Feasibility of Home-based Exercise Program for Adults With Cystic Fibrosis to Improve Patient-centered Outcomes, Including a Novel Measure of Ventilation
Phase: PHASE2
Conditions: Cystic Fibrosis
Sponsor: University of Kansas Medical Center

 
 
 
 
 
Feasibility of Home-based Exercise Program for Adults With Cystic Fibrosis 
 
Identiﬁers: NCT05239611   Unique Protocol ID: STUDY00146919 
 
 
 
Date August 5th 2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
This was a randomized controlled pilot and feasibility study or a home-based exercise 
program among PwCF. Participants were recruited from The University of Kansas Health 
System (TUKHS) CF outpatient clinic. All study procedures were approved by the University 
of Kansas Medical Center Institutional Review Board and written informed consent was 
obtained from all participants (IRB number CR00020120). 
 
Participants 
 
Adults with CF (two conﬁrmatory CF mutations or sweat chloride > 60 mmol/L) who were 
18 years of age or older and stable on HEMT elexacaftor/tezacaftor/ivacaftor (ETI) for ≥ 3 
months with clearance from their CF physician were eligible to participate. Exclusion 
criteria included completion of ≥ 150 minutes of structured exercise per week for the last X 
time, pregnancy, post solid organ transplant, active treatment for mycobacterial infections, 
oxygen dependent at rest or with exercise, FEV1 < 40% of predicted, clinical evidence of cor 
pulmonale, untreated arterial hypertension (resting systolic blood pressure >140 mm Hg, 
diastolic blood pressure > 90 mmHg), systolic blood pressure less than 90 mm Hg while 
standing, congestive heart issues, active treatment for Allergic Bronchopulmonary 
Aspergillosis (ABPA), pulmonary exacerbation within 4 weeks prior to Day 1, or changes in 
therapy (including antibiotics) for pulmonary disease within 4 weeks prior to Day 1, 
signiﬁcant hemoptysis within 4 weeks prior to Day 1 (≥5 mL of blood in one coughing 
episodes or >30 mL of blood in a 24 hours period), and ongoing participation in an 
investigational drug study within 60 days prior to Day 1. 
 
Eligible participants who consented were randomized 1:1 via a computer-generated 
randomization technique to either the intervention or control group. Participant 
demographics, incremental meter shuttle walk test (IMSWT), spirometry, xenon magnetic 
resonance imaging (Xe-MRI), the Cystic Fibrosis Questionnaire Revised (CFQ-R), and 
surveys regarding physical activity were completed at baseline and upon study completion. 
Semi-structured interviews evaluating exercise were completed in the intervention group at 
the conclusion of the follow-up visit. 
 
Intervention/Exercise Protocol 
 
Those randomized to the intervention group were assigned to an exercise coach and asked 
to wear a wrist-worn Garmin vivosmart 4 actigraph during physical activity. Participants 
were asked to complete 12 weeks of progressive home-based exercise program in a target 
heart rate zone, with an exercise target of 60 minutes in weeks 1 and 2, 90 minutes in weeks 
3 and 4, 120 minutes in weeks 5 through 8, and 180 minutes in weeks 9 through 12. Target 
heart rate zone was calculated using the heart rate reserve (HRR) method for moderate 
activity levels as described by the American College of Sports Medicine (ACSM), which 
uses an intensity factor of 40-85% of the maximal heart rate achieved during the IMSWT. 
Exercise coaches contacted participants weekly by phone, text, or email to discuss 

strategies for reaching exercise minute goals and provide personalized feedback regarding 
exercise motivations and barriers. Physical activity was participant-determined and based 
on individual preferences, lifestyle, and resource availability.  
 
The control group received standard-of-care instructions regarding exercise and instruction 
on how to access beamfeelgood, an online repository of exercise videos available free of 
charge for PwCF. 
 
Outcome Measures 
 
The IMSWT was used as a surrogate for CR-ﬁtness as it has shown construct validity and 
predictive value for VO2max in adult CF patients. Testing was conducted according to the 
protocol outlined by Singh et al. Distance and maximal heart rate were collected at the end 
of the IMSWT. 
 
Adherence to exercise was calculated as the number of exercise minutes completed in the 
target heart rate zone each week/weekly target exercise minutes. Participants were 
considered to be adherent if they completed ≥70% of weekly exercise minutes for ≥70% of 
the 12-week intervention. 
 
Spirometry was obtained from TUKHS CF outpatient clinic. Forced expiratory ﬂow in one 
second (FEV1) was collected from TUKHS electronic medical record. FEV1 is expressed as 
%predicted (ppFEV1) using NHANES III spirometric reference ranges.  
 
The CFQ-R is a valid and reliable self-administered questionnaire composed of 44 items on 
12 generic and disease-speciﬁc domains and is used to assess health-related quality of life 
(HrQoL) in adults with CF. (citation) Overall CFQ-R score and each domain score were 
collected. 
 
The Barriers to Physical Activity questionnaire assesses barriers to participating in physical 
activity and asks participants to rank 15 items on a 5-point Likert scale from “never” to 
“very often” limiting physical activity. Overall barrier score and each item score were 
collected. 
 
Xe-MRI was used to measure ventilation and gas exchange. Xe-MRI was completed prior to 
the IMSWT for all study participants by a minimum of 30 minutes. Isotopically enriched 
(90% 129Xe) xenon gas (Linde Specialty Gases) was polarized to >25% using a Polarean 9820 
xenon hyperpolarizer (Polarean Imaging Plc., Durham, NC). The total dose volume delivered 
to participants was equal to 20% of FVC measured at the baseline study visit. Participants 
were imaged using a 3T Skyra MRI scanner (Siemens, Erlangen, Germany) using a ﬂexible 
transmit/receive 129Xe vest coil (Clinical MR Solutions, LLC, Brookﬁeld, WI). Calibration 
data was analyzed in real-time using a home-built MATLAB (version 2020A, MathWorks, 
Natick MA) program and the outputs used for subsequent imaging. Following calibration, 
every participant was imaged using 3D ventilation imaging. Within the same breath, a 

geometry-matched 1H anatomic image set was acquired to be used for image 
quantiﬁcation.  
 
Xe-MRI images were quantiﬁed using an automated pipeline to quantify ventilation defect 
percent (VDP). VDP was calculated using the mean anchored linear binning approach with 
a threshold of 60%. VDP was an exploratory endpoint for this study. 
 
Data Analysis 
 
To achieve 80% power at an α level of 0.05 (two-sided), 12 participants were needed in 
each group to detect an emect size of 1.2. A target enrollment of 15 per group (n=30 total) 
was set to account for attrition. 
 
Data is presented as mean ± SD, categorical data is presented as a percentage. Baseline 
between group dimerences were analyzed with a Wilcoxon Mann-Whitney test for 
continuous variables and a Fisher’s exact test for categorical variables, as appropriate. No 
between group dimerences were found for demographic or baseline measures. Group 
dimerences for all outcome measures were assessed using a Wilcoxon Mann-Whitney test. 
An intention-to-treat approach was used for participant baseline characteristics. 
Participants with missing post-intervention data were excluded from group dimerence 
analyses. 
 
All statistical analyses were performed using SAS v9.4. All comparisons were two-sided 
with the level of signiﬁcance set at p < 0.05.