Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

Not Applicable

Completed

• Conditions: Angiotensin-Converting Enzyme Inhibitors; Exercise
• Interventions: Drug: Placebo; Drug: Enalapril

• Registration Number: NCT03949075
• Lead Sponsor: University of Copenhagen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-09
• Study First Submitted QC: 2019-05-11
• Study First Posted: 2019-05-14
• Study Start: 2019-05-15
• Primary Completion: 2019-12-30
• Study Completion: 2019-12-30
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• Aged 20-50 years
• Healthy

Exclusion Criteria

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo treatment	Placebo	-
Enalapril treatment	Enalapril	-

Primary Outcome Measures

Name	Time	Method
Maximal systemic oxygen uptake	20 minutes	Training-induced changes in maximal systemic oxygen uptake (L/min) is evaluated with an incremental maximal cycle protocol on a cycle ergometer
Skeletal muscle endurance	5 minutes	Training-induced changes in muscle endurance evaluated as changes in duration (sec) of a repetitive elbow-flexion exercise

Secondary Outcome Measures

Name	Time	Method
Blood volume	20 minutes	Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.
Steady-state systemic oxygen uptake	10 minutes	Training-induced changes in steady-state systemic oxygen uptake (mL/min) is determined by indirect calorimetry during a submaximal cycle protocol on a cycle ergometer
Muscle strength	1 minute	Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer
Left ventricular (LV) mass	45 minutes	Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)
Skeletal muscle oxidative capacity	60 minutes	Training-induced changes in muscle oxidative capacity is evaluated as maximal citrate synthase and 3- hydroxy-acetylCoa-dehydrogenase activity (µmol/g/min)
Mitochondrial biogenesis	60 minutes	Expression of complex I-V will be analyzed in order to evaluate if the applied training induced mitochondrial biogenesis.
Fat free mass	20 minutes	Training-induced changes in fat free mass (kg) is determined by DXA-scan
Body fat percentage	20 minutes	Training-induced changes in body fat percentage (%) is determined by DXA-scan
LV end-diastolic volume	45 minutes	Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI
Mean arterial pressure (MAP)	10 minutes	Training-induced changes in resting MAP (mmHg) will be estimated using this formula: MAP = diastolic pressure + 1/3 (systolic pressure - diastolic pressure)
Fat mass	20 minutes	Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan
Endurance performance	15 minutes	Training-induced changes in endurance performance is determined by a 2000 meter time trial on an indoor rowing ergometer
LV mean wall thickness	45 minutes	Training-induced changes in LV mean wall thickness (cm) is determined by cMRI
LV stroke volume	45 minutes	Training-induced changes in LV stroke volume (mL) is determined by cMRI
LV ejection fraction	45 minutes	LV stroke volume (mL) and LV end-diastolic volume (mL) will be used to measure training-induced changes in LV ejection fraction (%)

Trial Locations

Locations (1)

Department of Nutrition, Exercise and Sports; 🇩🇰 Copenhagen, Denmark