Human Beta-2 Adrenergic Stimulation and Muscle Glucose Uptake

• ClinicalTrials.gov Identifier: NCT03800290
• Recruitment Status: Completed
• First Posted: January 11, 2019
• Last Update Posted: December 1, 2022
• Sponsor: Maastricht University
• Information provided by (Responsible Party): Maastricht University

Study Description

Brief Summary:

The purpose of this study is to investigate the effect of two weeks clenbuterol/placebo supplementation on skeletal muscle glucose disposal in healthy male volunteers.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Clenbuterol Hydrochloride; Drug: Placebos	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized, double-blinded, placebo-controlled, cross-over, single-center study
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Targeting the Beta-2-adrenergic Pathway to Improve Skeletal Muscle Glucose Uptake in Healthy Humans
• Actual Study Start Date: June 1, 2019
• Actual Primary Completion Date: April 23, 2021
• Actual Study Completion Date: April 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Clenbuterol hydrochloride; Subjects will ingest clenbuterol hydrochloride capsules (20 microgram/each) twice daily (40 microgram/day) for a maximum of 14 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; Daily ingestion of clenbuterol hydrochloride capsules (40 microgram/day) for a total period of 14 days with a wash-out period of 4 weeks.
Placebo Comparator: Placebos; Subjects will ingest placebo capsules matching the clenbuterol hydrochloride capsules one time per day for a maximum of 14 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: Placebos; Daily ingestion of placebo capsules for a total period of 14 days with a wash-out period of 4 weeks.

Outcome Measures

Primary Outcome Measures :

1. Insulin-stimulated peripheral glucose disposal (Rd) [ Time Frame: 2 weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on insulin-stimulated peripheral glucose disposal (Rd) during the high-insulin infusion step during the two-step hyperinsulinemic-euglycemic clamp.

Secondary Outcome Measures :

1. Skeletal muscle GLUT4 translocation [ Time Frame: acute (4 hours) and long-term (2 weeks) ]
   Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle GLUT4 translocation as assessed by means of wide-field microscopy in skeletal muscle biopsies

Other Outcome Measures:

1. Body weight/composition [ Time Frame: 2 weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on body weight and composition as assessed by means of a Bodpod measurement.
2. Plasma substrates [ Time Frame: Acute (4 hours) and long-term (1 and 2 weeks) ]
   Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on plasma substrate concentrations, including insulin, glucose, free fatty acids and TAGs.
3. Heart rate [ Time Frame: Acute (4 hours) and long-term (1 and 2 weeks) ]
   Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on heart rate as measured by means of an automated cuff.
4. Blood pressure [ Time Frame: Acute (4 hours) and long-term (1 and 2 weeks) ]
   Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on blood pressure (systolic and diastolic) as measured by means of an automated cuff.
5. Insulin-mediated suppression of hepatic glucose production [ Time Frame: 2 weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on hepatic glucose production as assessed during the two-step hyperinsulinemic-euglycemic clamp.
6. Energy expenditure and substrate oxidation [ Time Frame: Acute (4 hours) and long-term (2 weeks) ]
   Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on energy expenditure and substrate oxidation as assessed by means of indirect calorimetry.
7. Sleeping energy expenditure and substrate oxidation [ Time Frame: 2-weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on sleeping energy expenditure and substrate oxidation as assessed by means of a metabolic chamber (indirect calorimetry).
8. Skeletal muscle glycogen [ Time Frame: 2 weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle glycogen as assessed in muscle biopsies.
9. Skeletal muscle lipid content using wide-field microscopie [ Time Frame: 2 weeks ]
   Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle lipid content as assessed in muscle biopsies by wide-field microscopie.
10. Skeletal muscle gene expression [ Time Frame: Acute (4 hours) and long-term (1 and 2 weeks) ]
    Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle gene expression of specific pathways as determined in muscle biopsies by means of RT-qPCR
11. Skeletal muscle protein expression using western blotting [ Time Frame: Acute (4 hours) and long-term (1 and 2 weeks) ]
    Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle protein expression of specific pathways as determined in muscle biopsies as determined by means of Western Blotting

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Caucasian;
2. Male sex;
3. Age: 18-30
4. BMI: 18-25 kg/m2;
5. Normal physical activity levels;

Exclusion Criteria:

1. Not meeting all inclusion criteria
2. Cardiovascular diseases (determined by means of questionnaires, heart rate/blood pressure measurements)
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. Hb < 8.4 mmol/L;
9. Epilepsy;
10. Smoking;
11. Renal and/or liver insufficiency;
12. Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results;
13. Medication use known to hamper subject's safety during the study procedures;
14. Subjects who do not want to be informed about unexpected medical findings;
15. Subjects who do not want that their treating physician to be informed;
16. Inability to participate and/or complete the required measurements;
17. Participation in organised or structured physical exercise;
18. 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;
19. Hyperthyroidism

Contacts and Locations

Locations

Netherlands

Maastricht University

Maastricht, Limburg, Netherlands, 6229ER

Sponsors and Collaborators

Maastricht University

Investigators

• Principal Investigator: Joris Hoeks, PhD; principle investigator

More Information

• Responsible Party: Maastricht University
• ClinicalTrials.gov Identifier: NCT03800290
• Other Study ID Numbers: NL67646.068.18
• First Posted: January 11, 2019
• Last Update Posted: December 1, 2022
• Last Verified: July 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maastricht University:

Beta-2 adrenergic agonist; Glucose homeostasis; Skeletal muscle; Human

Additional relevant MeSH terms:

Clenbuterol; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Sympathomimetics