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Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity

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ClinicalTrials.gov Identifier: NCT03949075
Recruitment Status : Recruiting
First Posted : May 14, 2019
Last Update Posted : May 21, 2019
Sponsor:
Collaborator:
Novo Nordic
Information provided by (Responsible Party):
Nikolai Nordsborg, 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.


Condition or disease Intervention/treatment Phase
Exercise Angiotensin-Converting Enzyme Inhibitors Drug: Enalapril Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 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
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Maximal systemic oxygen uptake [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 20 minutes ]
    Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.

  2. Endurance performance [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 minute ]
    Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer

  8. Fat mass [ Time Frame: 20 minutes ]
    Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan

  9. Fat free mass [ Time Frame: 20 minutes ]
    Training-induced changes in fat free mass (kg) is determined by DXA-scan

  10. Body fat percentage [ Time Frame: 20 minutes ]
    Training-induced changes in body fat percentage (%) is determined by DXA-scan

  11. Left ventricular (LV) mass [ Time Frame: 45 minutes ]
    Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)

  12. LV end-diastolic volume [ Time Frame: 45 minutes ]
    Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI

  13. LV mean wall thickness [ Time Frame: 45 minutes ]
    Training-induced changes in LV mean wall thickness (cm) is determined by cMRI

  14. LV stroke volume [ Time Frame: 45 minutes ]
    Training-induced changes in LV stroke volume (mL) is determined by cMRI

  15. LV ejection fraction [ Time Frame: 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 [ Time Frame: 10 minutes ]
    Obtained blood samples will be analyzed for ACE activity



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • ACE I/I or ACE D/D homozygote
  • Aged 20-50 years
  • Healthy

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03949075


Contacts
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Contact: Nikolai B Nordsborg, phD +45 35321612 nbn@nexs.ku.dk
Contact: Tórur Sjúrðarson, Msc +298 519568 ts@nexs.ku.dk

Locations
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Denmark
Department of Nutrition, Exercise and Sports Recruiting
Copenhagen, Denmark, 2100
Sponsors and Collaborators
University of Copenhagen
Novo Nordic
Investigators
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Principal Investigator: Nikolai B Nordsborg, phD University of Copenhagen
Publications:
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Responsible Party: Nikolai Nordsborg, Associate Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT03949075    
Other Study ID Numbers: H-18016341
First Posted: May 14, 2019    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Fully anonymous data will be shared with other researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nikolai Nordsborg, University of Copenhagen:
Adaptation, Physiological
Genotype
Polymorphism, Genetic
Enalapril
Physiological Effects of Drugs
Additional relevant MeSH terms:
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Hypersensitivity
Immune System Diseases
Enalapril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents