ExerciseNCT03949075
Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity
A study testing Enalapril in people with Exercise and Angiotensin-Converting Enzyme Inhibitors, run by University of Copenhagen at 1 site in Denmark.
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… Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Exercise, Angiotensin-Converting Enzyme Inhibitors
- What is being tested?
- Enalapril
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteDenmark
- Study dates
- 15 May 2019to 30 Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 20-50 years
- Healthy
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Exercise, Angiotensin-Converting Enzyme Inhibitors
- Being tested
- Enalapril, Placebo
- Keywords
- Adaptation, Physiological, Genotype, Polymorphism, Genetic, Enalapril, Physiological Effects of Drugs
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnalaprilDrug
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.
PlaceboDrug
Participants will be assigned to daily administration of placebo (5-20 mg CaCO3) combined with an 8-week training period.
| Study group | Role | What they receive |
|---|---|---|
| Enalapril treatment | Experimental | Not described Receives: Drug: Enalapril |
| Placebo treatment | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 20 minutes
Skeletal muscle endurance
Training-induced changes in muscle endurance evaluated as changes in duration (sec) of a repetitive elbow-flexion exercise
Measured: 5 minutes
Secondary outcomes (15)
Blood volume
Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.
Measured: 20 minutes
Endurance performance
Training-induced changes in endurance performance is determined by a 2000 meter time trial on an indoor rowing ergometer
Measured: 15 minutes
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)
Measured: 60 minutes
Mitochondrial biogenesis
Expression of complex I-V will be analyzed in order to evaluate if the applied training induced mitochondrial biogenesis.
Measured: 60 minutes
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)
Measured: 10 minutes
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
Measured: 10 minutes
Muscle strength
Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer
Measured: 1 minute
Fat mass
Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan
Measured: 20 minutes
Fat free mass
Training-induced changes in fat free mass (kg) is determined by DXA-scan
Measured: 20 minutes
Body fat percentage
Training-induced changes in body fat percentage (%) is determined by DXA-scan
Measured: 20 minutes
Left ventricular (LV) mass
Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)
Measured: 45 minutes
LV end-diastolic volume
Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI
Measured: 45 minutes
LV mean wall thickness
Training-induced changes in LV mean wall thickness (cm) is determined by cMRI
Measured: 45 minutes
LV stroke volume
Training-induced changes in LV stroke volume (mL) is determined by cMRI
Measured: 45 minutes
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 (%)
Measured: 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start15 May 2019
- Primary completion30 Dec 2019
- Study completion30 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ExerciseStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nikolai Nordsborg, University of Copenhagen
- Investigators
- Nikolai B Nordsborg, phD, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03949075
- Sponsor's protocol ID
- H-18016341
- Status last verified
- Nov 2020
- First submitted
- 9 May 2019
- Last updated
- 5 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Fully anonymous data will be shared with other researchers.
Publications
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.
PubMed 1976655Montgomery 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.
PubMed 9607758Sjuretharson 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.
PubMed 36271942
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Angiotensin Converting Enzyme Activity on Exercise Training Sensitivity
- ClinicalTrials.gov ID
- NCT03949075
- Acronym / sponsor ID
- H-18016341
- Conditions
- Exercise, Angiotensin-Converting Enzyme Inhibitors
- Keywords
- Adaptation, Physiological, Genotype, Polymorphism, Genetic, Enalapril, Physiological Effects of Drugs
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Study start
- 15 May 2019 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 14 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enalapril treatment | Experimental | Drug: Enalapril |
| Placebo treatment | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Aged 20-50 years
- Healthy
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnalaprilParticipants 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. | Drug | Enalapril treatment |
| PlaceboParticipants will be assigned to daily administration of placebo (5-20 mg CaCO3) combined with an 8-week training period. | Drug | Placebo treatment |
Primary outcome
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
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
15 secondary outcomes
Blood volume
Time frame: 20 minutes
Endurance performance
Time frame: 15 minutes
Skeletal muscle oxidative capacity
Time frame: 60 minutes
Mitochondrial biogenesis
Time frame: 60 minutes
Mean arterial pressure (MAP)
Time frame: 10 minutes
Steady-state systemic oxygen uptake
Time frame: 10 minutes
Muscle strength
Time frame: 1 minute
Fat mass
Time frame: 20 minutes
Fat free mass
Time frame: 20 minutes
Body fat percentage
Time frame: 20 minutes
Left ventricular (LV) mass
Time frame: 45 minutes
LV end-diastolic volume
Time frame: 45 minutes
LV mean wall thickness
Time frame: 45 minutes
LV stroke volume
Time frame: 45 minutes
LV ejection fraction
Time frame: 45 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2020.
- Background: PubMed 1976655Rigat 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.
- Background: PubMed 9607758Montgomery 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.
- Derived from this study: PubMed 36271942Sjuretharson 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.
- Individual participant dataSharing planned: Undecided. Fully anonymous data will be shared with other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nikolai B Nordsborg, phD principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Enalapril in people with Exercise and Angiotensin-Converting Enzyme Inhibitors, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal systemic oxygen uptake (time frame: 20 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03949075, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2020.