Effect of ACE Genotype on Cardiovascular Rehabilitation

NCT ID: NCT02845063

Last Updated: 2023-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-01

Study Completion Date

2020-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiovascular Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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concentric cardiovascular rehabilitation

Heart patients under ACE inhibitor intake will be enrolled in the intervention 'concentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'

Group Type EXPERIMENTAL

concentric cardiovascular training

Intervention Type BEHAVIORAL

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.

ACE genotyping

Intervention Type GENETIC

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

eccentric cardiovascular rehabilitation

Heart patients under ACE inhibitor intake will be enrolled in the intervention 'eccentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'

Group Type EXPERIMENTAL

eccentric cardiovascular training

Intervention Type BEHAVIORAL

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 genotyping

Intervention Type GENETIC

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

concentric cardiovascular training

Healthy subjects will be enrolled in the intervention 'concentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'

Group Type ACTIVE_COMPARATOR

concentric cardiovascular training

Intervention Type BEHAVIORAL

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.

ACE genotyping

Intervention Type GENETIC

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

eccentric cardiovascular training

Healthy subjects will be enrolled in the intervention 'eccentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'

Group Type ACTIVE_COMPARATOR

eccentric cardiovascular training

Intervention Type BEHAVIORAL

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 genotyping

Intervention Type GENETIC

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

Interventions

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concentric cardiovascular training

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.

Intervention Type BEHAVIORAL

eccentric cardiovascular training

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.

Intervention Type BEHAVIORAL

ACE genotyping

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

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* stable coronary heart patients/heart patients without ischemia
* Left ventricular ejection fraction \> 50%
* Drug therapy with ACE inhibitors
* V̇O2peak \<86% of the medical reference value Voluntary participation
* Written informed consent of the subject to participate in the study


* 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

Exclusion Criteria

* 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 \[Marfan syndrome, Ehlers-Danlos syndrome\])


* 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 \[Marfan syndrome, Ehlers-Danlos syndrome\])
Minimum Eligible Age

20 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Zurich

OTHER

Sponsor Role collaborator

Balgrist University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Walter O Frey, MD

Role: PRINCIPAL_INVESTIGATOR

Balgrist University Hospital, Move>med, Swiss Olympic Center, Zurich, Switzerland

Christian M Schmied, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiology, University Hospital Zurich, Zurich, Switzerland

Locations

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Balgrist University Hospital

Zurich, , Switzerland

Site Status

University Hospital Zurich

Zurich, , Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 26407530 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25262765 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 26937347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23397151 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30916659 (View on PubMed)

Related Links

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Other Identifiers

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KEK-ZH-Nr. 2014-0319

Identifier Type: OTHER

Identifier Source: secondary_id

W 549 ACE-REHAB

Identifier Type: -

Identifier Source: org_study_id

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