Clinical trial NCT02078947: Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure
Official title: Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure- Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Keywords: Diastolic heart failure, Heart failure with preserved ejection fraction, exercise
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: European Commission
name: University of Leipzig
name: University Hospital, Antwerp
name: Medical University of Graz
name: Norwegian University of Science and Technology
name: Charite University, Berlin, Germany
First posted: 2014-03-05
Enrollment: 180
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Aim of the clinical multicenter study (OptimEx-CLIN) is to assess the optimal exercise intervention in patients with Heart Failure with preserved Ejection Fraction (HFpEF; also termed diastolic heart failure) that will best improve peak oxygen uptake (Peak Vo2) and additionally diastolic function (assessed echocardiographically). The investigators hypothesize that exercise training reverses HFpEF and that intensity of exercise training is more important than duration.


Eligibility criteria: Inclusion Criteria:

* Sedentary (structured exercise \< 2x 30 min/wk)
* At least 40 years old
* Preserved systolic function LVEF \> 50%
* Signs and symptoms of heart failure class NYHA II or III
* Diastolic dysfunction (E/é \> 15 or E/é 8-15 and NT-proBNP \> 220 pg/ml)
* Clinically stable for \>= 6 weeks
* Optimal medical treatment for \>= 6 weeks
* Written informed consent

Exclusion Criteria:

* Non- HFpEF causes for HF symptoms (significant valvular or coronary disease, uncontrolled hypertension or arrhythmias, primary cardiomyopathies)
* Significant pulmonary disease (FEV1 \< 50% predicted, COPD GOLD III-IV)
* Inability to exercise or conditions that may interfere with exercise intervention
* Myocardial infarction in the previous three months
* Signs of ischemia during exercise testing
* Comorbidity that may influence one- year prognosis
* Participation in another clinical trial

Primary outcomes:
measure: Change in Peak VO2 after three months
timeFrame: Baseline and three months
Secondary outcomes:
measure: Change in E/e' (representing diastolic filling pressure) at baseline and three months
timeFrame: three months
measure: Change in E/e' at baseline and 12 months
timeFrame: 12 months
measure: Change in Peak VO2 at baseline and 12 months
timeFrame: 12 months
measure: Change in NTproBNP at baseline and three months
timeFrame: three months
measure: Change in NTproBNP at baseline and 12 months
timeFrame: 12 months
measure: Change in health related quality of life at baseline and three months
timeFrame: three months
measure: Change in health related Quality of life at baseline and 12 months
timeFrame: 12 months
measure: Change in Left Atrial Volume Index (LAVI) at baseline and three months
timeFrame: three months
measure: Change in Left Atrial Volume Index (LAVI) at baseline and 12 months
timeFrame: 12 months
measure: Change in e' medial at baseline and three months
timeFrame: three months
measure: Change in e' at baseline and 12 months
timeFrame: 12 months
measure: Change in submaximal exercise capacity at baseline and three months
timeFrame: three months
measure: Change in submaximal exercise capacity at baseline and 12 months
timeFrame: 12 months
measure: Change in VE/VCO2 slope at baseline and three months
timeFrame: three months
measure: Change in VE/VCO2 slope at baseline and 12 months
timeFrame: 12 months
measure: Change in Flow Mediated Dilation (FMD) at baseline and three months
timeFrame: three months
measure: Change in Flow Mediated Dilation (FMD) at baseline and 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Department of Cardiology, Antwerp University Hospital
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Leipzig
country: Germany
facility: Klinik für Innere Medizin/ Kardiologie, Herzzentrum Leipzig- Universitätsklinik
city: Munich
country: Germany
facility: Department of Prevention, Rehabilitation and Sports Medicine, Technische Universität München
Study officials:
affiliation: Technische Universität München, Munich, Germany
name: Martin Halle, M.D.
role: STUDY_DIRECTOR
affiliation: Technische Universität München, Munich, Germany
name: Martin Halle, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Burkert Pieske, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Antwerp University Hospital, Belgium
name: Christiaan Vrints, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Center Leipzig, Leipzig, Germany
name: Volker Adams, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Norwegian University of Science and Technology, Trondheim, Norway
name: Ulrik Wisløff, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart Center Leipzig, Leipzig, Germany
name: Axel Linke, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Frank Edelmann, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gevaert AB, Witvrouwen I, Van Craenenbroeck AH, Van Laere SJ, Boen JRA, Van de Heyning CM, Belyavskiy E, Mueller S, Winzer E, Duvinage A, Edelmann F, Beckers PJ, Heidbuchel H, Wisloff U, Pieske B, Adams V, Halle M, Van Craenenbroeck EM; OptimEx-Clin Study Group. miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial. Eur J Prev Cardiol. 2021 Dec 29;28(15):1722-1733. doi: 10.1093/eurjpc/zwab151.
citation: Mueller S, Haller B, Halle M; OptimEx-Clin Study Group. Effect of Training on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction-Reply. JAMA. 2021 Aug 24;326(8):772-773. doi: 10.1001/jama.2021.10061. No abstract available.
citation: Winzer EB, Augstein A, Schauer A, Mueller S, Fischer-Schaepmann T, Goto K, Hommel J, van Craenenbroeck EM, Wisloff U, Pieske B, Halle M, Linke A, Adams V. Impact of Different Training Modalities on Molecular Alterations in Skeletal Muscle of Patients With Heart Failure With Preserved Ejection Fraction: A Substudy of the OptimEx Trial. Circ Heart Fail. 2022 Oct;15(10):e009124. doi: 10.1161/CIRCHEARTFAILURE.121.009124. Epub 2022 Oct 6.
citation: Gevaert AB, Mueller S, Winzer EB, Duvinage A, Van de Heyning CM, Pieske-Kraigher E, Beckers PJ, Edelmann F, Wisloff U, Pieske B, Adams V, Halle M, Van Craenenbroeck EM; OptimEx-Clin Study Group. Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study. Front Physiol. 2022 Feb 10;12:757268. doi: 10.3389/fphys.2021.757268. eCollection 2021.
citation: Mueller S, Winzer EB, Duvinage A, Gevaert AB, Edelmann F, Haller B, Pieske-Kraigher E, Beckers P, Bobenko A, Hommel J, Van de Heyning CM, Esefeld K, von Korn P, Christle JW, Haykowsky MJ, Linke A, Wisloff U, Adams V, Pieske B, van Craenenbroeck EM, Halle M; OptimEx-Clin Study Group. Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2021 Feb 9;325(6):542-551. doi: 10.1001/jama.2020.26812.
citation: Suchy C, Massen L, Rognmo O, Van Craenenbroeck EM, Beckers P, Kraigher-Krainer E, Linke A, Adams V, Wisloff U, Pieske B, Halle M. Optimising exercise training in prevention and treatment of diastolic heart failure (OptimEx-CLIN): rationale and design of a prospective, randomised, controlled trial. Eur J Prev Cardiol. 2014 Nov;21(2 Suppl):18-25. doi: 10.1177/2047487314552764.