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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04921306
• Other study ID #: NL76746.068.21
• Status: Completed
• Phase: Phase 2
• Start date: August 16, 2022
• Est. completion date: March 1, 2024

Study information

• Verified date: May 2024
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Caucasian;

2. Male or (postmenopausal; defined as 1 year after the last cycle) female;

3. Age between 40-70 years;

4. BMI: 27-35 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 > 3 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:

1. Electronic implants such as pacemakers, defibrillators or neurostimulators

2. Central nervous system aneurysm clip

3. Some hearing aids (such as cochlear implant) and artificial (heart) valves which are contraindicated for MRI/MRS

4. Iron containing corpora aliena in the eye or brains

5. 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 (>2h per week);

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;

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• Clenbuterol Hydrochloride
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.
• Placebo
Daily ingestion of placebo capsules for a total period of 28 days with a wash-out period of at least 6-8 weeks.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University	Eurostars

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on body weight	4 weeks
Other	Lean mass	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on lean mass as assessed by Bodpod measurement	4 weeks
Other	Fat mass	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on fat mass as assessed by Bodpod measurement	4 weeks
Other	Glucose infusion rate (GIR)	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on glucose-infusion rate (GIR) during a one-step hyperinsulinemic-euglycemic clamp	4 weeks
Other	Plasma insulin concentrations	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on plasma insulin concentrations	4 weeks
Other	Plasma glucose concentrations	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on plasma glucose concentrations	4 weeks
Other	Plasma free fatty acid (FFA) concentrations	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on plasma FFA concentrations	4 weeks
Other	Plasma triacylglycerol (TAG) concentrations	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on plasma (TAG) concentrations	4 weeks
Other	Heart rate	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on heart rate as assessed by means of an automated cuff	4 weeks
Other	Blood pressure	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on blood pressure (systolic and diastolic blood pressure) as assessed by means of an automated cuff	4 weeks
Other	Energy expenditure	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on energy expenditure as measured by indirect calorimetry	4 weeks
Other	Substrate oxidation	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on substrate oxidation as measured by indirect calorimetry	4 weeks
Other	Sleeping energy expenditure	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on sleeping energy expenditure as assessed by means of whole-room indirect calorimetry	4 weeks
Other	Substrate oxidation during sleep	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on substrate oxidation during sleep as assessed by means of whole-room indirect calorimetry	4 weeks
Other	Skeletal muscle gene expression	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle gene expression of insulin signalling and beta-adrenergic pathways as determined in muscle biopsies by means of RT-qPCR	4 weeks
Other	Skeletal muscle protein expression	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle protein expression of insulin signalling and adrenergic signalling pathways as determined in muscle biopsies by means of Western blot	4 weeks
Other	Femoral artery flow mediated dilation	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on FMD as assessed by means of echo-doppler	4 weeks
Other	skeletal muscle GLUT4 translocation	Comparison between prolonged (4 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle GLUT4 translocation as assessed by means of wide-field microscopy in skeletal muscle biopsies	4 weeks
Primary	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	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