The Effect of Adding Exercise Training to Optimal Therapy in PAH

NCT02961023 | Completed DMC

• 1 other identifier: 15/CARD/21, REC 15-WS-197
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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:
• Demonstrate that exercise training can enhance EC and QOL when added to optimal drug therapy a UK PAH population.
• 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)
• 6 minute walk distance
• QOL
• RV ejection fraction

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (3)

• 6 minute walk distance

  Change in distance walked in 6 minutes from baseline following 15 weeks of exercise therapy

  15 weeks

• Quality of life

  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.

  15 weeks

• Right Ventricular Ejection Fraction

  Change in right ventricular ejection fraction from baseline to 15 weeks as measured by cardiac magnetic resonance imaging.

  15 weeks

Secondary Outcomes (8)

• Peak oxygen uptake

  15 weeks

• Muscle strength and endurance

  15 weeks

• Transfer factor for lung carbon monoxide

  3 weeks

• Respiratory muscle strength

  3 weeks

• Pulmonary vascular resistance

  15 weeks

Other Outcomes (2)

• Profile of inflammatory cytokines

  15 weeks

• Insulin resistance

  15 weeks

Study Arms (2)

Training

ACTIVE COMPARATOR

15 patients are randomised to receive 15 weeks exercise therapy as per study protocol at point of study entry.

Other: Exercise therapy

Control

OTHER

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

Interventions

Exercise therapy OTHER

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; Training

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Unable to provide informed consent
• Significant peripheral vascular disease, neurological or musculoskeletal comorbidity
• Exercise induced syncope, cardiac arrhythmia or chest pain
• Pregnancy

Sponsors & Collaborators

• National Health Service, United Kingdom: lead

Study Sites (1)

Dr Martin Johnson

Glasgow, G81 4DY, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Exercise Therapy

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Martin K Johnson

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: November 10, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 20, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)