NIH Clinical Center Search the Studies: Study Number, Study Title

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

Special Instructions

Currently Not Provided

Keywords

Brown Adipose Tissue;
Energy Expenditure;
Energy Metabolism;
Obesity

Recruitment Keyword(s)

None

Condition(s)

Polycystic Ovary Syndrome;
Healthy Volunteers

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:

Healthy 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.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

-Cohorts 1 and 2:

--Men and Women ages 18-40 years; All ethnicities

--BMI 18.0-40.0 kg/m2

-Cohort 3:

--Women ages 18-40 years; All ethnicities

--BMI 20.0-45.0 kg/m2

--Diagnosis on Polycystic Ovary Syndrome (PCOS) based on NIH Criteria with documentation from physician s note or laboratory reports confirming diagnosis with actual hormonal values and menstrual history. Women with a history of either partial hysterectomy or endometrial ablation can be included.

--Use monophasic oral contraceptives and with stable use for at least 3 months

-Insulin Resistance defined by either:

--HOMA-IR (a) >5.9 or (b) 2.8 < HOMA-IR < 5.9 with HDL< 51 mg/dL or

--Fasting Insulin >10.6 microU/mL

EXCLUSION CRITERIA:

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

-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), an HbA1c test >6.5%, or medications used to treat diabetes mellitus

-Elevated blood pressure that is >135/85 mmHg or currently taking antihypertensive therapy

-Hypo- or hyper-thyroid disease (history or TSH >5.0, <0.4 miU/L); L-T4 replacement

-Hypersensitivity and associated allergic reactions to mirabegron or similar drug substances or components of this medication

-Anemia, defined by Hemoglobin less than or equal to 13.7 g/dL (males) or 11.2 g/dL (females)

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

-A clinically-significant abnormal ECG, QTc interval above normal, or the current use of any QT-prolonging drug

-Use of any known adrenergic agonists, CYP3A or CYP2D6 substrates, cardiac beta- blockers, calcium channel blockers, systemic corticosteroids, monoamine oxidase inhibitors

-Use of medications related to glucose metabolism or known to cause insulin resistance (in preceding 6 months)

-Psychological conditions including (but not limited to) claustrophobia, clinical depression, bipolar disorders, or forms of mental incapacity that would be incompatible with safe and successful participation in this study

-Addiction to alcohol or substances of abuse within the last 5 years; self-reported current use of drugs or alcohol

-Irregular menstrual cycle or menstrual cycle lasting fewer than 25 days or longer than 31 days, pregnancy, childbirth within the last year, or breastfeeding in the past 12 months (for women only)

-Current use of medications/dietary supplements/alternative therapies known to alter energy metabolism

-Has participated in a clinical trial where there has been treatment with an investigational or marketed drug within 2 months prior to the start of the study

-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

-Donated blood within last 2 months

-Recent history (4 weeks) of any local or systemic infectious disease with fever or requiring antibiotics

-Raynaud s disease or intolerance of cold that would prevent the individual from spending 6 hours in a chilled room with a cooling vest

-Has elevated liver enzymes and is believed to have liver disease other than fatty liver disease

-Sickle cell anemia or other blood disorder such as hypercoagulable clotting disorders,

-Tissue conditions such as local infection or wound healing problems,

-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.

All subjects will be fully informed of the aims, nature, and risks of the study prior to giving written informed consent.


--Back to Top--

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]

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Aaron M. Cypess, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)



Ashley M. Schmitz, C.R.N.P.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 6-3940
10 CENTER DR
BETHESDA MD 20814
(301) 827-5259
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: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03049462

--Back to Top--