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The Effect of Adding Exercise Training to Optimal Therapy in PAH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02961023
Recruitment Status : Completed
First Posted : November 10, 2016
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Martin Johnson, National Health Service, United Kingdom

Brief Summary:

Exercise capacity (EC) is limited in pulmonary arterial hypertension (PAH) by impaired right ventricular (RV) function and inability to increase stroke volume (SV). Disease targeted therapy, increases EC by improving SV. Additional factors may contribute to exercise limitation:

  • Peripheral and respiratory muscle dysfunction
  • Autonomic dysfunction
  • An altered profile of inflammation
  • Mitochondrial dysfunction.

The enhancement of EC achieved pharmacologically may therefore be limited. Exercise training in PAH improves EC and quality of life (QOL). The changes in physiology responsible for this improvement are not clear. Patients with PAH stable on optimal oral therapy, but not meeting treatment goals, will be enrolled in a 30-week randomised exercise training program.

One arm will undertake training for 15 weeks (3 weeks residential, 12 outpatient), the other will receive standard care for 15 weeks then 15 weeks training.

Aims:

  1. Demonstrate that exercise training can enhance EC and QOL when added to optimal drug therapy a UK PAH population.
  2. Explore mechanisms of exercise limitation and factors that improve with training, assessing:

    • Cardiac function
    • Skeletal muscle function
    • Autonomic function
    • Respiratory muscle strength
    • Serum and muscle profile of inflammation

Primary outcomes (15 weeks)

  1. 6 minute walk distance
  2. QOL
  3. RV ejection fraction

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Other: Exercise therapy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Adding Exercise Training to Optimal Therapy in Pulmonary Arterial Hypertension
Study Start Date : February 2016
Actual Primary Completion Date : July 2018
Actual Study Completion Date : July 2018


Arm Intervention/treatment
Active Comparator: Training
15 patients are randomised to receive 15 weeks exercise therapy as per study protocol at point of study entry.
Other: Exercise therapy

3-week residential phase and 12-week outpatient phase.

Residential phase

  • Exercise will be supervised by a physiotherapist and prescribed based on cardiopulmonary exercise testing.
  • A monitored daily program of exercise involving bicycle ergometry, walking, breathing exercises, dumbbell exercises 5 days per week.
  • 1.5 to 2 hours of exercise will be performed daily, with rest intervals.
  • At weekends, lower intensity, unsupervised exercise mirroring the outpatient phase
  • Ongoing exercise prescription will be based on tolerability, progress and HR

Outpatient phase

  • A training manual will be compiled based on the subjects exercise performance during the residential program and tailored specifically to their needs
  • Participants will be provided with a cycle ergometer, weights and a HR monitor
  • Weekly telephone contact will be made by the study doctor or physiotherapist, with adjustments made to training prescription as necessary

Control
15 patients are randomised to receive 15 weeks of standard care, acting as a control arm, followed by 15 weeks of exercise therapy.
Other: Exercise therapy

3-week residential phase and 12-week outpatient phase.

Residential phase

  • Exercise will be supervised by a physiotherapist and prescribed based on cardiopulmonary exercise testing.
  • A monitored daily program of exercise involving bicycle ergometry, walking, breathing exercises, dumbbell exercises 5 days per week.
  • 1.5 to 2 hours of exercise will be performed daily, with rest intervals.
  • At weekends, lower intensity, unsupervised exercise mirroring the outpatient phase
  • Ongoing exercise prescription will be based on tolerability, progress and HR

Outpatient phase

  • A training manual will be compiled based on the subjects exercise performance during the residential program and tailored specifically to their needs
  • Participants will be provided with a cycle ergometer, weights and a HR monitor
  • Weekly telephone contact will be made by the study doctor or physiotherapist, with adjustments made to training prescription as necessary




Primary Outcome Measures :
  1. 6 minute walk distance [ Time Frame: 15 weeks ]
    Change in distance walked in 6 minutes from baseline following 15 weeks of exercise therapy

  2. Quality of life [ Time Frame: 15 weeks ]
    Change in pulmonary hypertension specific (EMPHASIS and CAMPHOR) and generic (SF-36 v2) quality of life scores from baseline to 15 weeks following exercise therapy.

  3. Right Ventricular Ejection Fraction [ Time Frame: 15 weeks ]
    Change in right ventricular ejection fraction from baseline to 15 weeks as measured by cardiac magnetic resonance imaging.


Secondary Outcome Measures :
  1. Peak oxygen uptake [ Time Frame: 15 weeks ]
    Peak oxygen uptake as measured by standard incremental cardiopulmonary exercise testing (CPET) at 15 weeks in addition to all other standard CPET variables

  2. Muscle strength and endurance [ Time Frame: 15 weeks ]
    change in quadriceps strength and endurance, and hand grip endurance and strength from baseline to 15 weeks, as measured by a myometer

  3. Transfer factor for lung carbon monoxide [ Time Frame: 3 weeks ]
    Transfer factor for lung carbon monoxide as measured during standard pulmonary function testing. Change from baseline to 3 weeks.

  4. Respiratory muscle strength [ Time Frame: 3 weeks ]
    change maximum inspiratory and maximum expiratory pressure measured following 3 weeks of exercise therapy.

  5. Pulmonary vascular resistance [ Time Frame: 15 weeks ]
    Change from baseline to 15 weeks, of pulmonary vascular resistance and total pulmonary resistance as measured during resting and exercise right heart catheterisation

  6. Cardiac Output at rest and peak exercise [ Time Frame: 15 weeks ]
    Change in cardiac output from baseline to 15 weeks as measured by right heart catheterisation at rest and on supine exercise

  7. Change in resting and peak exercise mixed venous oxygen saturation [ Time Frame: 15 weeks ]
    Change in mixed venous oxygen saturation from baseline to week 15, as measured from the central pulmonary artery during resting and exercise right heart catheterisation.

  8. Left ventricular ejection fraction [ Time Frame: 15 weeks ]
    Left ventricular ejection fraction as measured by cardiac MRI - change from baseline to 15 weeks following exercise therapy


Other Outcome Measures:
  1. Profile of inflammatory cytokines [ Time Frame: 15 weeks ]
    change in profile of pro-inflammatory serum cytokines as measured by multiplex ELISA from baseline to 15 weeks following exercise training.

  2. Insulin resistance [ Time Frame: 15 weeks ]
    Change in HOMA-IR score from baseline to 15 weeks following exercise therapy (scored from fasting serum c-peptide and glucose)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • World health organisation functional class (WHO-FC) II-III
  • Stable on optimal disease targeted therapy for ≥ 3 months
  • 18 years of age or older

Exclusion criteria

  • Unable to provide informed consent
  • Significant peripheral vascular disease, neurological or musculoskeletal comorbidity
  • Exercise induced syncope, cardiac arrhythmia or chest pain
  • Pregnancy
  • Specific component exclusions: Cardiac MRI (CMR): Any contraindication to MRI

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02961023


Locations
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United Kingdom
Dr Martin Johnson
Glasgow City, United Kingdom, G81 4DY
Sponsors and Collaborators
National Health Service, United Kingdom

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Responsible Party: Martin Johnson, Dr Martin K Johnson, National Health Service, United Kingdom
ClinicalTrials.gov Identifier: NCT02961023    
Other Study ID Numbers: 15/CARD/21, REC 15-WS-197
First Posted: November 10, 2016    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases