Mirabegron for Obesity

Overseen By Todd May

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must not be taking: Anticoagulants, Appetite suppressants, Corticosteroids, others

Disqualifiers: Diabetes, Pregnancy, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the medication mirabegron affects gene expression in fat tissue, specifically targeting the adrenergic Beta-3 receptor. Researchers compare these effects in two groups: individuals who are obese with insulin resistance (a condition where the body doesn't use insulin properly) and those who are not obese. Participants receive a single dose of mirabegron, with fat tissue analyzed before and after treatment. This study may suit adults who either struggle with obesity and insulin resistance or are lean with normal blood sugar levels. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking certain medications like anticoagulants, appetite-affecting drugs, systemic corticosteroids, β-adrenergic receptor blockers, or calcium channel blockers. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that mirabegron is likely to be safe for humans?

Research has shown that mirabegron is usually safe for use. Studies have found that it can help control blood sugar and improve insulin use in people who are obese and have insulin resistance. This suggests it might be safe for other uses as well. However, concerns exist. One study found that mirabegron might worsen heart and blood vessel issues, such as atherosclerosis, where arteries harden. While generally safe, these risks should be considered. Always consult a healthcare professional before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about mirabegron for obesity because it offers a unique approach compared to current treatments like lifestyle changes and medications such as orlistat or liraglutide. Mirabegron, traditionally used to treat overactive bladder, works differently by activating brown fat tissue, which can increase energy expenditure and help with weight loss. This mechanism targets the body's natural calorie-burning processes, offering a novel way to tackle obesity beyond just suppressing appetite or blocking fat absorption.

What evidence suggests that mirabegron might be an effective treatment for obesity?

Research has shown that mirabegron, a drug targeting specific receptors in the body, may aid in treating obesity. Studies have found that it can help control blood sugar levels in obese individuals, which is crucial for managing weight and related health issues. Mirabegron also increases brown fat activity, aiding in calorie burning and potentially supporting weight loss. In animal studies, mirabegron decreased body weight and fat. This trial will evaluate mirabegron in both obese and non-obese adults to assess its effectiveness in boosting metabolism and improving sugar balance. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with prediabetes and obesity (BMI 30-40) or lean individuals (BMI <27) with normal glucose levels. Participants must not be on certain heart medications, have a history of eating disorders, substance abuse, bladder issues, diabetes, heart disease or other conditions that affect study participation.

Inclusion Criteria

I am obese with prediabetes and agree to follow lifestyle guidelines during the study.

You are considered lean, meaning your body mass index is less than 27, and you have normal glucose levels.

Provision of signed and dated informed consent form

Exclusion Criteria

You are on a special diet for medical reasons like Celiac disease.

I have heart disease, such as CAD, CHF, or irregular heartbeats.

I haven't had an infection needing antibiotics or causing fever in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Pre-Dose Adipose Tissue Biopsy

Participants undergo vitals check, medical history review, indirect calorimetry, oral glucose tolerance test, adipose tissue biopsy, blood sample collection, and receive study drug for next visit

1 day

1 visit (in-person)

Post-Dose Adipose Tissue Biopsy

Participants undergo vitals check, medical history review, adipose tissue biopsy, and blood sample collection after taking the study drug

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in catecholamine sensitivity, gene expression, and protein levels

28 days (± 14 days)

What Are the Treatments Tested in This Trial?

Interventions

• Mirabegron

Trial Overview The study tests how the gene expression in fat tissue changes after a single dose of mirabegron in lean and obese participants. It's an exploratory phase 1 trial involving three visits: screening, pre-dose biopsy, and post-dose biopsy to assess the effects on ADRB3 signaling pathways.

How Is the Trial Designed?

Group I: Obese Group Experimental Treatment 1 Intervention

Single dose, 100mg oral mirabegron in Obese Insulin Resistant adults

Group II: Non-Obese Group Experimental Treatment 1 Intervention

Single dose, 100mg oral mirabegron in Non-Obese adults

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?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Citations

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

Chronic mirabegron treatment increases human brown fat ... Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7190997/

The β3-adrenergic receptor agonist mirabegron improves ... CONCLUSION. Mirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal ...

3. diabetesjournals.org diabetesjournals.org/diabetes/article/74/Supplement_1/240-OR/158485

240-OR: Mirabegron Treatment Reduces Myofibroblasts and ... Results: Mirabegron treatment reduced myofibroblasts, which are fibrotic, and reduced CXCR2, which is involved in inflammation and chemotaxis, ...

4. jci.org jci.org/articles/view/131126

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

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524259942

Beneficial Metabolic Effects of Mirabegron In Vitro and in ... In animal studies, mirabegron-treated mice had a lower body weight and adiposity. Lipid droplets in the iBAT of mirabegron-treated mice were fewer and smaller ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10649615/

Mirabegron, a Selective β3-Adrenergic Receptor Agonist, as a ... Mirabegron-treated mice, fed a high-fat diet, had lower body weight and adiposity, as well as improved glucose tolerance and insulin sensitivity ...

7. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.14779

Mirabegron: The most promising adipose tissue beiging agent Mirabegron increased UCP1 protein expression, lowered bodyweight gain, decreased adiposity, and altered the lipid droplet (LD) size in BAT to be ...

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

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

9. jci.org jci.org/articles/view/134892

The β3-adrenergic receptor agonist mirabegron improves ... Mirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans.

10. pnas.org pnas.org/doi/10.1073/pnas.1901655116

Bladder drug mirabegron exacerbates atherosclerosis ... In this study, we provide mechanistic insights on mirabegron-triggered atherosclerosis in causing potential cardiovascular and cerebrovascular ...