Mirabegron + B Complex Plus Vitamin C for Brown Adipose Tissue

Overseen By Aaron M Cypess, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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 This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how mirabegron (Myrbetriq), combined with B complex and vitamin C, affects brown adipose tissue, a type of fat that burns energy, to determine its potential for weight management and metabolic health. Researchers are particularly interested in the combination's impact on energy burning and insulin sensitivity. The trial is suitable for individuals aged 18-40 with a body mass index of 18 to 40 who wish to explore new methods for managing weight and metabolism. Participants will take pills daily for four weeks and undergo various health tests and scans to monitor changes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore its effects.

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.

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

Research has shown that mirabegron, a drug commonly used for bladder problems, can also activate brown fat in the body. This activation might help the body manage sugar and insulin more effectively. In studies, participants taking mirabegron demonstrated improved sugar and insulin processing, suggesting the drug could enhance the body's use of sugar.

Regarding safety, mirabegron is generally well-tolerated. Some studies have mentioned possible side effects, but these are usually minor. Since this trial is in an early phase, the main goal is to ensure mirabegron's safety in this new application. Researchers will closely monitor any side effects. Participants can expect careful health monitoring to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mirabegron for its potential role in activating brown adipose tissue (BAT) to help with weight management. Unlike standard treatments that typically focus on diet, exercise, or medications targeting appetite or metabolism, mirabegron works uniquely by stimulating BAT, which burns calories to produce heat. This new mechanism of action could offer a novel approach to managing obesity by increasing energy expenditure, an area where current treatments may not effectively capitalize. By targeting BAT, mirabegron opens up a new avenue that could complement existing weight management strategies.

What evidence suggests that this trial's treatments could be effective for brown adipose tissue?

Research has shown that mirabegron can increase the activity of brown fat, which helps the body burn energy. In this trial, some participants will receive mirabegron, which studies have shown boosts brown fat activity, increases resting energy expenditure, and potentially improves metabolic health without affecting body weight. Additionally, long-term use of mirabegron has been linked to better outcomes in obesity-related conditions by increasing the body's heat production. These findings suggest that mirabegron might help manage weight and improve metabolism. ^{4 6 7 8 9}

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 18-40 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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron

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.

How Is the Trial Designed?

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

Mirabegron is already approved in United States, European Union for the following indications:

Approved in United States as Myrbetriq for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

Approved in European Union as Mirabegron for:

• Overactive bladder (OAB)
• Neurogenic detrusor overactivity (NDO)

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]

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]

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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38159219/

Effects of mirabegron on brown adipose tissue and ... We found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content.

2. nature.com nature.com/articles/s41467-023-43350-8

Mirabegron displays anticancer effects by globally ... In several mouse cancer models, we provide compelling evidence that mirabegron displays broad and potent anticancer effects on various cancers.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31961826/

Chronic mirabegron treatment increases human brown fat ... RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition.

4. link.springer.com link.springer.com/article/10.1007/s00228-023-03614-0

Effects of mirabegron on brown adipose tissue and ... The study concluded that prolonged administration of mirabegron may improve obesity-related metabolic disorders by increasing BAT thermogenesis, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1043661822005801

Mirabegron-induced brown fat activation does not ... These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7190915/

Chronic mirabegron treatment increases human brown fat ... Besides effects on BAT, HDL cholesterol, and bile acids, mirabegron also produced substantial improvements in glucose and insulin metabolism.

7. pnas.org pnas.org/doi/10.1073/pnas.1901655116

Bladder drug mirabegron exacerbates atherosclerosis ... Given that mirabegron can induce brown fat activation in adult human subjects, these findings are clinically relevant. Moreover, genetic ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/213801Orig1s000PharmR.pdf

213801Orig1s000 - accessdata.fda.gov At 30 mg/kg/day, a slight to moderate decrease in lipid droplets was observed in the brown and white adipose tissue of male and female rats ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04823442

Activation of Brown Adipose Tissue Metabolism Using ... We propose that pharmacological stimulation of Beta-3 adrenergic receptor (ADBR3) at higher doses of Mirabegron may be required to elicit changes in glycemia.