Alpha-Lipoic Acid + Mirabegron for Obesity

Overseen By Aaron M Cypess, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Antihypertensives, Beta-blockers, Corticosteroids, others

Disqualifiers: Diabetes, Hypertension, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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 40 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. They will log their diet, exercise, and sleep....

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot participate if you are taking certain medications like those for diabetes, hypertension, or those that affect energy metabolism. It's best to discuss your specific medications with the trial team.

Is the combination of Alpha-Lipoic Acid and Mirabegron safe for humans?

Mirabegron, used for overactive bladder, can activate brown fat and improve metabolism, but it may cause cardiovascular issues like increased heart rate and blood pressure. Long-term safety studies are needed, especially for high doses, as it may worsen conditions like atherosclerosis (a disease where plaque builds up in arteries). ^{1 2 3 4 5}

How does the drug combination of Alpha-Lipoic Acid and Mirabegron for obesity differ from other treatments?

This drug combination is unique because Mirabegron, a β3-adrenergic receptor agonist, activates brown and beige fat, increasing energy expenditure and potentially aiding weight loss, which is different from most obesity treatments that focus on reducing calorie intake or absorption. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug Alpha-Lipoic Acid for obesity?

Research shows that Alpha-Lipoic Acid (ALA) can help with weight loss and improve body mass index (BMI) in overweight or obese individuals. It also has beneficial effects on insulin sensitivity and lipid levels, which are important for managing obesity. ^{6 7 8 9 10}

Who Is on the Research Team?

Aaron M Cypess, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 with obesity (BMI between 30 and 40 kg/m2) who are generally healthy. It's not for those with severe anemia, low platelets, poor kidney function, recent pregnancy or breastfeeding, liver issues, heart rhythm problems, drug allergies including sulfa drugs, or on certain medications that affect metabolism.

Inclusion Criteria

You have a body mass index (BMI) between 30 and 40.

Exclusion Criteria

I have an irregular heartbeat or abnormal heart test results.

I am not taking medication that affects heart rhythm or interacts with specific enzymes.

Individuals with significant medical comorbidities that would render the subject s participation unsafe as assessed by the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants take mirabegron + alpha-lipoic acid or mirabegron + placebo daily for 4 weeks. Includes a 2-day clinic stay at the start and end, with outpatient visits 2 weeks after each clinic stay.

4 weeks

2 visits (in-person, 2-day stays), 1 outpatient visit

Washout

Participants undergo a washout period before crossing over to the other treatment arm.

4-12 weeks

Treatment Phase 2

Participants cross over to the other treatment arm and take the study drugs for another 4 weeks. Includes a 2-day clinic stay at the start and end, with outpatient visits 2 weeks after each clinic stay.

4 weeks

2 visits (in-person, 2-day stays), 1 outpatient visit

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Alpha-lipoic acid
• Mirabegron
• Placebo

Trial Overview The study tests if a combination of the supplement alpha-lipoic acid (ALA) and the drug mirabegron (MG), both taken orally with water at home after initial clinic stays and tests, can help process food better in obese individuals. Participants will also take MG plus a placebo during one phase to compare effects.

How Is the Trial Designed?

Group I: MG+ALA Active Control 2 Interventions

Participants take mirabegron + alpha lipoic acid daily for 4 weeks. There is testing pre- and post-treatment. Will evaluate the effects of MG+ALA on metabolic heath.

Group II: MG+Placebo Placebo Group 2 Interventions

Participants take mirabegron + placebo daily for 4 weeks. There is testing pre- and post-treatment. Will evaluate the effects of MG+Placebo on metabolic heath.

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Mirabegron, a β3-Adrenergic Receptor agonist, has been identified as a promising treatment for obesity and type 2 diabetes by stimulating the 'beiging' of white adipose tissue, which can improve metabolic health without the cardiovascular side effects seen in other treatments.

Recent studies show that mirabegron positively influences key metabolic factors such as adipokines, glucose metabolism, and lipid droplet size, making it a safer and effective option compared to traditional methods like exercise or cold exposure for inducing beiging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron: The most promising adipose tissue beiging agent. Bel, JS., Tai, TC., Khaper, N., et al.[2022]

Mirabegron, a drug used to treat overactive bladder, has been found to activate brown adipose tissue and worsen atherosclerosis-related cardiovascular disease in mice, suggesting potential risks for patients with existing heart conditions.

In studies with genetically modified mice, mirabegron increased the growth and instability of atherosclerotic plaques by raising levels of harmful cholesterol, indicating that its use may lead to serious cardiovascular issues in susceptible individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis. Sui, W., Li, H., Yang, Y., et al.[2020]

Mirabegron, a β3-adrenergic receptor agonist, has shown potential in activating brown and beige adipose tissue, which could enhance energy expenditure and aid in weight loss, but significant weight loss in obese patients has not yet been demonstrated due to short trial durations and small participant numbers.

High doses of mirabegron were found to be most effective for stimulating adipose tissue, but concerns about cardiovascular side effects necessitate further investigation into long-term safety and the potential for lower doses to achieve similar effects over extended periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirabegron, a Selective β3-Adrenergic Receptor Agonist, as a Potential Anti-Obesity Drug. Dąbrowska, AM., Dudka, J.[2023]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Effects of oral α-lipoic acid administration on body weight in overweight or obese subjects: a crossover randomized, double-blind, placebo-controlled trial. [2019]

3. England pubmed.ncbi.nlm.nih.gov

The synergic effects of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric measurements and the serum levels of VEGF, NO, sirtuin-1, and PGC1-α in obese people undergoing a weight loss diet. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Alpha-lipoic acid inhibits adipocyte differentiation by regulating pro-adipogenic transcription factors via mitogen-activated protein kinase pathways. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Mirabegron: The most promising adipose tissue beiging agent. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α1-adrenergic receptors. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Mirabegron, a Selective β3-Adrenergic Receptor Agonist, as a Potential Anti-Obesity Drug. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. [2022]