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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a combination of the study drug mirabegron (Myrbetriq) and the supplement alpha-lipoic acid might improve food processing in individuals with obesity. Participants will test whether these treatments together can enhance metabolic health. The trial involves taking the treatment at home and undergoing various tests at the clinic to monitor changes. Individuals with obesity, having a body mass index (BMI) between 30 and 40, might be suitable for this trial. Participants must follow specific guidelines, such as logging their diet and exercise, to help researchers understand the treatments' effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining mirabegron (MG) and alpha-lipoic acid (ALA) may help treat obesity. Studies have found that mirabegron is usually well-tolerated and positively affects important metabolic functions, helping the body manage sugar and fat more effectively.

Alpha-lipoic acid, a common supplement, is generally safe for most people and is known for its antioxidant properties, which protect cells from damage.

When used together, MG and ALA have not shown any serious side effects in available studies. However, as this combination is still under investigation for obesity, participants should report any side effects to the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using alpha-lipoic acid combined with mirabegron for obesity because this combination targets metabolic health differently compared to current treatments. While most obesity treatments focus on appetite suppression or fat absorption inhibition, mirabegron activates brown fat cells, which can increase energy expenditure. Meanwhile, alpha-lipoic acid is known for its antioxidant properties and potential to improve insulin sensitivity. This unique combination could offer a new approach to managing obesity by enhancing metabolic function and efficiency.

What evidence suggests that this trial's treatments could be effective for obesity?

Research shows that mirabegron (MG), a treatment in this trial, can activate fat tissue, potentially aiding in calorie burning. However, high doses may cause heart-related side effects. Studies in mice have found that combining alpha-lipoic acid (ALA) with drugs like mirabegron improves fat tissue health and reduces inflammation. In this trial, one group of participants will receive mirabegron and alpha-lipoic acid, while another group will receive mirabegron with a placebo. This combination might also enhance food processing in the body. Early findings suggest it could improve insulin sensitivity, aiding in blood sugar control. Although most information comes from animal studies, the results are promising for addressing obesity in humans. ^{3 4 6 7 8}

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05713799?aggFilters=status%3Anot%2Cphase%3A

NCT05713799 | Trial of the Combination of Alpha-Lipoic ... We hypothesize that in women and in men with obesity (BMI 30-40 kg/m2), the increases in insulin sensitivity before and after four weeks of treatment will be ...

2. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05713799/

Trial | NCT05713799 Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity ... Will evaluate the effects of MG+ALA on metabolic heath.

3. withpower.com withpower.com/trial/phase-2-insulin-resistance-1-2023-37317

Alpha-Lipoic Acid + Mirabegron for Obesity High doses of mirabegron were found to be most effective for stimulating adipose tissue, but concerns about cardiovascular side effects necessitate further ...

4. clinconnect.io clinconnect.io/trials/NCT05713799?queryID=a10de6a53771634d49ff&apos=29

Trial of the Combination of Alpha-Lipoic Acid and - ClinConnect This clinical trial is exploring whether a combination of two substances—mirabegron, which is a medication, and alpha-lipoic acid, a dietary supplement—can help ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8692380/

Combining a β3-Adrenergic Receptor Agonist with Alpha ... We report that in mice with diet-induced obesity (DIO), the combination of ALA+CL enhanced β3-AR signaling, which led to lower epiWAT inflammation, improved ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05713799

Trial of the Combination of Alpha-Lipoic Acid and ... 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 ...

7. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=000220-DK&&query=2

NIH Clinical Center: Search the Studies 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 ...

8. trial.medpath.com trial.medpath.com/clinical-trial/895f2e966ac7858d/nct05713799-phase-ii-trial-alpha-lipoic-acid-mirabegron-obesity

Trial of the Combination of Alpha-Lipoic Acid and Mirabegron ... How does the combination of mirabegron and alpha-lipoic acid compare to standard-of-care treatments for obesity in terms of efficacy and safety profiles?