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

Tracking Information

• First Submitted Date: December 6, 2018
• First Posted Date: January 11, 2019
• Last Update Posted Date: December 1, 2022
• Actual Study Start Date: June 1, 2019
• Actual Primary Completion Date: April 23, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 8, 2019)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 28, 2022)

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

Original Secondary Outcome Measures (submitted: January 8, 2019)

• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• Skeletal muscle lipid content [ Time Frame: 2 weeks ]
  Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle lipid content as assessed in muscle biopsies.
• 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
• Skeletal muscle protein 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 protein expression of specific pathways as determined in muscle biopsies as determined by means of Western Blotting

Current Other Pre-specified Outcome Measures (submitted: November 28, 2022)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• 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.
• 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
• 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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Human Beta-2 Adrenergic Stimulation and Muscle Glucose Uptake
• Official Title: Targeting the Beta-2-adrenergic Pathway to Improve Skeletal Muscle Glucose Uptake in Healthy Humans
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Healthy

Intervention

• 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.
• Drug: Placebos
  Daily ingestion of placebo capsules for a total period of 14 days with a wash-out period of 4 weeks.

Study Arms

• 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.

  Intervention: Drug: Clenbuterol Hydrochloride
• 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.

  Intervention: Drug: Placebos

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 19, 2021): 11
• Original Estimated Enrollment (submitted: January 8, 2019): 16
• Actual Study Completion Date: April 23, 2021
• Actual Primary Completion Date: April 23, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 30 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03800290
• Other Study ID Numbers: NL67646.068.18
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Maastricht University
• Original Responsible Party: Same as current
• Current Study Sponsor: Maastricht University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Joris Hoeks, PhD; principle investigator

• PRS Account: Maastricht University
• Verification Date: July 2020