilles tendinopathy.•Changes in pain and symptom severity after 12 weeks of treatment by a physiotherapist are not correlated with changes in physical activity level.

Efficacy of Silver Nanoparticles-Loaded Bone Cement against an MRSA Induced-Osteomyelitis in a Rat Model.

Background and Objectives: The purpose of this study was to assess the cytotoxicity and antibacterial effects of AgNP-impregnated Tetracalcium phosphate-dicalcium phosphate dihydrate (TTCP-DCPD). Materials and Methods: Using in vitro experiments, the cytotoxicity of AgNP-impregnated TTCP-DCPD against fibroblasts and osteocytes was assessed in terms of cell viability by water-soluble tetrazolium salt assay. To assess antibacterial effects, a disc diffusion test was used; osteomyelitis was induced first in vivo, by injection of methicillin-resistant Staphylococcus aureus into the tibia of rats. AgNP-impregnated TTCP-DCPD bone cement was then applied at various silver concentrations for 3 or 12 weeks. Antibacterial effects were assessed by culturing and reverse transcription-polymerase chain reaction (RT-PCR). For histological observation, the bone tissues were stained using hematoxylin and eosin. Results: Cell viability was decreased by the impregnated bone cement but did not differ according to AgNP concentration. The diameter of the growth-inhibited zone of MRSA was between 4.1 and 13.3 mm on the disks treated with AgNP, indicating antimicrobial effects. In vivo, the numbers of bacterial colonies were reduced in the 12-week treatment groups compared to the 3-week treatment groups. The groups treated with a higher (10×) dose of AgNP (G2-G5) showed a tendency of lower bacterial colony counts compared to the group without AgNP (G1). The PCR analysis results showed a tendency of decreased bacterial gene expression in the AgNP-impregnated TTCP-DCPD groups (G2-G5) compared to the group without AgNP (G1) at 3 and 12 weeks. In the H&E staining, the degree of inflammation and necrosis of the AgNP-impregnated TTCP-DCPD groups (G2-G5) showed a tendency to be lower at 3 and 12 weeks compared to the control group. Our results suggest that AgNP-impregnated TTCP-DCPD cement has antimicrobial effects. Conclusions: This study indicates that AgNP-impregnated TTCP-DCPD bone cement could be considered to treat osteomyelitis.

Effects of chronotype on antidepressant treatment and symptoms in patients with depression: a multicenter, parallel, controlled study

AimTo analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression.Methods180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed.ResultsOf the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p < 0.05). During the 12-week antidepressant treatment period, the time effect of PSQI, Shaps, MFI-20 and MEQ had interaction with different time groups (p < 0.05). During the treatment, the multiple symptom dimensions of depression were improved to different degrees, but the changing trend was not the same, and the recovery of the anhedonia was obviously delayed, in early-type patients, there are many symptoms such as loss of pleasure and sleep disorders. There was no significant effect on the remission rate of depression in different time type (p > 0.05) .ConclusionThe disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.

Glucagon-like peptide-1 analogues: a new way to quit smoking? (SKIP)—a structured summary of a study protocol for a randomized controlled study

BackgroundCigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation.MethodsThis is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence.Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition).DiscussionCombining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity.Trial registrationClinicalTrials.gov NCT03204396. Registered on June 26, 2017.

Longitudinal changes in serum adropin levels and liver fat content during liraglutide treatment in newly diagnosed patients with type 2 diabetes mellitus and metabolic dysfunction-associated fatty liver disease

AimsTo explore the effect of liraglutide treatment on serum adropin and its relationship to the liver fat content in newly diagnosed patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated fatty liver disease (MAFLD).MethodsSerum adropin level and liver fat content were assessed in patients with T2DM and MAFLD (n = 22), along with healthy controls (n = 22). Afterward, the patients received liraglutide treatment for 12 weeks. Serum adropin levels were examined by a competitive enzyme-linked immunosorbent assay. Liver fat content was quantified via magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF).ResultsWe found that patients with newly diagnosed T2DM and MAFLD had lower serum adropin levels [2.79 ± 0.47 vs. 3.27 ± 0.79 ng/mL, P < 0.05] and higher liver fat content [19.12 ± 9.46 vs. 4.67 ± 0.61%, P < 0.001], compared to healthy controls.Following 12-week liraglutide treatment, serum adropin levels increased from 2.83(2.44, 3.24) to 3.65(3.20, 3.85) ng/mL (P < 0.001), and liver fat content decreased from 18.04(11.08, 27.65) to 7.74(6.42, 13.49) % (P < 0.001) in patients with T2DM and MAFLD. Furthermore, increases in serum adropin were strongly associated with decreases in liver fat content (β = − 5.933, P < 0.001), liver enzyme and glucolipid metabolism parameters.ConclusionThe increase in serum adropin level following liraglutide treatment was strongly correlated with the reduction in liver fat content and glucolipid metabolism. Hence, adropin might be a potential marker for the beneficial effects of liraglutide on treating T2DM and MAFLD.

New insights into chronic pain management based on biopsychosocial model

The biopsychosocial model of pain dominates the scientific community’s understanding of chronic pain. Chronic pain is considered a different form of depression. In this study, pain relief was explored in chronic pain patients with different neurological disease, accompanied by comorbid symptoms, depression, and insomnia. Twenty-three chronic pain patients aged 26–79 years with comorbid symptoms were included in a prospective 12-week treatment using 10 mg vortioxetine. Different types of chronic pain were represented in this study: low back pain (13 patients), headache (four patients); neuropathic mechanism-induced pain (six patients) – spinal stenosis (two patients), radiculopathy (two patients), and trigeminal neuralgia (two patients). Efficacy of vortioxetine treatment was monitored after 1 week, 3 weeks, and 12 weeks. Visual analog scale (VAS) was used for pain intensity value. Dynamic of pain relief was assessed in accordance with comorbid depression and insomnia. Most patients with chronic pain actively reported depression (65%) and insomnia (74%). Depression was statistically rare in patients with neuropathic pain (33%) compared to patients with nociceptive pain (82%; P &lt; 0.05). Incidence of insomnia was lower, although not statistically, in patients with neuropathic mechanism-induced pain (50%) compared to patients with nociceptive pain (82%, P = 0.129). Patients younger than 65 years reported pain reduction, according to VAS, after 1 week and 3 weeks vortioxetine therapy. The mean pain relief was 1.1 cm in young patients versus 0.16 cm in patients aged &gt;65 years (P &lt; 0.01) after 1-week treatment, and it was 2.35 cm in young patients versus 1.7 cm in patients aged &gt;65 years (P &lt; 0.05) after 3-week treatment. Vortioxetine therapy was effective in different types of chronic pain, accompanied by comorbid depression and insomnia. At early stage of treatment, pain relief was lower in old patients aged &gt;65 years. Regardless of age, all patients had significant pain relief after the 12-week treatment.

Age-specific associations between serum cholesterol levels and suicidal behaviors in patients with depressive disorders: A naturalistic prospective observational cohort study.

This study investigated the effects of total cholesterol levels on prevalent, and incident suicidal behaviors according to age group (<60 vs. ≥60 years) in depressed patients. Consecutive outpatients with depressive disorders who visited the Chonnam National University Hospital between March 2012 and April 2017 were recruited. Among 1,262 patients assessed at baseline, 1,094 agreed to blood sampling for measurement of serum total cholesterol levels. Among the patients, 884 completed the 12-week acute treatment phase and were followed up at least once during the 12-month continuation treatment phase. Suicidal behaviors assessed at baseline included baseline suicidal severity; behaviors assessed at the 1-year follow-up included increased suicidal severity and fatal/non-fatal suicide attempts. Associations of baseline total cholesterol levels with the above-mentioned suicidal behaviors were analyzed using logistic regression models after adjustment for relevant covariates. Of 1,094 depressed patients, 753 (68.8%) were women. The mean (SD) age of patients was 57.0 (14.9) years. Lower total cholesterol levels (87-161 mg/dl) were associated with increased suicidal severity (Linear Wald = 4.478, p < 0.05) and fatal/non-fatal suicide attempt (Linear Wald = 7.490, p < 0.01) in patients <60 years of age. U-shaped associations between total cholesterol levels and 1-year follow-up suicidal outcomes (increased suicidal severity, Quadratic Wald = 6.299, p < 0.05; fatal/non-fatal suicide attempt, Quadratic Wald = 5.697, p < 0.05) were observed in patients ≥60 years of age. These findings suggest that differential consideration of serum total cholesterol levels according to age group may have clinical utility for predicting suicidality in patients with depressive disorders. However, because our research participants came from a single-hospital, the generalizability of our findings may be limited.

Abstract CT054: Phase 2 study to assess the efficacy, safety, and tolerability of the GDF-15 inhibitor ponsegromab in patients with cancer cachexia

Abstract Background: Cancer cachexia is a multifactorial metabolic syndrome of wasting characterized by anorexia, unintended weight loss, and decreased skeletal muscle mass, leading to progressive functional impairment, fatigue, diminished quality of life, poor response to anticancer therapy, and reduced survival. One of the biomarkers associated with cancer cachexia is cytokine growth differentiation factor 15 (GDF-15), which is secreted by tumor cells. Preliminary phase 1 data suggest that suppression of GDF-15 may lead to improvement in cachexia-related symptom burden. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signaling. The primary objective of this study (NCT05546476) is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia, and elevated circulating GDF-15 concentrations. Secondary objectives include assessing physical activity, gait, anorexia/appetite, nausea and vomiting, fatigue, and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, and immunogenicity. Trial design: This phase 2 study will enroll approximately 168 adults with non-small cell lung, pancreatic, or colorectal cancers who have cachexia and elevated GDF-15 concentrations. The study will be conducted in 2 parts. The initial 12-week treatment period will be a randomized, double-blind, placebo-controlled study wherein participants who meet eligibility criteria will be randomized 1:1:1:1 to one of 3 dose groups of ponsegromab (administered subcutaneously [SC] every 4 weeks [Q4W]) or placebo. The double-blind period will be followed by optional open-label treatment (OLT) with ponsegromab Q4W SC for up to 1 year. Upon completion of the optional OLT period, there will be a follow-up visit at Week 72. Participants who do not proceed with the optional OLT period will complete the Week 12 visit and a follow-up visit at Week 16. The primary endpoint is the mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity and gait measured by remote digital sensors; patient-reported appetite-related symptoms assessed by Functional Assessment of Anorexia-Cachexia Therapy scores; anorexia/appetite, nausea, vomiting, and fatigue evaluated according to questions from the Cancer-related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs, and electrocardiogram abnormalities. ClinicalTrials.gov identifier: NCT05546476 Citation Format: Jeffrey Crawford, Shannon Lubaczewski, Anil Tarachandani, Magdalena A. Harrington, Yan Weng, Ruolun Qiu, Susie M. Collins, Michelle I. Rossulek, James H. Revkin. Phase 2 study to assess the efficacy, safety, and tolerability of the GDF-15 inhibitor ponsegromab in patients with cancer cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT054.