Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

Exercise Clinical Trial

Official title:

Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03949075
• Other study ID #: H-18016341
• Status: Completed
• Phase: N/A
• Start date: May 15, 2019
• Est. completion date: December 30, 2019

Study information

• Verified date: November 2020
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 30, 2019
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• Aged 20-50 years

• Healthy

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Angiotensin-Converting Enzyme Inhibitors
• Exercise
• Hypersensitivity

Intervention

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

Locations

Country	Name	City	State
Denmark	Department of Nutrition, Exercise and Sports	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
University of Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ACE activity	Obtained blood samples will be analyzed for ACE activity	10 minutes
Primary	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
Primary	Skeletal muscle endurance	Training-induced changes in muscle endurance evaluated as changes in duration (sec) of a repetitive elbow-flexion exercise	5 minutes
Secondary	Blood volume	Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.	20 minutes
Secondary	Endurance performance	Training-induced changes in endurance performance is determined by a 2000 meter time trial on an indoor rowing ergometer	15 minutes
Secondary	Skeletal muscle oxidative capacity	Training-induced changes in muscle oxidative capacity is evaluated as maximal citrate synthase and 3- hydroxy-acetylCoa-dehydrogenase activity (µmol/g/min)	60 minutes
Secondary	Mitochondrial biogenesis	Expression of complex I-V will be analyzed in order to evaluate if the applied training induced mitochondrial biogenesis.	60 minutes
Secondary	Mean arterial pressure (MAP)	Training-induced changes in resting MAP (mmHg) will be estimated using this formula: MAP = diastolic pressure + 1/3 (systolic pressure - diastolic pressure)	10 minutes
Secondary	Steady-state systemic oxygen uptake	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	10 minutes
Secondary	Muscle strength	Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer	1 minute
Secondary	Fat mass	Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan	20 minutes
Secondary	Fat free mass	Training-induced changes in fat free mass (kg) is determined by DXA-scan	20 minutes
Secondary	Body fat percentage	Training-induced changes in body fat percentage (%) is determined by DXA-scan	20 minutes
Secondary	Left ventricular (LV) mass	Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)	45 minutes
Secondary	LV end-diastolic volume	Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI	45 minutes
Secondary	LV mean wall thickness	Training-induced changes in LV mean wall thickness (cm) is determined by cMRI	45 minutes
Secondary	LV stroke volume	Training-induced changes in LV stroke volume (mL) is determined by cMRI	45 minutes
Secondary	LV ejection fraction	LV stroke volume (mL) and LV end-diastolic volume (mL) will be used to measure training-induced changes in LV ejection fraction (%)	45 minutes