Mirabegron + B Complex Plus Vitamin C for Brown Adipose Tissue

Recruiting in Palo Alto (17 mi)

Overseen by Aaron M Cypess, M.D.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Must be taking: Mirabegron

Must not be taking: Antimuscarinics, Diabetes drugs, Hypertension drugs

Disqualifiers: Diabetes, Hypertension, Cardiovascular disease, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if the drug mirabegron can increase brown fat activity in people aged 18-40 with different body types. The drug helps brown fat burn more energy, which might aid in weight loss and better sugar management.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using drugs that interact with mirabegron, prolong QT interval, alter glucose metabolism, or treat diabetes or hypertension.

What evidence supports the effectiveness of the drug Mirabegron for activating brown adipose tissue?

Research shows that Mirabegron can activate brown fat and increase the resting metabolic rate, which may help improve glucose tolerance and insulin sensitivity. It has been found to stimulate the 'browning' of white fat, potentially aiding in weight management and metabolic health. ^{1 2 3 4 5}

Is Mirabegron safe for use in humans?

Mirabegron is generally considered safe for treating overactive bladder, but it may cause cardiovascular side effects like increased heart rate and blood pressure, especially at high doses. Some studies suggest it could worsen conditions like atherosclerosis (a disease where plaque builds up in the arteries), so its long-term safety for other uses needs more research. ^{1 2 3 5 6}

How does the drug mirabegron differ from other treatments for brown adipose tissue activation?

Mirabegron is unique because it activates brown fat and increases energy expenditure by stimulating the β3-adrenergic receptors, which is different from most other treatments that do not target this specific pathway. It is primarily used for overactive bladder but has shown potential in improving metabolic health and reducing obesity-related inflammation. ^{1 2 3 4 7}

Research Team

Aaron M Cypess, M.D.

Principal Investigator

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

Eligibility Criteria

This trial is for men and women aged 18-40 with a BMI of 18-40, who use certain birth control methods. It's not for those with significant weight changes recently, bladder issues, diabetes, high blood pressure, abnormal ECGs or heart conditions, mental health disorders incompatible with the study, substance abuse history within 5 years, excessive alcohol or nicotine use, recent pregnancy or breastfeeding (women only), medication that alters metabolism or energy expenditure.

Inclusion Criteria

I have insulin resistance based on specific blood test results.

I have been using a stable form of birth control (not just condoms) for at least 3 months.

I am a woman aged 18-40 with a BMI between 25.0-50.0.

Exclusion Criteria

You have had a problem with alcohol or drugs in the past 5 years, or you are currently using drugs.

I have bladder issues like incontinence or use medication for overactive bladder.

My blood pressure is above 135/85 mmHg or I am on medication for high blood pressure.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including medical history, physical exam, blood, urine, heart tests, exercise test, scans, FSIVGIT, and metabolic suite stay

1 overnight visit

1 overnight visit (in-person)

Treatment

Participants take 2-4 pills daily for 4 weeks. Women receive mirabegron, men receive either mirabegron or placebo. Includes a visit after 2 weeks to repeat screening tests.

4 weeks

2 visits (in-person)

Follow-up

Participants have a follow-up visit 2 weeks after stopping the pills, including heart tests.

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Mirabegron (Beta3-Adrenergic Receptor Agonist)

Trial Overview Researchers are testing how brown adipose tissue (BAT) helps burn energy using mirabegron pills over four weeks. Men may receive either the drug or a placebo while all women will take mirabegron. Participants undergo various tests including scans and metabolic rate measurements in a special room. They also keep diaries of their food intake and medications.

Participant Groups

Group I: Cohort 1 Experimental Treatment 1 Intervention

Females taking 100 mg of mirabegron

Group II: Cohort 2A Active Control 1 Intervention

Males taking 200 mg mirabegron

Group III: Cohort 3A Active Control 1 Intervention

Females taking 100 mg of mirabegron

Group IV: Cohort 2B Placebo Group 1 Intervention

Males taking placebo drug

Group V: Cohort 3B Placebo Group 1 Intervention

Females taking placebo drug

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+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

Mirabegron, a β3-adrenergic receptor agonist, effectively stimulates the expression of uncoupling protein 1 (UCP1) in both mouse brown preadipocytes and 3T3-L1 cells, indicating its potential to enhance brown fat activity.

In a study with male C57BL/6J mice on a high-fat diet, mirabegron treatment resulted in lower body weight, reduced adiposity, improved glucose tolerance, and increased insulin sensitivity, suggesting it may help prevent obesity and improve metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Metabolic Effects of Mirabegron In Vitro and in High-Fat Diet-Induced Obese Mice. Hao, L., Scott, S., Abbasi, M., et al.[2020]

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]

Treatment with mirabegron was the most effective at inducing beige adipose tissue and improving insulin sensitivity and glucose homeostasis in obese insulin-resistant subjects, while pioglitazone alone or in combination did not enhance these effects.

The combination of pioglitazone and mirabegron resulted in less beiging than either treatment alone, indicating that adding pioglitazone does not provide additional benefits for inducing beige adipose tissue or increasing brown adipose tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism. Finlin, BS., Memetimin, H., Zhu, B., et al.[2022]

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]

In a study involving 14 healthy women, chronic treatment with mirabegron for 4 weeks significantly increased brown adipose tissue (BAT) metabolic activity, suggesting potential benefits for metabolic health.

The treatment also improved insulin sensitivity and elevated beneficial lipoprotein levels, indicating that mirabegron may be a promising option for addressing obesity-related metabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. O'Mara, AE., Johnson, JW., Linderman, JD., et al.[2021]

In a study involving diet-induced obese mice, mirabegron treatment for 2 weeks significantly increased energy expenditure and reduced body fat, indicating its potential effectiveness in improving metabolic health.

Mirabegron also lowered levels of inflammatory markers and circulating fatty acids, suggesting it may help reduce inflammation and improve metabolic parameters associated with obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue. Peres Valgas da Silva, C., Calmasini, F., Alexandre, EC., et al.[2022]

References

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

Beneficial Metabolic Effects of Mirabegron In Vitro and in High-Fat Diet-Induced Obese Mice. [2020]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Pioglitazone does not synergize with mirabegron to increase beige fat or further improve glucose metabolism. [2022]

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

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

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

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue. [2022]