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Trial record 3 of 6 for:    LIPE

Effect of ACE Genotype on Cardiovascular Rehabilitation (ACE-REHAB)

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ClinicalTrials.gov Identifier: NCT02845063
Recruitment Status : Recruiting
First Posted : July 27, 2016
Last Update Posted : August 9, 2016
Sponsor:
Collaborator:
University of Zurich
Information provided by (Responsible Party):
Balgrist University Hospital

Tracking Information
First Submitted Date  ICMJE November 27, 2015
First Posted Date  ICMJE July 27, 2016
Last Update Posted Date August 9, 2016
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2016)
  • ACE I/D genotype [ Time Frame: 975 days: May 2016-January 2019 ]
    Genotype of the assessed insertion/deletion gene polymorphism of angiotensin converting enzyme ACE, i.e. ACE-II, ACE-ID or ACE-DD.
  • Molecular muscle characteristics - mRNA [ Time Frame: 975 days: May 2016-January 2019 ]
    • 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]
  • Molecular muscle characteristics- protein [ Time Frame: 975 days: May 2016-January 2019 ]
    • 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]
  • Molecular muscle characteristics- phosphorylation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Phosphorylation of proteins phospho-Y397- FAK, phospho-T421/S424-P70S6K, phospho -T183/Y185-JNK, phospho-S2448-mTOR [pixel counts per actin]
  • Molecular muscle characteristics- ACE [ Time Frame: 975 days: May 2016-January 2019 ]
    • ACE activity [fmol min-1]
  • Cellular muscle characteristics - fiber type % [ Time Frame: 975 days: May 2016-January 2019 ]
    • Distribution of type I, IIA and IIX fibers [%]
  • Cellular muscle characteristics - fiber area % [ Time Frame: 975 days: May 2016-January 2019 ]
    • Area percentage of type I, IIA and IIX fibers [% area]
  • Cellular muscle characteristics - fiber type CSA [ Time Frame: 975 days: May 2016-January 2019 ]
    • Cross sectional area of type I, IIA and IIX fibers [micrometer2]
  • Cellular muscle characteristics - Capillary density [ Time Frame: 975 days: May 2016-January 2019 ]
    • Capillary density [capillaries micrometer-2]
  • Cellular muscle characteristics - Capillary-to-fiber ratio [ Time Frame: 975 days: May 2016-January 2019 ]
    • Capillary-to-fiber ratio
  • Functional muscle characteristics - Maximal Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal power during ramp test on ergometer [Watt]
  • Functional muscle characteristics - Critical Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Critical power in ramp test on ergometer [Watt]
  • Functional muscle characteristics - Real Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Real Power as estimated on the soft robotic device [Watt]
  • Functional muscle characteristics - Reactive Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Reactive Power as estimated on the soft robotic device [Watt]
  • Functional muscle characteristics - Negative Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Negative Power as estimated on the soft robotic device [Watt]
  • Functional muscle characteristics - Maximal force [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal force during the reactive power test on the soft robotic device [Newton]
  • Functional muscle characteristics - Maximal velocity [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal velocity during the reactive power test on the soft robotic device [m sec-1]
  • Functional muscle characteristics - Rate of force development [ Time Frame: 975 days: May 2016-January 2019 ]
    • Rate of force development as estimated during the Real Power test on the soft robotic device [meter sec-2]
  • Muscle metabolism - muscle oxygenation ramp [ Time Frame: 975 days: May 2016-January 2019 ]
    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during ramp test on ergometer [%]
  • Muscle metabolism - muscle oxygenation robot exercise [ Time Frame: 975 days: May 2016-January 2019 ]
    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during exercise on soft robot [%]
  • Muscle metabolism - hemoglobin ramp [ Time Frame: 975 days: May 2016-January 2019 ]
    • Total hemoglobin during ramp test on ergometer [%]
  • Muscle metabolism - hemoglobin robot exercise [ Time Frame: 975 days: May 2016-January 2019 ]
    • Total hemoglobin during exercise on soft robot [%]
  • Muscle metabolism - lipid compounds [ Time Frame: 975 days: May 2016-January 2019 ]
    • Concentration of lipid compounds in m. vastus lateralis muscle during exercise on soft roboter
  • Muscle metabolism - metabolites [ Time Frame: 975 days: May 2016-January 2019 ]
    • Concentration of metabolites in m. vastus lateralis muscle during exercise on soft roboter
  • Muscle metabolism - serum glucose [ Time Frame: 975 days: May 2016-January 2019 ]
    • Concentration of glucose in serum during ramp test on ergometer [mmol l-1]
  • Muscle metabolism - serum lactate [ Time Frame: 975 days: May 2016-January 2019 ]
    • Concentration of lactate in serum during ramp test on ergometer [mmol l-1]
  • Cardiovascular function - Heart rate rest [ Time Frame: 975 days: May 2016-January 2019 ]
    • Heart rate at rest [beats per minute]
  • Cardiovascular function - Heart rate ramp [ Time Frame: 975 days: May 2016-January 2019 ]
    • Heart rate in ramp test on ergometer [beats per minute]
  • Cardiovascular function - cardiac output [ Time Frame: 975 days: May 2016-January 2019 ]
    • Cardiac output [L min-1]
  • Cardiovascular function - ejection fraction [ Time Frame: 975 days: May 2016-January 2019 ]
    • Ejection fraction
  • Cardiovascular function - Maximal oxygen uptake [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal oxygen uptake (VO2max) during ramp test on ergometer [ml O2 min-1 kg-1]
  • Cardiovascular function - ventilation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Ventilation during ramp test on ergometer [L min-1]
  • Cardiovascular function - ventilation frequency [ Time Frame: 975 days: May 2016-January 2019 ]
    • Ventilation frequency ramp test on ergometer [min-1]
  • Cardiovascular function - respiration quotient [ Time Frame: 975 days: May 2016-January 2019 ]
    • Respiration quotient during ramp test on ergometer [ L O2 inspired / L CO2 expired]
  • Cardiovascular function - endurance [ Time Frame: 975 days: May 2016-January 2019 ]
    Time-to-exhaustion in constant load on ergometer [seconds]
Original Primary Outcome Measures  ICMJE
 (submitted: July 22, 2016)
  • ACE I/D genotype [ Time Frame: 975 days: May 2016-January 2019 ]
    Genotype of the assessed insertion/deletion gene polymorphism of angiotensin converting enzyme ACE, i.e. ACE-II, ACE-ID or ACE-DD.
  • Molecular muscle characteristics - mRNA [ Time Frame: 975 days: May 2016-January 2019 ]
    • 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]
  • Molecular muscle characteristics- protein [ Time Frame: 975 days: May 2016-January 2019 ]
    • 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]
  • Molecular muscle characteristics- phosphorylation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Phosphorylation of proteins phospho-Y397- FAK, phospho-T421/S424-P70S6K, phospho -T183/Y185-JNK, phospho-S2448-mTOR [pixel counts per actin]
  • Molecular muscle characteristics- ACE [ Time Frame: 975 days: May 2016-January 2019 ]
    • ACE activity [fmol min-1]
  • Cellular muscle characteristics - fiber type % [ Time Frame: 975 days: May 2016-January 2019 ]
    • Distribution of type I, IIA and IIX fibers [%]
    • Area percentage of type I, IIA and IIX fibers [% area]
  • Cellular muscle characteristics - fiber type CSA [ Time Frame: 975 days: May 2016-January 2019 ]
    • Cross sectional area of type I, IIA and IIX fibers [micrometer2]
  • Cellular muscle characteristics - capillarisation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Capillary density [capillaries micrometer-2]
    • Capillary-to-fiber ratio
  • Functional muscle characteristics - Power [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal power during ramp test on ergometer [Watt]
    • Critical power in ramp test on ergometer [Watt]
    • Real Power as estimated on the soft robotic device [Watt]
    • Reactive Power as estimated on the soft robotic device [Watt]
    • Negative Power as estimated on the soft robotic device [Watt]
  • Functional muscle characteristics - Force [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal force during the reactive power test on the soft robotic device [Newton]
  • Functional muscle characteristics - Impulse [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal velocity during the reactive power test on the soft robotic device [m sec-1]
    • Rate of force development as estimated during the Real Power test on the soft robotic device [meter sec-2]
  • Muscle metabolism - oxygenation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during ramp test on ergometer [%]
    • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during exercise on soft roboter [%]
    • Total hemoglobin during ramp test on ergometer [%]
    • Total hemoglobin during exercise on soft roboter [%]
  • Muscle metabolism - metabolites [ Time Frame: 975 days: May 2016-January 2019 ]
    • Concentration of lipid compounds in m. vastus lateralis muscle during exercise on soft roboter
    • Concentration of metabolites in m. vastus lateralis muscle during exercise on soft roboter
    • Concentration of glucose in serum during ramp test on ergometer [mmol l-1]
    • Concentration of lactate in serum during ramp test on ergometer [mmol l-1]
  • Cardiovascular function - heart rate [ Time Frame: 975 days: May 2016-January 2019 ]
    • Heart rate at rest [beats per minute]
    • Heart rate in ramp test on ergometer [beats per minute]
  • Cardiovascular function - cardiac output [ Time Frame: 975 days: May 2016-January 2019 ]
    • Cardiac output [L min-1]
    • Ejection fraction
  • Cardiovascular function - ventilation [ Time Frame: 975 days: May 2016-January 2019 ]
    • Maximal oxygen uptake (VO2max) during ramp test on ergometer [ml O2 min-1 kg-1]
    • Ventilation during ramp test on ergometer [L min-1]
    • Ventilation frequency ramp test on ergometer [min-1]
    • Respiration quotient during ramp test on ergometer [ L O2 inspired / L CO2 expired]
  • Cardiovascular function - endurance [ Time Frame: 975 days: May 2016-January 2019 ]
    Time-to-exhaustion in constant load on ergometer [seconds]
Change History Complete list of historical versions of study NCT02845063 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of ACE Genotype on Cardiovascular Rehabilitation
Official Title  ICMJE Effects of ACE Genotype on Muscular and Functional Adaptations Following a Cardiovascular Rehabilitation Program
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cardiovascular Disease
Intervention  ICMJE
  • Behavioral: 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.
  • 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.
  • Genetic: ACE genotyping
    Subjects will be genotyped for the ACE-I/D gene polymorphism.
Study Arms  ICMJE
  • 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'
    Interventions:
    • 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'
    Interventions:
    • 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'
    Interventions:
    • 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'
    Interventions:
    • Behavioral: eccentric cardiovascular training
    • Genetic: ACE genotyping
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 22, 2016)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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])
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Martin Flück, PhD +41 44 386 3791 mflueck@research.balgrist.ch
Contact: Marco Toigo, PhD +41 44 386 3791 mtoigo@research.balgrist.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02845063
Other Study ID Numbers  ICMJE W 549 ACE-REHAB
KEK-ZH-Nr. 2014-0319 ( Other Identifier: Ethics Committee of the Canton Zurich, Switzerland )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Balgrist University Hospital
Study Sponsor  ICMJE Balgrist University Hospital
Collaborators  ICMJE University of Zurich
Investigators  ICMJE
Principal Investigator: 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
PRS Account Balgrist University Hospital
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP