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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-DK-0054

Sponsoring Institute

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

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 40 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Brown Adipose Tissue;
Energy Expenditure;
Energy Metabolism;
Obesity

Recruitment Keyword(s)

None

Condition(s)

Polycystic Ovary Syndrome

Investigational Drug(s)

mirabegron

Investigational Device(s)

None

Intervention(s)

Drug: Mirabegron
Other: B Complex Plus Vitamin C Tablets

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

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.

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Eligibility

INCLUSION CRITERIA

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Cohort 1: (complete)

1. Female

2. Age 18-40 years

3. BMI 18.00-40.0 kg/m^2

4. Able to understand the research and willing to sign a written informed consent document

Cohort 2: (complete)

1. Male

2. Age 18-40 years

3. BMI 18.00-40.0 kg/m^2

4. Able to understand the research and willing to sign a written informed consent document

Cohort 3:

1. Female

2. Age 18-40 years

3. BMI 25.0-50.0 kg/m^2 or BMI > 18.5 kg/m^2 with PCOS diagnosis

4. Diagnosis of PCOS based on NIH Criteria; defined by the presence of both clinical and/or biochemical signs of hyperandrogenism and oligo- or chronic anovulation.

5. Women of childbearing potential must agree to use a highly effective method of birth control, confirmed by the Investigator, for at least 3 months prior to the first study visit and continuing throughout the study duration.

a. Highly effective methods of birth control include:

i. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal

ii. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable

iii. Intrauterine device

iv. Intrauterine hormone-releasing system

v. Bilateral tubal occlusion

vi. Sexual abstinence, i.e., refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant)

vii. Vasectomized sexual partner (provided that partner is the sole sexual partner of the study participant and that the vasectomized partner has received medical assessment of the surgical success)

b. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for >=12 months prior to the planned date of enrollment without an alternative medical cause.

6. Insulin resistance defined by either

a. HOMA-IR score > 5.9 OR

b. HOMA-IR score > 2.8 and <5.9, with HDL <51 mg/dL OR

c. Fasting Insulin > 10.6 microU/mL

7. Able to understand the research and willing to sign a written informed consent document

EXCLUSION CRITERIA

1. Hypersensitivity and associated allergic reactions to mirabegron (or similar drug substances or components)

2. Abnormal bladder function, diagnosis of bladder outlet obstruction, urinary incontinence, urgency, and urinary frequency or use of antimuscarinic medication to treat overactive bladder (OAB)

3. Type 1 or Type 2 Diabetes mellitus, fasting serum glucose >125 mg/dL, and/or an HbA1c test >6.5%

4. Hypertension, defined as blood pressure (Bullet)140/90 mmHg, based on WHO guidelines (https://www.who.int/news-room/fact-sheets/detail/hypertension)

5. Hypo- or hyper-thyroid disease (TSH >5.0, <0.4 miU/L) that is controlled for less than one year

6. 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

7. Cardiovascular disease, cardiac arrhythmias, orthostasis, unstable vasomotor system, or renal impairment

8. A clinically significant abnormal ECG and/or QTc interval above normal

9. Elevated liver enzymes with probable or diagnosed liver disease (other than fatty liver disease)

10. 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

11. Recent history in last 4 weeks of any local or systemic infectious disease with fever or requiring antibiotics

12. Self-reported intolerance of cold that would prevent the individual from spending several hours in a chilled room with a cooling vest

13. Current use of any drugs known to:

- have major drug-drug interactions with mirabegron

- Prolong QT interval

- Alter glucose metabolism or cause insulin resistance (in last six months)

- Treat diabetes mellitus

- Treat hypertension

- Be drugs of abuse

14. Self-reported weight loss or weight gain > 5% in the preceding 6 months.

15. Pregnancy, childbirth within the last year, or breastfeeding in the past 12 months

16. Individuals who spend >70% of daily hours outdoors since the exposure to varied environmental temperatures will potentially impact the ability to influence and measure BAT activity.

17. Addiction to alcohol or substances of abuse within the last 5 years

18. Self-reported current alcohol consumption of more than 2 servings of alcohol per day

19. Self-reported current use of nicotine and/or tobacco products

20. Has participated in a clinical trial with an investigational or marketed drug within 2 months

21. Have had previous radiation exposure (X-rays, PET scans, etc.) within the last year or anticipate radiation exposure in the upcoming year - clinical and/or research - that would exceed research limits

22. Donated blood within last 2 months

23. Unwilling or unable to eat metabolic meals, as determined by dietitian consult.

24. Any other circumstances or criteria that would preclude safe participation in the study in the clinical judgment of the investigator


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Citations:

O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA, Kapuria D, Cassimatis TM, Kelsey N, Cero C, Abdul-Sater Z, 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 Jan 21. pii: 131126. doi: 10.1172/JCI131126. [Epub ahead of print]

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Contacts:

Principal Investigator

Referral Contact

For more information:

Aaron M. Cypess, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIHBC 10 - CRC BG RM 6-3950
10 CENTER DR
BETHESDA MD 20892
(301) 435-9267
aaron.cypess@nih.gov

Ashley M. Schmitz, C.R.N.P.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIHBC 10 - CRC BG RM 6-3940
10 CENTER DR
BETHESDA MD 20892
(920) 948-1186
ashley.schmitz@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT03049462

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