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Cardiovascular DiseasePhase 2ACE-REHABNCT02845063

Effect of ACE Genotype on Cardiovascular Rehabilitation

A Phase 2 study testing concentric cardiovascular training, eccentric cardiovascular training and ACE genotyping in people with Cardiovascular Disease, run by Balgrist University Hospital at 2 sites in Switzerland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The study aims to systematically investigate the interaction between training modality, ACE genotype and disease in heart patients whom complete a cardiovascular rehabilitation program. Read more about this study

Who is it for?
Ages 20 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Cardiovascular Disease
What is being tested?
concentric cardiovascular training, eccentric cardiovascular training and ACE genotyping
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
2 sitesSwitzerland
Study dates
1 May 2016to 1 Jan 2020
Phase
Phase 2
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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • relevant valvular heart disease
  • arterial hypertension (blood pressure at rest> 140/90)
  • arrhythmogenic cardiomyopathy
  • ACE inhibitor intolerance
  • contraindication for ethical reasons
  • known or suspected non-compliance with the curriculum
Show all 27Show fewer
  • smoker
  • drug or alcohol disease
  • inability of the patient to follow the study procedures (e.g. because of language problems, mental illness, dementia)
  • participation in another clinical trial within the last 30 days prior to confinement and during the study
  • other, clinically significant comorbidities (cardiac arrhythmia, renal insufficiency, hepatic dysfunction, connective tissue disease [Marfan syndrome, Ehlers-Danlos syndrome])
  • Healthy subject group inclusion criteria:
  • inconspicuous ECG under exercise (persons in whom the exercise ECG is abnormal will be referred for a cardiological evaluation recessed to the University Hospital Zurich)
  • V̇O2peak <50 ml O2 min-1 kg-1
  • Voluntary participation
  • Written informed consent of the subject to participate in the study
  • relevant valvular heart disease
  • arterial hypertension (blood pressure at rest> 140/90)
  • arrhythmogenic cardiomyopathy
  • ACE inhibitor intolerance
  • contraindication for ethical reasons
  • known or suspected non-compliance with the curriculum
  • smoker
  • drug or alcohol disease
  • inability of the patient to follow the study procedures (e.g. because of language problems, mental illness, dementia)
  • participation in another clinical trial within the last 30 days prior to confinement and during the study
  • other, clinically significant comorbidities (cardiac arrhythmia, renal insufficiency, hepatic dysfunction, connective tissue disease [Marfan syndrome, Ehlers-Danlos syndrome])

Trial locations and contacts

2 sites in 1 country.

Switzerland2 sites
  • Balgrist University Hospital

    Zurich, 8008

  • University Hospital Zurich

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: Effects of ACE Genotype on Muscular and Functional Adaptations Following a Cardiovascular Rehabilitation Program

The study aims to systematically investigate the interaction between training modality, ACE genotype and disease in heart patients whom complete a cardiovascular rehabilitation program. This is carried out with the goal to improve the benefit of cardiovascular rehabilitation for the patient by maximising adjustments in muscle structure and function with the intervention. A population of healthy individuals will be recruited who will carry out the same training program, in order to compare the training effects respective to the general population.

Read the detailed description

Pharmacological inhibition of angiotensin converting enzyme modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression. Exercise-induced muscle plasticity importantly interacts with the insertion/deletion genotype of ACE and the training modality and intensity. The aim of this study is to systematically investigate the interaction between training modality, ACE genotype and disease in heart patients whom complete a cardiovascular rehabilitation program.

There are two training modalities being used: The first modality involves cardiovascular training by an interval type of protocol that includes a high repetition number of shortening (i.e. concentric) type contractions on a softrobotic device. The second modality includes a high repetition number of lengthening (i.e. eccentric) type contractions on a softrobotic device. In both training modalities the same muscle groups are exercised over the same range of motion, with the same speed of movement, but with widely differing pedal force. Total absolute external mechanical work will be matched.

In order to assess the baseline values and the effect size of the muscle and training adjustments made, healthy male and female volunteers will be included who are matched with respect to age and sex to the patient population and undergo the same training program.

Being tested
concentric cardiovascular training, eccentric cardiovascular training, ACE genotyping
Keywords
muscle plasticity, exercise, rehabilitation, perfusion, ACE, genotype, hypertension, molecular biology
Medical subject headings
Cardiovascular Diseases, Motor Activity, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • concentric cardiovascular trainingBehavioural

    Subjects will carry out 8 weeks of cardiovascular training by an interval type of protocol that includes a high repetition number of concentric type contractions on a softrobotic device.

  • eccentric cardiovascular trainingBehavioural

    Subjects will carry out 8 weeks of cardiovascular training by an interval type of protocol that includes a high repetition number of eccentric type contractions on a softrobotic device.

  • ACE genotypingGenetic

    Subjects will be genotyped for the ACE-I/D gene polymorphism.

Study groups in NCT02845063
Study groupRoleWhat they receive
concentric cardiovascular rehabilitationExperimentalHeart patients under ACE inhibitor intake will be enrolled in the intervention 'concentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Receives: Behavioral: concentric cardiovascular training; Genetic: ACE genotyping
eccentric cardiovascular rehabilitationExperimentalHeart patients under ACE inhibitor intake will be enrolled in the intervention 'eccentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Receives: Behavioral: eccentric cardiovascular training; Genetic: ACE genotyping
concentric cardiovascular trainingActive comparatorHealthy subjects will be enrolled in the intervention 'concentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Receives: Behavioral: concentric cardiovascular training; Genetic: ACE genotyping
eccentric cardiovascular trainingActive comparatorHealthy subjects will be enrolled in the intervention 'eccentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Receives: Behavioral: eccentric cardiovascular training; Genetic: ACE genotyping

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ACE I/D genotype

    Genotype of the assessed insertion/deletion gene polymorphism of angiotensin converting enzyme ACE, i.e. ACE-II, ACE-ID or ACE-DD.

    Measured: 975 days: May 2016-January 2019

  2. Molecular muscle characteristics - mRNA

    • mRNA expression of VEGF, HIF-1a, HIF-1b, tenascin-C, Angpt1, Angpt1R, neuropilin, midkine, restin, COX4-1, COX4I-2, CPTI, LPL, LIPE, FATP, CD36 [relative expression per 28S rRNA]

    Measured: 975 days: May 2016-January 2019

  3. Molecular muscle characteristics- protein

    • Protein content of FAK, FRNK, p70S6K, mTOR, JNK, NDUFA9, SDH, UQCRC1, COX4I1, COX4I2, ATP5A1, VEGF, HIF-1a, CD31, MHC-1, MHC-2A, MHC-2X, MyoD, myogenin, CaMKII [pixel counts per actin]

    Measured: 975 days: May 2016-January 2019

  4. Molecular muscle characteristics- phosphorylation

    • Phosphorylation of proteins phospho-Y397- FAK, phospho-T421/S424-P70S6K, phospho -T183/Y185-JNK, phospho-S2448-mTOR [pixel counts per actin]

    Measured: 975 days: May 2016-January 2019

  5. Molecular muscle characteristics- ACE

    • ACE activity [fmol min-1]

    Measured: 975 days: May 2016-January 2019

  6. Cellular muscle characteristics - fiber type %

    • Distribution of type I, IIA and IIX fibers [%]

    Measured: 975 days: May 2016-January 2019

  7. Cellular muscle characteristics - fiber area %

    • Area percentage of type I, IIA and IIX fibers [% area]

    Measured: 975 days: May 2016-January 2019

  8. Cellular muscle characteristics - fiber type CSA

    • Cross sectional area of type I, IIA and IIX fibers [micrometer2]

    Measured: 975 days: May 2016-January 2019

  9. Cellular muscle characteristics - Capillary density

    • Capillary density [capillaries micrometer-2]

    Measured: 975 days: May 2016-January 2019

  10. Cellular muscle characteristics - Capillary-to-fiber ratio

    • Capillary-to-fiber ratio

    Measured: 975 days: May 2016-January 2019

  11. Functional muscle characteristics - Maximal Power

    • Maximal power during ramp test on ergometer [Watt]

    Measured: 975 days: May 2016-January 2019

  12. Functional muscle characteristics - Critical Power

    • Critical power in ramp test on ergometer [Watt]

    Measured: 975 days: May 2016-January 2019

  13. Functional muscle characteristics - Real Power

    • Real Power as estimated on the soft robotic device [Watt]

    Measured: 975 days: May 2016-January 2019

  14. Functional muscle characteristics - Reactive Power

    • Reactive Power as estimated on the soft robotic device [Watt]

    Measured: 975 days: May 2016-January 2019

  15. Functional muscle characteristics - Negative Power

    • Negative Power as estimated on the soft robotic device [Watt]

    Measured: 975 days: May 2016-January 2019

  16. Functional muscle characteristics - Maximal force

    • Maximal force during the reactive power test on the soft robotic device [Newton]

    Measured: 975 days: May 2016-January 2019

  17. Functional muscle characteristics - Maximal velocity

    • Maximal velocity during the reactive power test on the soft robotic device [m sec-1]

    Measured: 975 days: May 2016-January 2019

  18. Functional muscle characteristics - Rate of force development

    • Rate of force development as estimated during the Real Power test on the soft robotic device [meter sec-2]

    Measured: 975 days: May 2016-January 2019

  19. Muscle metabolism - muscle oxygenation ramp

    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during ramp test on ergometer [%]

    Measured: 975 days: May 2016-January 2019

  20. Muscle metabolism - muscle oxygenation robot exercise

    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during exercise on soft robot [%]

    Measured: 975 days: May 2016-January 2019

  21. Muscle metabolism - hemoglobin ramp

    • Total hemoglobin during ramp test on ergometer [%]

    Measured: 975 days: May 2016-January 2019

  22. Muscle metabolism - hemoglobin robot exercise

    • Total hemoglobin during exercise on soft robot [%]

    Measured: 975 days: May 2016-January 2019

  23. Muscle metabolism - lipid compounds

    • Concentration of lipid compounds in m. vastus lateralis muscle during exercise on soft roboter

    Measured: 975 days: May 2016-January 2019

  24. Muscle metabolism - metabolites

    • Concentration of metabolites in m. vastus lateralis muscle during exercise on soft roboter

    Measured: 975 days: May 2016-January 2019

  25. Muscle metabolism - serum glucose

    • Concentration of glucose in serum during ramp test on ergometer [mmol l-1]

    Measured: 975 days: May 2016-January 2019

  26. Muscle metabolism - serum lactate

    • Concentration of lactate in serum during ramp test on ergometer [mmol l-1]

    Measured: 975 days: May 2016-January 2019

  27. Cardiovascular function - Heart rate rest

    • Heart rate at rest [beats per minute]

    Measured: 975 days: May 2016-January 2019

  28. Cardiovascular function - Heart rate ramp

    • Heart rate in ramp test on ergometer [beats per minute]

    Measured: 975 days: May 2016-January 2019

  29. Cardiovascular function - cardiac output

    • Cardiac output [L min-1]

    Measured: 975 days: May 2016-January 2019

  30. Cardiovascular function - ejection fraction

    • Ejection fraction

    Measured: 975 days: May 2016-January 2019

  31. Cardiovascular function - Maximal oxygen uptake

    • Maximal oxygen uptake (VO2max) during ramp test on ergometer [ml O2 min-1 kg-1]

    Measured: 975 days: May 2016-January 2019

  32. Cardiovascular function - ventilation

    • Ventilation during ramp test on ergometer [L min-1]

    Measured: 975 days: May 2016-January 2019

  33. Cardiovascular function - ventilation frequency

    • Ventilation frequency ramp test on ergometer [min-1]

    Measured: 975 days: May 2016-January 2019

  34. Cardiovascular function - respiration quotient

    • Respiration quotient during ramp test on ergometer [ L O2 inspired / L CO2 expired]

    Measured: 975 days: May 2016-January 2019

  35. Cardiovascular function - endurance

    Time-to-exhaustion in constant load on ergometer [seconds]

    Measured: 975 days: May 2016-January 2019

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2016 (estimated)
  2. Study start1 May 2016
  3. Primary completion1 Jan 2019
  4. Study completion1 Jan 2020

Why it stopped: Study terminated

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02845063
Sponsor's protocol ID
W 549 ACE-REHAB
Other IDs
KEK-ZH-Nr. 2014-0319
Acronym
ACE-REHAB
Status last verified
Aug 2023
First submitted
27 Nov 2015
Last updated
16 Aug 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • van Ginkel S, Ruoss S, Valdivieso P, Degens H, Waldron S, de Haan A, Fluck M. ACE inhibition modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression. Scand J Med Sci Sports. 2016 Oct;26(10):1180-7. doi: 10.1111/sms.12572. Epub 2015 Sep 26.

    PubMed 26407530
  • van Ginkel S, Amami M, Dela F, Niederseer D, Narici MV, Niebauer J, Scheiber P, Muller E, Fluck M. Adjustments of muscle capillarity but not mitochondrial protein with skiing in the elderly. Scand J Med Sci Sports. 2015 Aug;25(4):e360-7. doi: 10.1111/sms.12324. Epub 2014 Sep 28.

    PubMed 25262765
  • Mathes S, van Ginkel SL, Vaughan D, Valdivieso P, Flück M, Gene-pharmacologial effects on exercise-induced muscle gene expression in healthy men. Anat Physiol 2015, S5.

  • van Ginkel S, de Haan A, Woerdeman J, Vanhees L, Serne E, de Koning J, Fluck M. Exercise intensity modulates capillary perfusion in correspondence with ACE I/D modulated serum angiotensin II levels. Appl Transl Genom. 2015 Mar 27;4:33-7. doi: 10.1016/j.atg.2015.03.002. eCollection 2015 Mar.

    PubMed 26937347
  • Vaughan D, Huber-Abel FA, Graber F, Hoppeler H, Fluck M. The angiotensin converting enzyme insertion/deletion polymorphism alters the response of muscle energy supply lines to exercise. Eur J Appl Physiol. 2013 Jul;113(7):1719-29. doi: 10.1007/s00421-012-2583-6. Epub 2013 Feb 9.

    PubMed 23397151
  • Fitze DP, Franchi M, Popp WL, Ruoss S, Catuogno S, Camenisch K, Lehmann D, Schmied CM, Niederseer D, Frey WO, Fluck M. Concentric and Eccentric Pedaling-Type Interval Exercise on a Soft Robot for Stable Coronary Artery Disease Patients: Toward a Personalized Protocol. JMIR Res Protoc. 2019 Mar 27;8(3):e10970. doi: 10.2196/10970.

    PubMed 30916659

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing concentric cardiovascular training, eccentric cardiovascular training and ACE genotyping in people with Cardiovascular Disease, run by Balgrist University Hospital at 2 sites in Switzerland.

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 0 inclusion and 27 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: stopped early, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Switzerland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study terminated). Results are not available in the source record.

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?

ACE I/D genotype (time frame: 975 days: May 2016-January 2019). The study lists 35 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 NCT02845063, which also lists 6 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 16 Aug 2023.

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