The Physiological Responses and Adaptation of Brown Adipose Tissue to Chronic Treatment With Beta3-Adrenergic Receptor Agonists

NCT03049462 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 17005417-DK-0054
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Brown adipose tissue (BAT) is a type of fat in the body. It may prevent weight gain, improve insulin sensitivity, and reduce fatty liver. Researchers want to see if BAT helps the body burn energy. Objective: To learn more about how BAT works to burn energy. Eligibility: People ages 18-40 with a body mass index between 18 and 40 Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Dietitian interview Participants will have an overnight baseline visit. This includes: Repeats of screening tests Exercise test Scans. For one scan, a radioactive substance is injected into the arm. FSIVGIT: An IV is inserted into veins in the right and left arms. Glucose and insulin are injected in one arm. Blood glucose and insulin levels are measured from the other. Metabolic suite: Participants stay 18-19 hours in a room that measures their metabolic rate. Monitors on the body measure heart rate, movement, and temperature. Optional fat biopsy: A small piece of tissue is removed with a needle. Participants will take 2-4 pills daily for 4 weeks. All women will take the drug mirabegron. Men will be randomly get either the drug or a placebo. All participants will have a visit after 2 weeks of the pills. They will repeat the screening tests. Participants will have an overnight visit 2 weeks later. They will repeat the baseline tests. Participants will keep food and medication diaries. Participants will have a follow-up visit 2 weeks after stopping the pills. This includes heart tests.

Conditions

Polycystic Ovary Syndrome

Keywords

Brown Adipose Tissue; Energy Expenditure; Energy Metabolism; Obesity

Outcome Measures

Primary Outcomes (2)

• Cohorts 1 and 2: Change in BAT metabolic activity

  Change in brown adipose tissue (BAT) metabolic activity as measured by 18FFDG PET/CT

  4 weeks

• Cohort 3: Change in insulin sensitivity

  Change in glucose infusion rate, as measured by the hyperinsulinemic euglycemic clamp

  4 weeks

Secondary Outcomes (3)

• Identify changes in metabolic health arising from BAT activation and/or prolonged treatment with mirabegron

  4 weeks

• Cohort 3: Changes in BAT metabolic activity

  4 weeks

• Cohorts 1 and 2: Changes in insulin sensitivity

  4 weeks

Study Arms (5)

Cohort 1

EXPERIMENTAL

Females taking 100 mg of mirabegron

Drug: Mirabegron

Cohort 2A

ACTIVE COMPARATOR

Males taking 200 mg mirabegron

Drug: Mirabegron

Cohort 2B

PLACEBO COMPARATOR

Males taking placebo drug

Other: B Complex Plus Vitamin C Tablets

Cohort 3A

ACTIVE COMPARATOR

Females taking 100 mg of mirabegron

Drug: Mirabegron

Cohort 3B

PLACEBO COMPARATOR

Females taking placebo drug

Other: B Complex Plus Vitamin C Tablets

Interventions

Mirabegron DRUG

Women will take 100mg daily for 4 weeks. Men will take 200mg daily for 4 weeks. The medication is available in 50 mg tablets.

Cohort 1; Cohort 2A; Cohort 3A

B Complex Plus Vitamin C Tablets OTHER

Males will be randomized to take placebo versus active drug (mirabegron). Those taking placebo will take 4 tablets each day to mirror to active group (taking 4 tablets of 50 mg each).

Cohort 2B; Cohort 3B

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Cohort 1: (complete)
• Female
• Age 18-40 years
• BMI 18.00-40.0 kg/m\^2
• Able to understand the research and willing to sign a written informed consent document
• Cohort 2: (complete)
• Male
• Age 18-40 years
• BMI 18.00-40.0 kg/m\^2
• Able to understand the research and willing to sign a written informed consent document
• Cohort 3:
• Female
• Age 18-40 years
• BMI 25.0-50.0 kg/m\^2 or BMI \> 18.5 kg/m\^2 with PCOS diagnosis

You may not qualify if:

• Hypersensitivity and associated allergic reactions to mirabegron (or similar drug substances or components)
• Abnormal bladder function, diagnosis of bladder outlet obstruction, urinary incontinence, urgency, and urinary frequency or use of antimuscarinic medication to treat overactive bladder (OAB)
• Type 1 or Type 2 Diabetes mellitus, fasting serum glucose \>125 mg/dL, and/or an HbA1c test \>6.5%
• Hypertension, defined as blood pressure (Bullet)140/90 mmHg, based on WHO guidelines (https://www.who.int/news-room/fact-sheets/detail/hypertension)
• Hypo- or hyper-thyroid disease (TSH \>5.0, \<0.4 miU/L) that is controlled for less than one year
• Anemia, defined by hemoglobin \< 11.3 g/dL (females) or \< 13.8 g/dL (males); sickle cell anemia or other blood disorders; and/or wound healing problems
• Cardiovascular disease, cardiac arrhythmias, orthostasis, unstable vasomotor system, or renal impairment
• A clinically significant abnormal ECG and/or QTc interval above normal
• Elevated liver enzymes with probable or diagnosed liver disease (other than fatty liver disease)
• Psychological conditions such as claustrophobia, untreated clinical depression or anxiety, untreated bipolar disorders, or forms of mental incapacity that would be incompatible with safe and successful participation in this study
• Recent history in last 4 weeks of any local or systemic infectious disease with fever or requiring antibiotics
• Self-reported intolerance of cold that would prevent the individual from spending several hours in a chilled room with a cooling vest
• Current use of any drugs known to:
• have major drug-drug interactions with mirabegron
• Prolong QT interval

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA, Kapuria D, Cassimatis TM, Kelsey N, Cero C, Sater ZA, Piccinini F, Baskin AS, Leitner BP, Cai H, Millo CM, Dieckmann W, Walter M, Javitt NB, Rotman Y, Walter PJ, Ader M, Bergman RN, Herscovitch P, Chen KY, Cypess AM. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Invest. 2020 May 1;130(5):2209-2219. doi: 10.1172/JCI131126.

  PMID: 31961826 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Obesity

Interventions

mirabegron; Hydroquinones; Ascorbic Acid

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Aaron M Cypess, M.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley M Schmitz, C.R.N.P.

CONTACT

(920) 948-1186; ashley.schmitz@nih.gov

Aaron M Cypess, M.D.

CONTACT

(301) 435-9267; aaron.cypess@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 10, 2017
• Study Start: March 13, 2017
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-03-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: \>With whom - Researchers who provide a methodologically sound proposal@@@@@@\>For what types of analysis - To achieve aims in the approved proposal@@@@@@\>By what mechanism will data be made available? - Proposals should be directed to aaron.cypess@nih.gov. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)