Structured Exercise Training Programme in Idiopathic Pulmonary Fibrosis (Rehab-IPF)

Investigating the Effects of a Structured Responsive Exercise Training Programme in Idiopathic Pulmonary Fibrosis - a Pilot Study

In this single centre non-randomised pilot cohort study we wish to quantify the effect of a twice weekly, 8 week, structured responsive exercise training programme on exercise tolerance, symptoms and health related quality of life in patients with Idiopathic Pulmonary Fibrosis (IPF). We also wish to assess the effect of exercise training on fibrotic processes causing IPF through measurement of blood biomarkers of disease activity.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Idiopathic Pulmonary Fibrosis; Breathlessness
• Intervention / Treatment: Other: Structured Responsive Exercise Training; Other: Usual Care

Detailed Description

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterised by progressive exercise intolerance and breathlessness. In 2012 there were 32 500 people living in the United Kingdom (UK) with IPF. Average life expectancy from time of diagnosis is 2-3 years (Ley et al. 2011). Despite recent advances in drug therapy, therapeutic options are limited and no medication has been found to halt progression of the disease. Pulmonary Rehabilitation (PR) is a structured exercise and education intervention that is well established as a core treatment intervention for patients with Chronic Obstructive Pulmonary Disease (COPD). Current limited evidence shows that PR is safe in patients with IPF and can lead to short-term improvements in exercise tolerance, symptoms and quality of life (Dowman et al. 2014). However the optimal exercise protocol, the longer-term benefits and which group or patients (those with milder or more severe disease) benefit most is unclear. Further it is unknown what mechanisms underlie any improvement and whether exercise training influences the fibrotic process causing IPF.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants aged 18-85 years with a confirmed diagnosis of fibrotic interstitial lung disease (fILD) including; Usual Interstitial Pneumonia, fibrotic Nonspecific interstitial pneumonia (NSIP), Chronic hypersensitivity pneumonitis (chronic HP) and unclassifiable interstitial lung disease (unclassified ILD). Medical Research Council (MRC) breathlessness scale grade 1-3. Clinically stable for 3 months as judged by investigator

Exclusion Criteria:

• Forced Expiratory Volume in 1 second (FEV1) to Forced Vital Capacity (FVC) FEV1/FVC ratio <0.7
• Patients with severe heart failure New York Heart Association (NYHA) grade III or IV or left ventricular systolic function <45%
• Current use of ambulatory or long term oxygen therapy
• Resting oxygen saturations <85% on air
• The presence of infection or exacerbation requiring hospitalization, within 3 months prior to recruitment
• Commencement on anti-fibrotic therapy (Pirfenidone® or Nintedanib®) within 3 months prior to recruitment to the study
• Patients taking oral corticosteroids: unless the dose is less than 15 mg of prednisolone or equivalent, and the dose has been stable for 8 weeks at the time of booking
• Neoplastic disease undergoing treatment or active follow-up
• Current or previous history of sarcoidosis or collagen vascular disease
• Any condition which would prevent completion of cycle-ergometer testing, Pulmonary Function Tests (PFTs) or 6 minute walk test (6-MWT) as judged by the investigator.
• Participation in a Pulmonary Rehabilitation (PR) program in the last 6 months
• Any condition excluding Cardiopulmonary Exercise Testing (CPET) based on the absolute contraindication as the American College of Chest Physicians (ACCP)/ American Thoracic Society (ATS) guidelines 2003 listed here: History of exercise induced syncope, Uncontrolled arrhythmia causing symptoms or hemodynamic compromise, Syncope, Acute endocarditis, Acute myocarditis or pericarditis, Symptomatic severe aortic stenosis, Uncontrolled heart failure, History of acute venous thrombo-embolism, Suspected dissecting aneurysm, uncontrolled asthma, Pulmonary oedema, Mental impairment leading in ability to cooperate, Room air desaturation to <85% unless supplemental O2 is provided for exercise, Acute non-cardiopulmonary disorder that may affect exercise performance/ aggravated by exercise
• Positive Pregnancy test in females of childbearing age.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Structured Responsive Exercise Training; 8 week twice weekly supervised structured responsive static-cycle based exercise training. Training protocol used the same as Loughney et al. 2016	Other: Structured Responsive Exercise Training; Twice weekly, 8 week structured responsive exercise training programme. Protocol used the same as that used in previous EMPOWER Trial (Loughney et al. 2016)
Active Comparator: Standard of Care Arm; Completion of outcome measures only	Other: Usual Care; Continuation of usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in endurance time on fixed load cycle	validated fixed load static cycling test at 75% peak oxygen consumption (VO2 peak) derived from derived from cardiopulmonary exercise testing (CPET) (seconds)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in St. George's Respiratory Questionnaire -IPF (SGRQ-I)	Validated health and quality of life questionnaire for patients with IPF	8 weeks
Change from baseline in Medical Research Council (MRC) Breathlessness Scale	Validated breathlessness questionnaire for respiratory patients	8 weeks
Change from baseline in Revised Borg Breathlessness Score	Validated breathlessness score for respiratory patients	8 weeks
Change from baseline in 6 - Minute Walk Test Distance	Validated exercise capacity assessment for respiratory patients (meters)	8 weeks
Change from baseline Cardiopulmonary Exercise Test variables	A validated tool for access multiple parameters of exercise capacity measures including but not limited to; peak Oxygen consumption ml/kg/minute (VO2 peak), anaerobic threshold ml/kg/minute (AT) , volume of oxygen work rate relationship ml/watt (VO2/Work Rate)	8 weeks
Change from baseline in Fat Mass Index (FMI)	measured by Bioelectrical Impedance Analysis a validated tool to access multiple parameters of body composition.	8 weeks
Change from baseline in Phase Angle measured by	measured by Bioelectrical Impedance Analysis a validated tool to access multiple parameters of body composition.	8 weeks
Change from baseline in Fat Free Mass Index (FFMI)	measured by Bioelectrical Impedance Analysis a validated tool to access multiple parameters of body composition.	8 weeks
Change from baseline in Skeletal Muscle Mass (kg)	measured by Bioelectrical Impedance Analysis a validated tool to access multiple parameters of body composition.	8 weeks
Change from baseline in Body Mass Index (kg/m2)	weight (kg)/height (m)2.	8 weeks
Change from baseline in Council of Nutrition Appetite Questionnaire (CNAQ)	A validated nutritional assessment tool. CNAQ Total Score 8-40 (40 better outcome)	8 weeks
Change from baseline in Simplified nutritional appetite questionnaire (SNAQ) questionnaire	A validated nutritional assessment tool. SNAQ 5-20 (20 better outcome)	8 weeks
Change from baseline in EQ-5D-5L	A validated global health related quality of life PROM. Total Score, Subsections (Mobility, Self-Care, Usual Activity, Pain/Discomfort, Anxiety/Depression. Visual Analogue Scale (0-100)	8 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Blood biomarkers of disease activity in Idiopathic Pulmonary Fibrosis	Plasma/Serum biomarkers including but not limited to Surfactant protein D, Periostin, Matrix Metalloproteinase-7 (MMP-7) and collagen neoepitopes.	8 weeks
Change from baseline in Blood markers of oxidative stress	Plasma markers of oxidative stress including but not limited to 15-F2t-isoprostanes	8 weeks
Change from baseline in serum albumin	Blood markers of systemic inflammation	8 weeks
Change from baseline in serum C-Reactive Protein	Blood markers of systemic inflammation	8 weeks
Change from baseline in serum Interleukin-8	Blood markers of systemic inflammation	8 weeks
Change from baseline in total white blood cell count	Blood markers of systemic inflammation	8 weeks

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Investigators: Principal Investigator: Tim JM Wallis, MA BM MRCP, University Hospital Southampton NHS Foundation Trust

Publications and helpful links

General Publications

• Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev. 2014 Oct 6;(10):CD006322. doi: 10.1002/14651858.CD006322.pub3.
• Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):431-40. doi: 10.1164/rccm.201006-0894CI. Epub 2010 Oct 8.
• Loughney L, West MA, Kemp GJ, Rossiter HB, Burke SM, Cox T, Barben CP, Mythen MG, Calverley P, Palmer DH, Grocott MP, Jack S. The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial. Trials. 2016 Jan 13;17:24. doi: 10.1186/s13063-015-1149-4.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: June 23, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; Exercise training; Idiopathic Pulmonary Fibrosis; Health related quality of life
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Dyspnea
• Other Study ID Numbers: RHM MED1441

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No