NCT02845063

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2016

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 27, 2015

Completed
5 months until next milestone

Study Start

First participant enrolled

May 1, 2016

Completed
3 months until next milestone

First Posted

Study publicly available on registry

July 27, 2016

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2020

Completed
Last Updated

August 16, 2023

Status Verified

August 1, 2023

Enrollment Period

2.7 years

First QC Date

November 27, 2015

Last Update Submit

August 14, 2023

Conditions

Cardiovascular Disease

Keywords

muscle plasticityexerciserehabilitationperfusionACEgenotypehypertensionmolecular biology

Outcome Measures

Primary Outcomes (35)

  • 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.

    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 \[relative expression per 28S rRNA\]

    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 \[pixel counts per actin\]

    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 \[pixel counts per actin\]

    975 days: May 2016-January 2019

  • Molecular muscle characteristics- ACE

    • ACE activity \[fmol min-1\]

    975 days: May 2016-January 2019

  • Cellular muscle characteristics - fiber type %

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

    975 days: May 2016-January 2019

  • Cellular muscle characteristics - fiber area %

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

    975 days: May 2016-January 2019

  • Cellular muscle characteristics - fiber type CSA

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

    975 days: May 2016-January 2019

  • Cellular muscle characteristics - Capillary density

    • Capillary density \[capillaries micrometer-2\]

    975 days: May 2016-January 2019

  • Cellular muscle characteristics - Capillary-to-fiber ratio

    • Capillary-to-fiber ratio

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Maximal Power

    • Maximal power during ramp test on ergometer \[Watt\]

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Critical Power

    • Critical power in ramp test on ergometer \[Watt\]

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Real Power

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

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Reactive Power

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

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Negative Power

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

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Maximal force

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

    975 days: May 2016-January 2019

  • Functional muscle characteristics - Maximal velocity

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

    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 \[meter sec-2\]

    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 \[%\]

    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 \[%\]

    975 days: May 2016-January 2019

  • Muscle metabolism - hemoglobin ramp

    • Total hemoglobin during ramp test on ergometer \[%\]

    975 days: May 2016-January 2019

  • Muscle metabolism - hemoglobin robot exercise

    • Total hemoglobin during exercise on soft robot \[%\]

    975 days: May 2016-January 2019

  • Muscle metabolism - lipid compounds

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

    975 days: May 2016-January 2019

  • Muscle metabolism - metabolites

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

    975 days: May 2016-January 2019

  • Muscle metabolism - serum glucose

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

    975 days: May 2016-January 2019

  • Muscle metabolism - serum lactate

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

    975 days: May 2016-January 2019

  • Cardiovascular function - Heart rate rest

    • Heart rate at rest \[beats per minute\]

    975 days: May 2016-January 2019

  • Cardiovascular function - Heart rate ramp

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

    975 days: May 2016-January 2019

  • Cardiovascular function - cardiac output

    • Cardiac output \[L min-1\]

    975 days: May 2016-January 2019

  • Cardiovascular function - ejection fraction

    • Ejection fraction

    975 days: May 2016-January 2019

  • Cardiovascular function - Maximal oxygen uptake

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

    975 days: May 2016-January 2019

  • Cardiovascular function - ventilation

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

    975 days: May 2016-January 2019

  • Cardiovascular function - ventilation frequency

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

    975 days: May 2016-January 2019

  • Cardiovascular function - respiration quotient

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

    975 days: May 2016-January 2019

  • Cardiovascular function - endurance

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

    975 days: May 2016-January 2019

Study Arms (4)

concentric cardiovascular rehabilitation

EXPERIMENTAL

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 trainingGenetic: ACE genotyping

eccentric cardiovascular rehabilitation

EXPERIMENTAL

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 trainingGenetic: ACE genotyping

concentric cardiovascular training

ACTIVE COMPARATOR

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

Behavioral: concentric cardiovascular trainingGenetic: ACE genotyping

eccentric cardiovascular training

ACTIVE COMPARATOR

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

Behavioral: eccentric cardiovascular trainingGenetic: ACE genotyping

Interventions

concentric cardiovascular trainingBEHAVIORAL

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.

concentric cardiovascular rehabilitationconcentric cardiovascular training
eccentric cardiovascular trainingBEHAVIORAL

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.

eccentric cardiovascular rehabilitationeccentric cardiovascular training
ACE genotypingGENETIC

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

concentric cardiovascular rehabilitationconcentric cardiovascular trainingeccentric cardiovascular rehabilitationeccentric cardiovascular training

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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 \[Marfan syndrome, Ehlers-Danlos syndrome\])
  • 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
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Balgrist University Hospital

Zurich, 8008, Switzerland

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

Related Publications (6)

  • 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.

    PMID: 26407530BACKGROUND

  • 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.

    PMID: 25262765BACKGROUND

  • 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.

    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.

    PMID: 26937347BACKGROUND

  • 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.

    PMID: 23397151BACKGROUND

  • 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.

    PMID: 30916659DERIVED

Related Links

MeSH Terms

Conditions

Cardiovascular DiseasesMotor ActivityHypertension

Condition Hierarchy (Ancestors)

BehaviorVascular Diseases

Study Officials

  • Walter O Frey, MD

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

    PRINCIPAL INVESTIGATOR

  • Christian M Schmied, MD

    Cardiology, University Hospital Zurich, Zurich, Switzerland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 27, 2015

First Posted

July 27, 2016

Study Start

May 1, 2016

Primary Completion

January 1, 2019

Study Completion

January 1, 2020

Last Updated

August 16, 2023

Record last verified: 2023-08

Locations

CH(2)