The primary objectives are: 1) to determine the effect of bile acids on glucose uptake in brown adipose tissue; 2) to determine the effect of bile acids on whole body energy expenditure and 3) to determine the effect of bile acids on skeletal muscle…
ID
Source
Brief title
Condition
- Appetite and general nutritional disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are BAT activity, which will be measured by means of
PET-CT scanning, and (non-shivering) thermogenesis, which will be measured by
means of indirect calorimetry. In addition, skeletal muscle mitochondrial
uncoupling capacity will be determined as well.
Secondary outcome
Body temperature distribution, body composition and skin perfusion.
Background summary
It has long been known that brown adipose tissue (BAT) activity is responsible
for the major part of non-shivering thermogenesis in rodents. Recently
functional BAT has been discovered in adult humans. The negative correlation
that exists was between body mass index (BMI) and BAT activity in humans,
suggests that BAT might play a significant role in the development and/or
sustainability of obesity. Therefore, it could be a target for the therapy of
obesity and it*s accompanying metabolic diseases. Recent studies have shown
that bile acids (BAs) induce D2 activity within rodent BAT and human skeletal
myocyte cultures, which promotes the conversion of the inactive thyroid hormone
thyroxine (T4) into the active 3-5-3` triiodothyronine (T3). T3, in turn,
stimulates energy expenditure in both BAT and muscle. Human evidence for this
suggestion is still limited and only a few studies have investigated the
relationship between BAs and energy expenditure (EE) in humans. It is
hypothesized that higher levels of circulating BAs will result in increased BAT
activity.
Study objective
The primary objectives are: 1) to determine the effect of bile acids on glucose
uptake in brown adipose tissue; 2) to determine the effect of bile acids on
whole body energy expenditure and 3) to determine the effect of bile acids on
skeletal muscle mitochondrial uncoupling and how this is related to
non-shivering thermogenesis.
Study design
Three PET-CT scans will be performed in each subject, in which BAT activity
will be measured, once under thermoneutral conditions after oral ingestion of
chenodeoxycholic acid (a synthetic bile acid), once under thermoneutral
conditions without ingestion of chenodeoxycholic acid, and once after
cold-exposure.
Intervention
The intervention will consist of administration of 15 milligrams of
chenodeoxycholic acid per kilogram bodyweight per 24 hours in one gift (usually
in non-obese subjects 1000 mg chenodeoxycholic acid per day).
Study burden and risks
The total absorbed radiation dose from the three PET-CT scans included in this
study, after administration of three times 50 MBq of 18F-FDG is 7.05 mSv. This
is considered as low risk.
Universiteitssingel 50
Maastricht 6200 MD
NL
Universiteitssingel 50
Maastricht 6200 MD
NL
Listed location countries
Age
Inclusion criteria
- Caucasians
- Age: 18-30 years
- Gender: male and female (females only on a specific oral contraceptive pill; microgynon 30 or levonorgestrel/ethinylestradiol)
- BMI: 18-25 kg/m2
- Good general health
Exclusion criteria
- Psychologically unstable subjects (as judged by the treating medical specialist)
- Subjects with mental retardation (as judged by the treating medical specialist)
- Subjects with severe behavior disorders (as judged by the treating medical specialist)
- Pregnancy or lactation
- The use of the following medication one month before the study is an exclusion criterium; ß-blockers, ursodeoxycholic acid, bile acid sequestrants and antacida
- Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
- Abuse of drugs and/or alcohol
- Severe diabetes which requires application of insulin or patients with diabetes-related complications
- Surgery of the gastro-intestinal tract (only appendectomy is allowed)
- Previous ERCP with papillotomy
- History of cholesystectomy or disease of the gallbladder, biliary system and/or liver
- Hyperthyroidism or hypothyroidism
- BMI > 25 kg/m2
- Participation in earlier research or medical examinations that included PET/CT scanning
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002512-27-NL |
| CCMO | NL44774.068.13 |
| Other | NTR volgt |
| OMON | NL-OMON23736 |