Human Beta-2 Adrenergic Stimulation and Muscle Glucose Uptake

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Clenbuterol Hydrochloride; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin-stimulated peripheral glucose disposal (Rd)	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.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle GLUT4 translocation	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	acute (4 hours) and long-term (2 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight/composition	Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on body weight and composition as assessed by means of a Bodpod measurement.	2 weeks
Plasma substrates	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.	Acute (4 hours) and long-term (1 and 2 weeks)
Heart rate	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.	Acute (4 hours) and long-term (1 and 2 weeks)
Blood pressure	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.	Acute (4 hours) and long-term (1 and 2 weeks)
Insulin-mediated suppression of hepatic glucose production	Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on hepatic glucose production as assessed during the two-step hyperinsulinemic-euglycemic clamp.	2 weeks
Energy expenditure and substrate oxidation	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.	Acute (4 hours) and long-term (2 weeks)
Sleeping energy expenditure and substrate oxidation	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).	2-weeks
Skeletal muscle glycogen	Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle glycogen as assessed in muscle biopsies.	2 weeks
Skeletal muscle lipid content using wide-field microscopie	Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle lipid content as assessed in muscle biopsies by wide-field microscopie.	2 weeks
Skeletal muscle gene expression	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	Acute (4 hours) and long-term (1 and 2 weeks)
Skeletal muscle protein expression using western blotting	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	Acute (4 hours) and long-term (1 and 2 weeks)

Collaborators and Investigators

• Sponsor: Maastricht University
• Investigators: Principal Investigator: Joris Hoeks, PhD, principle investigator

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ACTUAL): April 23, 2021
• Study Completion (ACTUAL): April 23, 2021

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (ACTUAL): January 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Human; Skeletal muscle; Glucose homeostasis; Beta-2 adrenergic agonist
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Clenbuterol
• Other Study ID Numbers: NL67646.068.18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No