The primary objective is to assess whether the insulin-stimulated glucose uptake in quadriceps muscle can be improved through 4 weeks of supplementation of clenbuterol.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter is insulin-stimulated 18F-FDG uptake in quadriceps muscle
as assessed using radio-active labelled tracer in PET-MRI
Secondary outcome
The secondary outcome parameter is insulin-stimulated 18F-FDG uptake in BAT as
assessed using radio-active labelled tracer in PET-MRI.
Background summary
Skeletal muscle insulin resistance is a primary factor underlying an impaired
postprandial glucose clearance and a major hallmark in the development of type
2 diabetes mellitus (T2DM). As such, stimulation of skeletal muscle glucose
uptake independent of the insulin pathway could significantly contribute to a
positive disease outcome. In this context, we have recently demonstrated in
pre-clinical models that skeletal muscle glucose uptake can be mediated through
an alternative novel pathway involving β2-adrenergic receptors, through
activation of mTORC2. Thus, robust improvements in glucose homeostasis were
observed in diabetic rodents upon treatment with the selective β2-agonist
clenbuterol, also when administered at lower doses. Furthermore, we are
currently finalizing a study in young, healthy individuals which indicates that
a standard dose of clenbuterol (40 µg/day) is well-tolerated by adult humans.
During the current study, we will therefore investigate the effect of
clenbuterol supplementation on glucose homeostasis in obese subjects to
identify if targeting the β2-adrenergic-mTORC2 pathway could alleviate insulin
resistance in skeletal muscle and activate brown adipose tissue (BAT).
Study objective
The primary objective is to assess whether the insulin-stimulated glucose
uptake in quadriceps muscle can be improved through 4 weeks of supplementation
of clenbuterol.
Study design
4-week randomized, double-blinded, placebo-controlled, cross-over design with a
minimum wash-out period of 6-8 weeks.
Intervention
4-week oral supplementation with clenbuterol hydrochloride (40 ug/day) or
placebo. Capsules (20 ug) will be consumed twice daily
Study burden and risks
This study will not induce any benefits for the subjects and the major burden
will be the time investment and potential side effects of clenbuterol. In
total, the subjects will visit the University of Maastricht on 8 occasions
(excluding screening) for measurements. Performed measurements will be without
risks, but hematomas or bruises could develop upon blood sampling or muscle
biopsies taken. This risk will be minimized due to state-of-the-art techniques
and sterility measures taken. Clenbuterol or placebo supplementation will be
given for 28 days, in which subjects ingest 1 capsule (20 ug) twice daily (40
ug/day). Clenbuterol could induce adverse effects, e.g. headache, increased
heart rate/blood pressure, tremors, dizziness. However, during this study we
will use a standard dose of clenbuterol (40 ug/day), which has previously been
demonstrated to be a safe dose for human application. Furthermore, we will
apply a relatively short supplementation duration (4 weeks). To limit the
number of subjects that need to be included we decided for a cross-over design
in which every participant serves as his/her own control. Risks related to the
clamp and PET-MRI measurements are low due to clear exclusion criteria and
well-experienced researchers performing these tests. For the PET scan, a
[18F]-FDG bolus will be infused in the subject, which is a radio-active tracer
commonly used in standard medical practice. The total radiation burden in the
study per subject is ~2.7 mSv (normal background radiation in the Netherlands
is ~2.5 mSv). No contrast agents are used. MRI is a modern diagnostic tool,
which does not imply significant risks (no ionizing radiation).
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
1. Male or (postmenopausal; defined as 1 year after the last cycle) female;
2. Age between 40-75 years;
3. BMI: 25-35 kg/m2;
Exclusion criteria
1. Not meeting all inclusion criteria
2. Cardiovascular disease (determined by means of questionnaires, heart
rate/blood pressure measurements and an ECG)
3. Respiratory diseases (including asthma, bronchitis and COPD);
4. Unstable body weight (weight gain or loss > 5 kg in the last three months);
5. Intention to lose or gain body weight (e.g. with caloric restriction or
physical activity)
6. Excessive alcohol and/or drug abuse;
7. Hypokalaemia;
8. Hyperthyroidism
9. Anaemia;
10. Epilepsy;
11. Smoking;
12. Renal and/or liver insufficiency;
13. Diagnosed with type 1 or type 2 diabetes mellitus;
14. Any contra-indications to MRI scanning. These contra-indications include
patients with:
a. Electronic implants such as pacemakers, defibrillators or neurostimulators
b. Central nervous system aneurysm clip
c. Some hearing aids (such as cochlear implant) and artificial (heart) valves
which are contraindicated for MRI/MRS
d. Iron containing corpora aliena in the eye or brains
e. Claustrophobia
15. Participation in another biomedical study within 1 month before the first
study visit, possibly interfering with the study results;
16. Medication use known to hamper subject*s safety during the study
procedures; *
17. Subjects who do not want to be informed about unexpected medical findings; *
18. Subjects who do not want that their treating physician to be informed;
19. Inability to participate and/or complete the required measurements;
20. Participation in organised or structured physical exercise;
21. Any condition, disease or abnormal laboratory test result that, in the
opinion of the Investigator, would interfere with the study outcome, affect
trial participation or put the subject at undue risk;
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000731-31-NL |
| ClinicalTrials.gov | NCT04921306 |
| CCMO | NL76746.068.21 |