Clinical trial NCT03949075: Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity
Official title: Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exercise
Angiotensin-Converting Enzyme Inhibitors
Keywords: Adaptation, Physiological
Genotype
Polymorphism, Genetic
Enalapril
Physiological Effects of Drugs
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 52
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* Aged 20-50 years
* Healthy

Exclusion Criteria:

-

Primary outcomes:
measure: Maximal systemic oxygen uptake
timeFrame: 20 minutes
measure: Skeletal muscle endurance
timeFrame: 5 minutes
Secondary outcomes:
measure: Blood volume
timeFrame: 20 minutes
measure: Endurance performance
timeFrame: 15 minutes
measure: Skeletal muscle oxidative capacity
timeFrame: 60 minutes
measure: Mitochondrial biogenesis
timeFrame: 60 minutes
measure: Mean arterial pressure (MAP)
timeFrame: 10 minutes
measure: Steady-state systemic oxygen uptake
timeFrame: 10 minutes
measure: Muscle strength
timeFrame: 1 minute
measure: Fat mass
timeFrame: 20 minutes
measure: Fat free mass
timeFrame: 20 minutes
measure: Body fat percentage
timeFrame: 20 minutes
measure: Left ventricular (LV) mass
timeFrame: 45 minutes
measure: LV end-diastolic volume
timeFrame: 45 minutes
measure: LV mean wall thickness
timeFrame: 45 minutes
measure: LV stroke volume
timeFrame: 45 minutes
measure: LV ejection fraction
timeFrame: 45 minutes
Other outcomes:
measure: ACE activity
timeFrame: 10 minutes
Locations:
city: Copenhagen
country: Denmark
facility: Department of Nutrition, Exercise and Sports
Study officials:
affiliation: University of Copenhagen
name: Nikolai B Nordsborg, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.