Effect of Exercise and Respiratory Therapy on Right Ventricular Function in Severe Pulmonary Hypertension

NCT ID: NCT04224012

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2024-08-31

Brief Summary

Chronic pulmonary hypertension (PH) is associated with impaired exercise capacity, quality of life and right ventricular function.The disease is characterized by an increase of pulmonary vascular resistance and pulmonary arterial pressure, leading to right heart insufficiency. In later stages of the disease, the right heart is not able to further increase right ventricular contractility (cardiac index) during exercise. Within the last decade, new disease-targeted medical therapies have been approved for treatment of pulmonary arterial hypertension (PAH). Sequential and upfront combinations of these agents have shown to further improve symptoms, 6-minute walking distance (6-MWD) and hemodynamics in PAH patients.

Previous training studies have suggested that exercise training as add-on to medical treatment is highly effective improving exercise capacity, quality of life and symptoms. Prospective studies with a 24±12 months follow-up period suggested that exercise training may also improve the rate of clinical worsening events as the need for hospitalization, additional PH-medication, lung-transplantation and death.

There is also first data that exercise training may have a positive impact on the right ventricular function.

This randomised controlled study aims to assess whether exercise training

Detailed Description

The aim of this prospective, randomized, controlled study in patients with pulmonary hypertension, who are under stable optimized treatment for at least 2 months, is to examine the effect of an additional exercise and respiratory therapy on the right heart function.

The primary endpoint of this study is the right heart function, measured by cardiac index during exercise invasively determined by right heart catheterization. More hemodynamic parameters for the determination of the right heart function as well as clinical and molecular parameters are relevant to record the physiological effect of the training. The molecular parameters are composed of laboratory parameter and inflammatory parameter as well as genetic analyses, measurements of epigenetic changes measured by microRNA Expressions and DNA-methylation and imunohistochemical measurements of the quadriceps musculature.

The study parameters will be assessed in the patient's routine examinations. Clinical parameters comprise of hemodynamic assessment of pulmonary arterial pressure during exercise, pump function of left and right ventricle, and further echocardiographic parameters. Improvement of exercise capacity will be measured by the change of six-minute walking distance, the breathing economics, the world health organization functional class (WHO functional class), peak oxygen consumption and blood gas analysis. The quality of life will be assessedwith the SF-36 questionnaire.Data for survival analysis will be gained by structured phone interviews . The safety of the training is warranted by long-term, rest- and stress-ECG, safety laboratory, systemic blood pressure, heart frequency, oxygen saturation and occurrence of adverse events. In addition to the routine examinations at baseline and after 15 weeks, a right heart catheterization will be performed.

Patients will be examined in the Thoraxklinik Heidelberg. Patients of the training group will take part in a specific, 3-week inpatient training program at the rehabilitation center Königstuhl Heidelberg right after the baseline examination. The training program consists of exercise and respiratory therapy as well as a mental gait training. Respiratory therapy will be performed 5 times/week for 30 minutes. Furthermore, 15-25 minutes low dosed interval training on a bicycle ergometer, dumbbell training of particular muscle groups with low weights and supervised walks on ground-level will be scheduled 5-7 times/week. Three- to five times a week a "mental gait training" is conducted to estimate the patient's individual physical abilities and limitations. The heart rate during exerciseand the intensity of the training will be closely monitored and individually adjusted. After three weeks of in-hospital rehabilitation the patients are asked to continue the training for twelve further weeks at home. All patients will be examined before the training program, at the end of the in-hospital phase after three weeks and after 15 weeks. Patients of the control group will continue with their lifestyle without individual training prescriptions. After having participated in the study, patients of the control group will also be offered to take part in the training program.

The control examinations cover the medical history, WHO functional class, physical examination, ECG, echocardiography at rest and during exercise, spiroergometry, quality of life, blood-gas analysis, lung function, 6-minute walking distance, oxygen saturation, blood pressure and heart rate, laboratory tests. An optional magnet resonance imaging at the beginning and after three months may also be conducted. At baseline, an optional genetic assessment will be performed; and at the beginning, after three and 15 weeks the expression levels of micro RNA and methylation of the DNA will be assessed. A biopsy of the quadriceps musculature will optionally be carried out at baseline and after 15 weeks. Medication will remain stable throughout the study.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Conventional therapy group (control group)

patients of the control Group receive usual care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventional group (training group)

Specialized exercise and respiratory therapy for patients with pulmonary hypertension

Group Type: EXPERIMENTAL

Exercise and respiratory therapy

Intervention Type: OTHER

Three weeks in-Hospital Rehabilitation program with continuation of exercise Training at home

Interventions

Exercise and respiratory therapy

Three weeks in-Hospital Rehabilitation program with continuation of exercise Training at home

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Consent form
• Men and women >18 years
• Symptomatic PH (WHO-FC II-IV) invasive diagnostis with right heart catheterization: mPAP >25mmHg and a stable optimized treatment for at least 2 month
• Ptients who are able to understand and agree to participate in the study

Exclusion Criteria

• Pregnancy or breast feeding
• Variation in the medication during the last 2 months
• Patients with signs of right heart decompensation
• Major walking problems
• Unclear diagnosis
• No invasive clarification of the PH
• Acute illness, infections and fever
• Grave lung disease with FEV1 <50% or TLC <70% from target
• Further conclusion criteria are followed: acrive myokarditis, unstable angina pectoris, movement induced venr´tricular rhythmdisturbance, decompensation of the right hart insufficiency, meaningful heartvitien, hyperthrophic obstructive cardiomyopathie or a high grade reduced left ventricular pumpu function

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Ekkehard Gruenig

Prof. Dr. med. Ekkehard Grünig; Head of centre for pulmonary hypertension

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Centre for Pulmonary Hypertension at the Thoraxklinik, Heidelberg University Hospital

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Facility Contacts

Ekkehard Grünig, MD

Role: primary

ekkehard.gruenig@med.uni-heidelberg.de

+496221396 ext. 8053

Other Identifiers

TRAIN-01

Identifier Type: -

Identifier Source: org_study_id