Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

Sponsor
University of Copenhagen (Other)
Overall Status
Completed
CT.gov ID
NCT03949075
Collaborator
(none)
52
1
2
7.5
6.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
The present study is double-blinded with regard to ACE genotype and study medication and the blinding is kept until completion of the trial
Primary Purpose:
Basic Science
Official Title:
Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity
Actual Study Start Date :
May 15, 2019
Actual Primary Completion Date :
Dec 30, 2019
Actual Study Completion Date :
Dec 30, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Enalapril treatment

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 Comparator: Placebo treatment

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

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  1. Blood volume [20 minutes]

    Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.

  2. Endurance performance [15 minutes]

    Training-induced changes in endurance performance is determined by a 2000 meter time trial on an indoor rowing ergometer

  3. 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)

  4. Mitochondrial biogenesis [60 minutes]

    Expression of complex I-V will be analyzed in order to evaluate if the applied training induced mitochondrial biogenesis.

  5. 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)

  6. 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

  7. Muscle strength [1 minute]

    Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer

  8. Fat mass [20 minutes]

    Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan

  9. Fat free mass [20 minutes]

    Training-induced changes in fat free mass (kg) is determined by DXA-scan

  10. Body fat percentage [20 minutes]

    Training-induced changes in body fat percentage (%) is determined by DXA-scan

  11. Left ventricular (LV) mass [45 minutes]

    Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)

  12. LV end-diastolic volume [45 minutes]

    Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI

  13. LV mean wall thickness [45 minutes]

    Training-induced changes in LV mean wall thickness (cm) is determined by cMRI

  14. LV stroke volume [45 minutes]

    Training-induced changes in LV stroke volume (mL) is determined by cMRI

  15. 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 (%)

Other Outcome Measures

  1. ACE activity [10 minutes]

    Obtained blood samples will be analyzed for ACE activity

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Aged 20-50 years

  • Healthy

Exclusion Criteria:

Contacts and Locations

Locations

Site City State Country Postal Code
1 Department of Nutrition, Exercise and Sports Copenhagen Denmark 2100

Sponsors and Collaborators

  • University of Copenhagen

Investigators

  • Principal Investigator: Nikolai B Nordsborg, phD, University of Copenhagen

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Nikolai Nordsborg, Associate Professor, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT03949075
Other Study ID Numbers:
  • H-18016341
First Posted:
May 14, 2019
Last Update Posted:
Nov 5, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Nikolai Nordsborg, Associate Professor, University of Copenhagen
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 5, 2020