Brown Fat Activation Study
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 35 - 65 |
| Updated: | 6/27/2018 |
| Start Date: | September 1, 2016 |
| End Date: | December 1, 2020 |
| Contact: | Philip Kern, MD |
| Email: | pake222@uky.edu |
| Phone: | 8593235821 |
The Activation of Brown and Beige Fat and Role in Insulin Sensitivity
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.
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.
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.
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.
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)
We found this trial at
1
site
Lexington, Kentucky 40536
Principal Investigator: Philip Kern, MD
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