Obese Human Beta-2-adrenergic Stimulation and Muscle Glucose Uptake

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of four weeks clenbuterol/placebo supplementation on skeletal muscle glucose disposal in overweight/obese male and (postmenopausal) female volunteers.

Official Title
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Targeting the Beta-2-adrenergic Pathway to Improve Skeletal Muscle Glucose Uptake in Obese Humans

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Clenbuterol Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian; Male or (postmenopausal; defined as 1 year after the last cycle) female; Age between 40-70 years; BMI: 27-35 kg/m2; Exclusion Criteria: Not meeting all inclusion criteria Cardiovascular disease (determined by means of questionnaires, heart rate/blood pressure measurements and an ECG) Respiratory diseases (including asthma, bronchitis and COPD); Unstable body weight (weight gain or loss > 3 kg in the last three months); Intention to lose or gain body weight (e.g. with caloric restriction or physical activity) Excessive alcohol and/or drug abuse; Hypokalaemia; Hyperthyroidism Anaemia; Epilepsy; Smoking; Renal and/or liver insufficiency; Diagnosed with type 1 or type 2 diabetes mellitus; Any contra-indications to MRI scanning. These contra-indications include patients with: Electronic implants such as pacemakers, defibrillators or neurostimulators Central nervous system aneurysm clip Some hearing aids (such as cochlear implant) and artificial (heart) valves which are contraindicated for MRI/MRS Iron containing corpora aliena in the eye or brains Claustrophobia Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results; Medication use known to hamper subject's safety during the study procedures; Subjects who do not want to be informed about unexpected medical findings; Subjects who do not want that their treating physician to be informed; Inability to participate and/or complete the required measurements; Participation in organised or structured physical exercise (>2h per week); 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;

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clenbuterol hydrochloride<br>Subjects will ingest clenbuterol hydrochloride capsules (20 microgram/each) twice daily (40 microgram/day) for a maximum of 28 days. Subjects that received the clenbuterol hydrochloride capsules (at random) in the first study period will receive the placebo capsules during the second study period. | Drug: Clenbuterol Hydrochloride<br>* Daily ingestion of clenbuterol hydrochloride capsules (40 microgram/day) for a total period of 28 days with a wash-out period of at least 6-8 weeks.<br>|
| Placebo Comparator: Placebo<br>Subjects will ingest placebo capsules matching the clenbuterol hydrochloride capsules one time per day for a maximum of 28 days. Subjects that received the placebo capsules (at random) in the first study period will receive the clenbuterol hydrochloride capsules during the second study period. | Drug: Placebo<br>* Daily ingestion of placebo capsules for a total period of 28 days with a wash-out period of at least 6-8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin-stimulated fluorodeoxyglucose (18F-FDG) uptake in quadriceps muscle. | Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on insulin-stimulated 18F-FDG uptake in quadriceps muscle as assessed using radio-active labelled tracer (18F-FDG) in positron emission tomogaphy magnetic resonance imaging (PET-MRI). | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin-stimulated 18F-FDG uptake in BAT | Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on insulin-stimulated 18F-FDG uptake in BAT as assessed using radio-active labelled tracer (18F-FDG) in PET-MRI. | 4 weeks |