Effects of a Partially Supervised Conditioning Program in CF (ACTIVATE-CF)

Effects of a Partially Supervised Conditioning Program in CF: an International Multi-centre, Randomized Controlled Trial

Physical activity and exercise have become an accepted and valued component of Cystic Fibrosis care. Regular physical activity and exercise can slow the rate of decline of pulmonary function, improve physical fitness, and enhance quality of life. However, motivating people to be more active is challenging. Supervised exercise programs are expensive and labor intensive, and adherence falls off significantly once supervision ends. Unsupervised or partially supervised programs are less costly and more flexible, but compliance can be more problematic. The primary objective of this study is to evaluate the effects of a 12-months partially supervised exercise intervention along with regular motivation on forced expiratory volume in 1 second (FEV1) in a large international group of cystic fibrosis patients. Secondary endpoints include patient reported quality of life, as well as levels of anxiety and depression, and control of blood sugar. A total of 292 patients with cystic fibrosis 12 years and older with a FEV1 ≥35% predicted will be recruited. Following baseline assessments (2 visits) patients will be randomized into an intervention and a control group. Thereafter, they will be seen every 3 months for assessments in their centre for one year (4 follow-up visits). Along with individual counseling to increase vigorous physical activity by at least 3 hours per week on each clinic visit, the intervention group will document daily exercise and inactivity time and will receive a step counter and they will record their progress with a web-based program. They will also receive monthly phone calls from the study staff. After 6 months, they will continue with the step counter and web-based program for a further 6 months. The control group will receive access to this intervention after 12 months of standardized care. Should this relatively simple program prove successful, this will be made available on a wider scale internationally.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Behavioral: Exercise Intervention

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Mukoviszidose-Ambulanz, Universitätsklinik für Kinder- und Jugendheilkunde,
  • Innsbruck, Austria, 6020
    • Cystische Fibrose Zentrum für Kinder, Jugendliche und Erwachsene
• Canada
  • Quebec
    • Monrtreal, Quebec, Canada, H4A 3J1
      • Montreal Children's Hospital, McGill University Health Centre - Glen Site
• France
  • Hyeres, France, 83406
    • Hôpital Renée Sabran, Service : Maladies respiratoires
  • Lille cedex, France, 59037
    • Hôpital Calmette, Service Pneumologie-immuno-allergologie boulevard du Pr Leclercq
  • Lille cedex, France, 59037
    • Hôpital Jeanne de Flandre, Service: Pneumologie et allergologie pédiatriques
  • Montpellier cedex 5, France, 34295
    • Hôpital Arnaud de Villeneuve, Service: Maladies respiratoires
  • Paris, France, 75015
    • Hôpital Necker, Service : Pneumologie et allergologie pédiatriques
  • Reims, France, 51092
    • Hôpital Maison Blanche, Service : Maladies respiratoires
• Germany
  • Bochum, Germany, 44791
    • Pediatric Pulmonology and CF centre, Children´s Hospital, Ruhr University
  • Dresden, Germany, 01307
    • Klinik und Poliklinik für Kinderheilkunde - Universitäts-Mukoviszidose-Centrum
  • Frankfurt, Germany, 60323
    • Christiane Herzog CF-Zentrum, Goethe Universität
  • Hamburg, Germany, 22763
    • CF Zentrum Hamburg-Altona, Kinderarztpraxis Runge, Sextro,Held
  • Hannover, Germany, 30625
    • CF- Ambulanz, Kinderklinik, Pädiatrische Pneumologie, Allergologie und Neonatologie
  • Mainz, Germany, 55101
    • Zentrum für Kinder- und Jugendmedizin, Pädiatrische Pneumologie, Allergologie und Mukoviszidose
  • Munich, Germany, 81241
    • Praxis für Lungen- und Bronchialheilkunde
  • Münster, Germany, 48149
    • Klinik für Kinder- und Jugendmedizin / Universitätsklinikum
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70174
      • Olgahospital, Klinikum Stuttgart
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Tübingen
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Children´s Hospital of the University
• Netherlands
  • Utrecht, Netherlands
    • University Medical Center, Child Development & Exercise Center, Wilhelmina Children's Hospital
• Switzerland
  • Bern, Switzerland, 3001
    • QuartierBleu, Praxis für Pneumologie am Lindenhofspital
  • Bern, Switzerland
    • Inselspital, Universitätsklinik für Kinderheilkunde, Pneumologie
  • Zurich, Switzerland, 8032
    • Kinderspital, Pneumologie
  • Zurich, Switzerland, 8091
    • UniversitätsSpital, Klinik für Pneumologie
• United Kingdom
  • Scottland
    • Edinburgh, Scottland, United Kingdom, EH9 1LF
      • Royal Hospital for Sick Children
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-1212
      • University of Alabama at Birmingham
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of Cystic Fibrosis
• Age ≥12 years
• Forced expiratory volume in 1 second (FEV1) ≥ 35% predicted
• Access to the internet

Exclusion Criteria:

• Participation in another clinical trial up to 4 weeks prior to the first baseline visit
• Pregnancy/Breastfeeding
• Inability to exercise
• More than 4 hours of reported strenuous physical activities per week currently or up to 3 months prior to baseline measurements and not already planned within the coming 6 months.
• Unstable condition precluding exercise (major hemoptysis or pneumothorax within the last 3 months, acute exacerbation and iv-antibiotics during the last 4 weeks, planned surgery, listed for lung transplantation, major musculoskeletal injuries such as fractures or sprains during the last 2 months, others according to the impression of the doctor)
• Cardiac arrhythmias with exercise
• Requiring additional oxygen with exercise
• Recent diagnosis of diabetes 3 months prior to screening or at screening
• Recent changes in medication 1 month or less prior to screening (systemic steroids, ibuprofen, inhaled antibiotics, mannitol, DNAse, hypertonic saline)
• At least one G551D mutation and not on ivacaftor (VX770) yet but planned start or planned stop of ivacaftor during the trial
• Colonization with Burkholderia cenocepacia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Intervention; Add three hours of intense physical activities per week to baseline activities. Weekly exercise should include at least 30 minutes of strength building activities and at least two hours of aerobic activities. Exercise bouts lasting 20 min or longer will be counted with respect to total weekly training time.	Behavioral: Exercise Intervention; Add three hours of intense physical activities per week to baseline activities. Weekly exercise should include at least 30 minutes of strength building activities and at least two hours of aerobic activities. Exercise bouts lasting 20 min or longer will be counted with respect to total weekly training time.
No Intervention: Control; Keep activity level constant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in forced expiratory volume in 1 second (FEV1; in % predicted using the average of two baseline measurements) from baseline to 6 months in the intervention group compared to controls.	baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak oxygen uptake (%predicted)		baseline to 6 months and baseline to 12 months
Change in maximal aerobic power (%predicted)		baseline to 6 months and baseline to 12 months
Change in measured steps per day		baseline to 6 months and baseline to 12 months
Change in exercise steps per day		baseline to 6 months and baseline to 12 months
Change in reported physical activity		baseline to 6 months and baseline to 12 months
Change in forced expiratory volume in 1 second (FEV1; %predicted)		baseline to 6 months and baseline to 12 months
Change in forced vital capacity (FVC; % predicted)		baseline to 6 months and baseline to 12 months
Change in residual volume in percent of total lung capacity (RV/TLC; %)		baseline to 6 months and baseline to 12 months
Time to first exacerbation		baseline to 6 months and baseline to 12 months
Number of upper respiratory tract infections	from diary	baseline to 6 months and baseline to 12 months
Days on additional oral / intravenous antibiotics	from questionnaire	baseline to 6 months and baseline to 12 months
Change in body mass index (kg/m2)		baseline to 6 months and baseline to 12 months
Change in muscle mass (kg)	estimated from skinfold thickness	baseline to 6 months and baseline to 12 months
Change in percent body fat	estimated from skinfold thickness	baseline to 6 months and baseline to 12 months
Change in Quality of Life scales	from the revised Cystic Fibrosis health-related quality of life Questionnaire (CFQ-R questionnaire)	baseline to 6 months and baseline to 12 months
Change in depression, anxiety and stress scores	from Depression Anxiety Stress Scales	baseline to 6 months and baseline to 12 months
Change in plasma glucose concentrations 1 and 2 hours after a standardized glucose load	standardized oral glucose tolerance test only patients without diabetes mellitus	baseline to 9 months
Adverse events possibly or likely related to exercise	causality as judged by investigator	baseline to 6 months and baseline to 12 months
Severe adverse events		baseline to 6 months and baseline to 12 months
Serious adverse events		baseline to 6 months and baseline to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance with the exercise goal	based on questionnaire and diary	baseline to 6 months and baseline to 12 months
Change in lung clearance index	based on nitrogen multiple breath washout, in selected centres only	baseline to 6 months and baseline to 12 months
Change in time spent in moderate-and-vigorous physical activity	based on accelerometry, in selected centres only	baseline to 6 months and baseline to 12 months
Change in bone mineral density and body composition	based on dual energy x-ray absorptiometry, in selected centres only	baseline to 6 months and baseline to 12 months
Change in mucociliary clearance with exercise	based on nuclear medicine scans, US centres only	baseline to 6 months

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Investigators: Principal Investigator: Helge U Hebestreit, Dr. med., Wuerzburg University Hosptitals

Publications and helpful links

General Publications

• Hebestreit H, Lands LC, Alarie N, Schaeff J, Karila C, Orenstein DM, Urquhart DS, Hulzebos EHJ, Stein L, Schindler C, Kriemler S, Radtke T; ACTIVATE-CF Study Working Group. Effects of a partially supervised conditioning programme in cystic fibrosis: an international multi-centre randomised controlled trial (ACTIVATE-CF): study protocol. BMC Pulm Med. 2018 Feb 8;18(1):31. doi: 10.1186/s12890-018-0596-6.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): October 15, 2018
• Study Completion (Actual): October 15, 2018

Study Registration Dates

• First Submitted: December 5, 2012
• First Submitted That Met QC Criteria: December 5, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Actual): October 22, 2018
• Last Update Submitted That Met QC Criteria: October 18, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Exercise; Motivation; Feedback; pedometer; web-based diary
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: ACT-CF-001

Drug and device information, study documents

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