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Brown Fat Activation Study

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ClinicalTrials.gov Identifier: NCT02919176
Recruitment Status : Recruiting
First Posted : September 29, 2016
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Philip Kern, University of Kentucky

Tracking Information
First Submitted Date  ICMJE August 22, 2016
First Posted Date  ICMJE September 29, 2016
Last Update Posted Date June 25, 2018
Actual Study Start Date  ICMJE September 1, 2016
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2017)
  • Change in beige adipose tissue [ Time Frame: baseline and after 10 weeks of treatment ]
    Beige adipose tissue markers will be evaluated at baseline, and after treatment with mirabegron, pioglitazone, or both drugs
  • Change in brown adipose tissue [ Time Frame: baseline and after 10 weeks of treatment ]
    Brown adipose tissue will be evaluated by PET-CT scan at baseline, and after treatment with mirabegron, pioglitazone, or both drugs
  • Change in insulin sensitivity [ Time Frame: baseline and after 10 weeks of treatment ]
    Insulin sensitivity will be assessed at baseline and after treatment with mirabegron, pioglitazone, or both drugs, using a euglycemic clamp
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: 3 years ]
Change History Complete list of historical versions of study NCT02919176 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2017)
  • Change in body mass index [ Time Frame: baseline and after 10 weeks of treatment ]
    Body mass index will be assessed at baseline and after treatment with mirabegron, pioglitazone, or both drugs
  • Change in glucose tolerance [ Time Frame: baseline and after 10 weeks of treatment ]
    Using an oral glucose tolerance test, glucose tolerance will be assessed at baseline and after treatment with mirabegron, pioglitazone, or both drugs
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
Combined treatment with both pioglitazone and mirabegron on stimulation of BAT and beige adipose [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 27, 2016)
  • The activation of BAT and beige adipose tissue on skeletal muscle lipotoxicity [ Time Frame: 3 years ]
  • The activation of BAT and beige adipose tissue by combined pioglitazone and mirabegron compared to monotherapy alone [ Time Frame: 3 years ]
 
Descriptive Information
Brief Title  ICMJE Brown Fat Activation Study
Official Title  ICMJE The Activation of Brown and Beige Fat and Role in Insulin Sensitivity
Brief Summary

This is an open lable, pilot study in which the investigator will research the effect of two FDA approved drugs, Mirabegron and Pioglitazone on fat tissue.

Pioglitazone is drug approved by the FDA for the treatment of diabetes and Mirabegron is a drug that is approved by the FDA for the treatment of overactive bladder. These drugs are not approved by the FDA for the purposes being studied in this research. Therefore, the way in which the investigator intends to use them in this study are considered investigational.

Detailed Description

The purpose of this study is to determine whether the amount and activity of brown adipose tissue (BAT) and beige adipose can be increased with the use of Mirabegron or Pioglitazone, alone or in combination.

The research procedures will be conducted at the University of Kentucky (UK) Medical Center at the Center for Clinical Translational Sciences research unit (CCTS). Study participants will need to come to the CCTS Unit for approximately 9 visits, as outlined below. Most of these visits will be less than 1 hour, but 3 visit will involve procedures and will vary in time ranging from 4 hour to 8 hours. Thus, a participant's total participation will be approximately 9 visits over the next 12 weeks.

After passing the screening phase, participants will be randomized (like the flipping of coin) at Visit 4 to one of three treatment groups and the participant will stay in their assigned treatment group during their entire participation in the study. The three groups are:

  • Group M: Mirabegron 50 mg/day
  • Group P: Pioglitazone 30 mg/day
  • Group MP: combination Mirabegron 50 mg/day and Pioglitazone 30 mg/day

Fasting requirements: Nothing to eat after 9 pm the night before a specific test or procedure.

Glucose tolerance test and fasting lab tests: This will be a standard oral glucose tolerance test using 75 g of glucose, with blood for glucose and insulin drawn at times 0, 30, 60, 90, and 120 min. This test will determine if the participants have impaired glucose tolerance, diabetes, or are normal. This fasting blood sample will be used to conduct routine blood tests that are a normal part of a physical exam, such as cholesterol, liver enzymes and electrolytes.

Based on the blood tests, the oral glucose tolerance test (OGTT), and other measurements, the investigator will determine whether a participant has impaired glucose tolerance or a normal glucose level, and whether they fit the other criteria of the study.

Body Mass Index and DXA Scan: The investigator will record the participant's weight, height, waist and hip measurements. Measurement of total body fat will be performed to determine the participant's percent body fat using dual energy X-ray absorptiometry (DXA). DXA uses very low levels of X-ray to measure the amount of fat, muscle, and bone in different body areas. Participants will be asked to lie on a table while wearing light clothing or a gown.

Positron Emission Tomography (PET) Scan: A PET scan is a type of imaging test. It uses a radioactive substance called a tracer to look for high areas of metabolic activity in the body. A PET scan is a standard test performed for certain conditions, and in this instance it is being used to see a participant's brown fat. 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) is an FDA-approved drug that is injected into the body before a PET scan, and used as a "tracer" to help light up the areas the doctors need to see. The investigators is not studying the effectiveness of this drug in this study.

To see the brown fat, the investigator will first need to make a participant cold. To do this, a participant will change into loose fitting light clothing, and then place around their midsection, a special jacket, and cold water will circulate through this jacket for 1 hr.

The jacket is then removed, and the participants are injected through a vein (IV) with the FDG tracer. The IV needle is most often inserted on the inside of the elbow. The tracer travels through the blood and collects in organs and tissues. This helps the radiologist see certain areas more clearly.

Participants will lie on a narrow table that slides into a large tunnel-shaped scanner. The PET detects signals from the tracer. A computer changes the signals into 3D pictures. The images are displayed on a monitor for the radiologist to read.

Fat biopsies: After an overnight fast, the biopsy procedures will be performed as follows: A fat sample (called a fat biopsy) will be removed by the investigator from the lower abdomen and from the thigh. The skin at the biopsy sites will be anesthetized using the local anesthetic, lidocaine, then a 1 incision will be made on the abdomen and a ½ inch incision on thigh, through the skin, and a small amount of fat tissue will be removed. The incisions will then be closed using stitches. Participants will have a total of 4 fat biopsies: Two prior to receiving study drug (at any time between visits 2-4) and two while taking the study drug (at any time between visits 6-9).

Muscle biopsy. At the time of the thigh adipose biopsy, a muscle biopsy is performed through the same skin incision. Participants will have a total of 2 muscle biopsies: 1 prior to receiving study drug (at any time between visits 2-4) and one while taking the study drug (at any time between visits 6-9).

Euglycemic clamp: Insulin sensitivity will be measured using a clamp. Participants will come to the CCTS after fasting overnight. Two intravenous plastic tubes will be inserted into veins in their arm. Participants will then be given a constant injection of glucose along with a constant injection of insulin. The glucose and insulin are balanced such that the participant's blood glucose stays constant between about 90-100 mg/dl. Blood will then be drawn from the intravenous line frequently (about every 5-10 minutes) for measurement of blood glucose and insulin. These blood measurements will continue for 4 hours; the total amount of blood that will be withdrawn will be about 100 cc (about 6 tablespoons), which is about one quarter as much as would be taken if the participant were to donate blood.

Urine Collection: Females who are capable of getting pregnant, will also be asked to give a sample of urine to test for pregnancy. If the test results positive for pregnancy, participants will not be able to participate in the study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Obese
  • Metabolic Syndrome
Intervention  ICMJE
  • Drug: Mirabegron
    Mirabegron 50 mg/day
    Other Name: MYRBETRIQ
  • Drug: Pioglitazone
    Pioglitazone 30 mg/day
    Other Name: ACTOS
  • Drug: Mirabegron and Pioglitazone
    Mirabegron 50 mg/day and Pioglitazone 30 mg/day
    Other Name: MYRBETRIQ and ACTOS
Study Arms  ICMJE
  • Active Comparator: Mirabegron
    Mirabegron 50 mg/day
    Intervention: Drug: Mirabegron
  • Active Comparator: Pioglitazone
    Pioglitazone 30 mg/day
    Intervention: Drug: Pioglitazone
  • Experimental: Mirabegron and Pioglitazone
    Combination of Mirabegron 50 mg/day and Pioglitazone 30 mg/day
    Intervention: Drug: Mirabegron and Pioglitazone
Publications * Finlin BS, Memetimin H, Confides AL, Kasza I, Zhu B, Vekaria HJ, Harfmann B, Jones KA, Johnson ZR, Westgate PM, Alexander CM, Sullivan PG, Dupont-Versteegden EE, Kern PA. Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018 Aug 9;3(15). pii: 121510. doi: 10.1172/jci.insight.121510. eCollection 2018 Aug 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 27, 2016)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • slightly abnormal blood sugar (A1C between 5.7 and 6.5 or impaired glucose tolerance)
  • Metabolic Syndrome features (hypertension, abnormal lipids, abdominal obesity)
  • Body Mass Index between 27-45
  • Ambulatory

Exclusion Criteria:

  • A history of heart disease
  • Cancer or a history of cancer within the last 5 years
  • Kidney disease
  • Currently taking steroids or anticoagulants
  • A chronic inflammatory condition such as rheumatoid arthritis or inflammatory bowel disease
  • A body mass index (BMI) greater than 45
  • Diabetes or the chronic use of any antidiabetic medications
  • Uncontrolled blood pressure, urinary retention, overactive thyroid
  • Significant swelling in hands, feet, face, arms.
  • Currently taking β-blockers
  • Daily use of NSAIDS or other anti-inflammatory drugs (eg. corticosteroids)
  • Using low-dose aspirin (Participants will need to discontinue use for 7 days prior to the biopsies)
  • Antiplatelet medication or blood thinners (examples: Aspirin, warfarin, Effient, Plavix)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Philip Kern, MD 8593235821 pake222@uky.edu
Contact: Zachary Johnson 8592180485 zrjo223@uky.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02919176
Other Study ID Numbers  ICMJE 16-0642-F1V
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Philip Kern, University of Kentucky
Study Sponsor  ICMJE Philip Kern
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Philip Kern, MD University of Kentucky
PRS Account University of Kentucky
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP