TerminatedNCT02845063ACE-REHABUpdated Aug 16, 2023

Effect of ACE Genotype on Cardiovascular Rehabilitation

A Phase 2 interventional study of concentric cardiovascular training and eccentric cardiovascular training in Cardiovascular Disease, sponsored by Balgrist University Hospital. Terminated at 2 sites in Switzerland. Open to participants aged 20 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-16.

Sponsored by Balgrist University Hospital · Phase 2, Interventional, and Treatment

Why this study was terminated

Study terminated

Phase: Phase 2
Study type: Interventional
Enrollment: 60
Allocation: Non-randomized
Ages: 20 Years to 65 Years
Sex: All

Study 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. 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.

Conditions studied

Cardiovascular Disease

Browse trials for

Cardiovascular Diseases 4,904

Keywords

muscle plasticity
exercise
rehabilitation
perfusion
ACE
genotype
hypertension
molecular biology

In context

Cardiovascular Diseases

4,904 studies on the registry are indexed under Cardiovascular Diseases; 919 are open to participants now.

This study's enrollment of 60 is below the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.

Browse Cardiovascular Diseases studies →

Lead sponsor

Balgrist University Hospital is the lead sponsor of 80 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 20 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

Patient group 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

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])

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

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])

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Factorial assignment
Masking: None (open label)
Enrollment: 60 participants (actual)

Study arms

Experimental
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'
Behavioral: concentric cardiovascular training · Genetic: ACE genotyping
Experimental
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'
Behavioral: eccentric cardiovascular training · Genetic: ACE genotyping
Active comparator
concentric cardiovascular training
Healthy subjects will be enrolled in the intervention 'concentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Behavioral: concentric cardiovascular training · Genetic: ACE genotyping
Active comparator
eccentric cardiovascular training
Healthy subjects will be enrolled in the intervention 'eccentric cardiovascular training' and evaluated by the intervention 'ACE genotyping'
Behavioral: eccentric cardiovascular training · Genetic: ACE genotyping

Interventions

Behavioralconcentric 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.
Behavioraleccentric 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.
GeneticACE genotyping
Subjects will be genotyped for the ACE-I/D gene polymorphism.

What researchers measure

Primary outcomes

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.
Time frame: 975 days: May 2016-January 2019
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 \[relative expression per 28S rRNA\]
Time frame: 975 days: May 2016-January 2019
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 \[pixel counts per actin\]
Time frame: 975 days: May 2016-January 2019
Molecular muscle characteristics- phosphorylation
• Phosphorylation of proteins phospho-Y397- FAK, phospho-T421/S424-P70S6K, phospho -T183/Y185-JNK, phospho-S2448-mTOR \[pixel counts per actin\]
Time frame: 975 days: May 2016-January 2019
Molecular muscle characteristics- ACE
• ACE activity \[fmol min-1\]
Time frame: 975 days: May 2016-January 2019
Cellular muscle characteristics - fiber type %
• Distribution of type I, IIA and IIX fibers \[%\]
Time frame: 975 days: May 2016-January 2019
Cellular muscle characteristics - fiber area %
• Area percentage of type I, IIA and IIX fibers \[% area\]
Time frame: 975 days: May 2016-January 2019
Cellular muscle characteristics - fiber type CSA
• Cross sectional area of type I, IIA and IIX fibers \[micrometer2\]
Time frame: 975 days: May 2016-January 2019
Cellular muscle characteristics - Capillary density
• Capillary density \[capillaries micrometer-2\]
Time frame: 975 days: May 2016-January 2019
Cellular muscle characteristics - Capillary-to-fiber ratio
• Capillary-to-fiber ratio
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Maximal Power
• Maximal power during ramp test on ergometer \[Watt\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Critical Power
• Critical power in ramp test on ergometer \[Watt\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Real Power
• Real Power as estimated on the soft robotic device \[Watt\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Reactive Power
• Reactive Power as estimated on the soft robotic device \[Watt\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Negative Power
• Negative Power as estimated on the soft robotic device \[Watt\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Maximal force
• Maximal force during the reactive power test on the soft robotic device \[Newton\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Maximal velocity
• Maximal velocity during the reactive power test on the soft robotic device \[m sec-1\]
Time frame: 975 days: May 2016-January 2019
Functional muscle characteristics - Rate of force development
• Rate of force development as estimated during the Real Power test on the soft robotic device \[meter sec-2\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - muscle oxygenation ramp
• Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during ramp test on ergometer \[%\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - muscle oxygenation robot exercise
• Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during exercise on soft robot \[%\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - hemoglobin ramp
• Total hemoglobin during ramp test on ergometer \[%\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - hemoglobin robot exercise
• Total hemoglobin during exercise on soft robot \[%\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - lipid compounds
• Concentration of lipid compounds in m. vastus lateralis muscle during exercise on soft roboter
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - metabolites
• Concentration of metabolites in m. vastus lateralis muscle during exercise on soft roboter
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - serum glucose
• Concentration of glucose in serum during ramp test on ergometer \[mmol l-1\]
Time frame: 975 days: May 2016-January 2019
Muscle metabolism - serum lactate
• Concentration of lactate in serum during ramp test on ergometer \[mmol l-1\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - Heart rate rest
• Heart rate at rest \[beats per minute\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - Heart rate ramp
• Heart rate in ramp test on ergometer \[beats per minute\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - cardiac output
• Cardiac output \[L min-1\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - ejection fraction
• Ejection fraction
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - Maximal oxygen uptake
• Maximal oxygen uptake (VO2max) during ramp test on ergometer \[ml O2 min-1 kg-1\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - ventilation
• Ventilation during ramp test on ergometer \[L min-1\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - ventilation frequency
• Ventilation frequency ramp test on ergometer \[min-1\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - respiration quotient
• Respiration quotient during ramp test on ergometer \[ L O2 inspired / L CO2 expired\]
Time frame: 975 days: May 2016-January 2019
Cardiovascular function - endurance
Time-to-exhaustion in constant load on ergometer \[seconds\]
Time frame: 975 days: May 2016-January 2019

Study locations

2 sites

Balgrist University Hospital
Zurich, 8008, Switzerland
University Hospital Zurich
Zurich, 8091, Switzerland

References and documents

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 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 16, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02845063
Lead sponsor: Balgrist University Hospital
Collaborators: University of Zurich
Responsible party: Sponsor
First posted: Jul 27, 2016
Start date: May 1, 2016
Primary completion: Jan 1, 2019
Completion: Jan 1, 2020
Last update: Aug 16, 2023

Study contacts

Walter O Frey, MD

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

Christian M Schmied, MD

principal investigator · Cardiology, University Hospital Zurich, Zurich, Switzerland

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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