Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

NCT03949075 | Completed

• 1 other identifier: H-18016341
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The phenotype based on the insertion/deletion (I/D) polymorphism of the human angiotensin converting enzyme (ACE) gene has been associated with individual training response. Briefly, intervention studies have demonstrated an 11-fold greater training-induced improvement in muscular endurance for ACE I/I homozygotes compared to ACE D/D homozygotes. Importantly, the ACE I/D polymorphism causes large inter-individual differences in serum ACE activity. Because the ACE D/D genotype is characterized by high plasma ACE activity and potentially blunted endurance exercise training response, it appears likely that ACE inhibitors (ACEi) have the potential to improve the outcome of exercise training for ACE D/D homozygotes. Thus, in the present study the investigators apply a randomized double-blind placebo-controlled longitudinal design to investigate whether pharmacological inhibition of ACE activity can amplify the exercise training response in healthy humans carrying either the ACE D/D or ACE I/I genotype. The study hypothesis is that inhibition of ACE activity in healthy humans with the ACE D/D genotype will amplify the health beneficial effects of exercise training while this is not the case in ACE I/I homozygotes.

Conditions

Exercise; Angiotensin-Converting Enzyme Inhibitors

Keywords

Adaptation, Physiological; Genotype; Polymorphism, Genetic; Enalapril; Physiological Effects of Drugs

Outcome Measures

Primary Outcomes (2)

• Maximal systemic oxygen uptake

  Training-induced changes in maximal systemic oxygen uptake (L/min) is evaluated with an incremental maximal cycle protocol on a cycle ergometer

  20 minutes

• Skeletal muscle endurance

  Training-induced changes in muscle endurance evaluated as changes in duration (sec) of a repetitive elbow-flexion exercise

  5 minutes

Secondary Outcomes (15)

• Blood volume

  20 minutes

• Endurance performance

  15 minutes

• Skeletal muscle oxidative capacity

  60 minutes

• Mitochondrial biogenesis

  60 minutes

• Mean arterial pressure (MAP)

  10 minutes

Other Outcomes (1)

• ACE activity

  10 minutes

Study Arms (2)

Enalapril treatment

EXPERIMENTAL

Drug: Enalapril

Placebo treatment

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Enalapril DRUG

Participants will be assigned to daily administration of ACE inhibitors (Initially 5 mg Corodil® 'Enalapril' daily followed by up to 20 mg daily dependent on the blood pressure response) combined with an 8-week training period.

Enalapril treatment

Placebo DRUG

Participants will be assigned to daily administration of placebo (5-20 mg CaCO3) combined with an 8-week training period.

Placebo treatment

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 20-50 years
• Healthy

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (1)

Department of Nutrition, Exercise and Sports

Copenhagen, 2100, Denmark

Location

Related Publications (3)

• Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343-6. doi: 10.1172/JCI114844.

  PMID: 1976655 BACKGROUND

• Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell JD, Prasad K, Rayson M, Talmud PJ, Humphries SE. Human gene for physical performance. Nature. 1998 May 21;393(6682):221-2. doi: 10.1038/30374. No abstract available.

  PMID: 9607758 BACKGROUND

• Sjuretharson T, Bejder J, Breenfeldt Andersen A, Bonne TC, Kyhl K, Thomassen M, Prats J, Oddmarsdottir Gregersen N, Skoradal MB, Weihe P, Nordsborg NB, Mohr M. Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial. Eur J Appl Physiol. 2023 Feb;123(2):325-337. doi: 10.1007/s00421-022-05072-5. Epub 2022 Oct 22.

  PMID: 36271942 DERIVED

MeSH Terms

Conditions

Motor Activity

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Nikolai B Nordsborg, phD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The present study is double-blinded with regard to ACE genotype and study medication and the blinding is kept until completion of the trial
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 14, 2019
• Study Start: May 15, 2019
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: November 5, 2020

Record last verified: 2020-11

Locations

DK (1)