NCT05713799

Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity

Phase II Trial of the Combination of Alpha-lipoic Acid and Mirabegron in Women and in Men With Obesity

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

Background: Obesity and related illnesses cause at least 2.8 million deaths each year worldwide. Few treatments exist for obesity that are safe and widely available. A study drug (mirabegron \[MG\]) combined with a supplement (alpha-lipoic acid \[ALA\]) may help. Objective: To learn how MG and ALA can help the body process food. Eligibility: People aged 18 to 65 years with a body mass index between 30 and 45 kg/m2. Design: Participants will be screened. They will have a physical exam. They will have blood and urine tests and a test of their heart function. They will speak with a dietician. The study has two phases. Each phase begins with a 2-day stay in the clinic; then the participant will take the study drugs at home for about 4 weeks, followed by another 2-day stay in the clinic. They will also have outpatient visits about 2 weeks after each clinic stay. During the clinic stays, participants will undergo many tests: They will have a plastic tube (catheter) inserted into a vein in each arm. These will be used to draw blood and to infuse glucose (sugar) and insulin. They will have imaging scans. They will have a clear hard plastic shield placed over their head to measure oxygen and carbon dioxide as they breathe. Participants will take the study drugs at home. Both MG and ALA are taken by mouth with water. During one phase, participants will take MG plus a placebo. A placebo looks like the study drug but doesn t contain medicine....

Detailed description

Study Description: This is a single site, Phase II single-blinded, randomized placebo control crossover pilot study. This study aims to explore the effect of adding alphalipoic acid (ALA) to mirabegron (MG) on glucose metabolism and lipolysis rate. Participant target enrollment of 48 total otherwise healthy women (n=24) and men (n=24) with obesity who will be given one of two dosing assignments: MG 50 mg/d and ALA 2400 mg/d or MG 50 mg/d + placebo over 4 weeks followed by a 4-26-week washout period, after which time participant cross over to the opposite dosing assignment. Participants will undergo metabolic testing, safety assessments, and imaging before and after each of the two arms are completed. Women and men will be studied separately using the same protocol. We hypothesize that in women and in men with obesity (BMI 30-45 kg/m\^2), the increases in insulin sensitivity and beta3-AR agonist-induced lipolysis before and after four weeks of taking the dosing assignment will be higher in participants taking the combination MG 50 mg/d and ALA 2400 mg/d compared to taking MG 50 mg/d +placebo. -Of note, based on our preliminary data and reports in the literature, a key secondary hypothesis is that in women and in men with obesity (BMI 30-45 kg/m\^2), the increases in beta3-AR agonist-induced lipolysis before and after four weeks of dosing will be higher in participants taking the combination MG 50 mg/d and ALA 2400 mg/d compared to taking MG 50 mg/d + placebo. Objectives: * Primary objective: To compare the change in insulin sensitivity before and after four weeks of taking the combination of the MG 50 mg/d and ALA 2400 mg/d) compared to taking MG 50 mg/d + placebo. * Secondary objectives: * Assess the rate of steady-state whole-body lipolysis measured as the rate of isotope appearance (Ra) of \[2H5\] glycerol before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo. * Determine serum lipids levels before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo * To determine the safety and tolerability of the combination of mirabegron (MG) at a dose of 50mg/d with alpha-lipoic acid (ALA) at a dose of 2400 mg/d. * Assess adipose tissue inflammation and serum inflammatory markers before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo. Endpoints: * Primary Endpoint: the changes in the Insulin Sensitivity Index (SI) obtained from the FSIGT. * Secondary Endpoints: * Maximum observed plasma concentration of ALA and mirabegron (Cmax), time to maximum observed plasma concentration of ALA (Tmax), and area under the concentration-time curve from 0 to 6 hours post-dose. * Changes in adipose tissue local inflammation before and on dosing assignments will be compared between the two study arms. * Changes in serum cytokines before and after the dosing assignments will be compared between the two study arms. * Changes in plasma lipids before and after dosing assignments will be compared between the two study arms. * The rate of steady-state whole-body lipolysis measured as the rate of isotope appearance (Ra) of \[2H5\] glycerol before and on dosing assignments will be compared between the two study arms. * Tertiary/Exploratory Endpoints: * Assess the resting metabolic rate (RMR) before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo * Assess body composition before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo * Assess changes in glucose turnover using labeled glucose and water before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d + placebo * Assess liver inflammation and fat content by FibroScan(R) before and on MG 50 mg/d and ALA 2400 mg/d compared to MG 50 mg/d+ placebo * Determine serum levels of metabolic molecules and hormones before and on MG 50 mg/d and ALA 2400 g/d compared to MG 50 mg/d + placebo

Conditions

• Insulin Resistance
• Obesity

Interventions

Type	Name	Description
DRUG	Alpha-lipoic acid	ALA (2.4g) is in a capsule taken twice per day, once in the morning and once in the evening.
DRUG	Mirabegron	Mirabegron (50mg) is a yellow pill taken once per day in the morning.
DRUG	Placebo	Placebo will be visibly similar to ALA capsules. They are off-white, clear vegetable-based capsules containing an inert microcrystalline cellulose powder.

Timeline

• Start date: 2026-04-22
• Primary completion: 2030-03-01
• Completion: 2030-03-01
• First posted: 2023-02-06
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study