Lung Transplant G0 (LTGO): Improving Self-Management of Exercise After Lung Transplantation
Phase: NA
Conditions: Exercise, Lung Transplantation
Sponsor: University of Pittsburgh

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Study Protocol and Statistical Analysis 
 
 
 
 
 
Official Title: Lung Transplant G0 (LTGO): Improving Self-Management of Exercise 
After Lung Transplantation 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT 03728257 
 
 
 
Protocol Date: 9/21/2024 
 
 
 
 

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Scientific Background 
Lung transplantation is one of the fastest growing solid organ transplant procedures in the United 
States.[1] Over the past four decades, notable progress has been made in the success of lung 
transplantation due to advances in organ preservation, surgical techniques, availability of bridge 
treatments (e.g., ventilator support, extracorporeal membrane oxygenation), and new 
immunosuppressive regimens.[2] According to the most recent report from the International 
Society for Heart and Lung Transplantation (ISHLT), the overall 5-year survival rate for LTR is 
53%.[2] Lung transplantation leads to extended survival and quality of life in persons limited by 
advanced lung disease[3-5] and, therefore, has become an established treatment option.  
 
After transplant, lung function typically returns to near normal levels. [6-8] However, reduced 
physical function and an inactive lifestyle compromise this benefit. Prior to transplant, end-stage 
lung disease reduces ventilatory capacity.[9] Disabling dyspnea limits physical activity and 
exercise, causing low muscle mass and qualitative changes in large exercising skeletal muscle 
groups.[10] Thus, LTR are severely deconditioned when they come to transplant surgery. After 
transplant, skeletal muscle changes persist.[11] Side effects of  
immunosuppressive agents further reduce lean muscle mass, increase fatigue, and decrease 
motivation to stay active.[12] A systematic review of 18 studies evaluating loss of skeletal 
muscle mass, strength and function in LTR reported that quadriceps strength was reduced in the 
pre-transplant period (range, 49%-86% predicted; n = 455 patients), further reduced immediately 
after transplant (51%-72% predicted, n = 126), with variable improvement at 3 months after 
transplant (58%-101% predicted, n = 164).[13]  
 
While improved lung function after transplant has the potential to improve physical function, 
there is consistent evidence of limitations in reaching this goal.[6, 14-16] To promote 
rehabilitation goals, LTR are advised to attend a PR program.[17-19] Whereas post-transplant 
medical management requires following an established protocol, participation in PR is elective to 
LTR’s individual decision. Studies documenting PR outcomes in other populations, [20, 21] 
consistent with our experience, report that PR is underused. It enrolls about a half of those 
referred [20] and loses > 25% of those who enroll to attrition.[21] Attrition of LTR in our PR 
clinic was greater than 50%. Barriers include scheduling and travel requirements,[18] perceptual 
disincentives and, of concern to LTR on immunosuppressive regimens, group participation 
which risks exposure to infection. Further, and of primary interest to this study, we pose that 
characteristics inherent to PR programs impact long-term adherence to exercise in LTR. During 
PR, exercise occurs under close clinician supervision but, afterward, LTR are expected to 
continue exercise unsupervised at home while not feeling confident. Consequently, LTR have 
little opportunity to establish behavior patterns that promote continued, independent self-
management of exercise. Importantly, behavioral strategies, essential to achieve exercise goals 
and sustain self-management of exercise and active lifestyle, are not the main focus of traditional 
PR programs.  
 
Telerehabilitation (TR) offers a flexible and sustainable alternative with the potential to promote 
and sustain self-management of exercise in LTR. Defined as an application of tele-health to 
rehabilitation,[22] TR uses telecommunication and computing technology to assess patients and 
deliver interventions in remote locations.[23-25] RCTs have evaluated TR-focused interventions 
in other populations, e.g., knee arthroplasty, stroke, and supported benefits of TR.[26-28] No 

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RCT has evaluated the use of the TR in LTR nor have exercise interventions for LTR 
incorporated behavioral strategies for self-management of exercise. 
 
Study Objectives 
 
The study aims to evaluate efficacy of a behavioral exercise intervention, Lung Transplant Go 
(LTGO) compared to enhanced usual care (EUC) in improving physical function, physical 
activity and blood pressure (BP) control in lung transplant recipients.  
 
Primary Aim: Evaluate efficacy of LTGO in improving physical function and physical activity 
from baseline to 3 and 6 months post-randomization. 
 
Secondary Aim: Evaluate efficacy of LTGO on BP control from baseline to 3 and 6 months post-
randomization. 
 
 
Study Design & Methods 
 
After completing a baseline assessment, lung transplant recipients (LTRs) were randomized 1:1 
to either the LTGO or Enhanced Usual Care group. To achieve balance between groups for 
known differences in exercise capacity, a blocked randomization scheme stratified by sex, and 
length of transplant-hospital stay (≤2 weeks or >2 weeks) was used as an indicator of hospital-
associated deconditioning. The statistician was responsible for randomization.  
 
 
 
After the start of Covid, all study activities were performed remotely for both groups, including 
intervention delivery, recruitment, consenting, assessment, and data collection. Outcome 
assessors were blinded to group assignments. Data collectors were trained to perform study 
assessments until they demonstrated competency. Quality control checks of inter-rater reliability 
between assessors were repeated every quarter and remediation was instituted to remedy any 
drift from the assessment protocol less than (r = .97). Assessors were trained to abstract data 

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from the electronic health record using established code books. Inter-rater reliability was 
determined between two raters for every 10 records. Data safety and intervention fidelity were 
monitored regularly. Surveys and semi-structured interviews were used to determine the usability 
and acceptability of the LTGO intervention. Performance of all assessments and delivery of 
intervention sessions and phone calls were audio or video-recorded. Intervention fidelity was 
monitored for 10% of phase 1 exercise sessions per subject and all phase 2 phone calls. Data 
safety monitoring (DSM) meetings were held monthly by the PI and PD, and annually by PI, PD 
and medical monitor. 
 
Eligibility Criteria  
Inclusion Criteria: 
• 
18 years of age or older 
->4 weeks after the participant had lung transplant surgery 
• 
Discharged from the hospital after your lung transplant surgery 
• 
MD report of difficulty walking ¼ mile or climbing 10 steps without resting 
• 
Medical monitor approves patient eligibility for participation 
Exclusion Criteria: 
• 
concurrent participation in a formal exercise program, e.g., pulmonary rehabilitation, 
during the active eligible study period with no plans to stop formal exercise 
• 
having other chronic conditions that may severely limit participation in exercise training, 
i.e., cardiac, musculoskeletal or cognitive impairments 
• 
does not have home internet or smart device with Bluetooth capabilities 
• 
medical issue precluding participation 
• 
declining to be asked screening questions, or declining an introduction to the research 
team to hear about research 
• 
greater than 18 months post-transplant hospital discharge (time/scheduling delays, 
transportation issues, etc.) 
 
Protocol changes to primary outcomes due to COVID 
1. Primary Outcome: Physical function-Walking, Change is being assessed from baseline to 3 
months  
* Protocol modification 06-24-2020: since COVID, alternate measures for 6MWT due to 
inability to conduct in-person outcome assessments were the 30 Second Chair Stand Test (see 
primary outcome 5 and 6) and Average Steps per Day  

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2. 
Primary Outcome: Physical function- Walking, Change is being assessed from baseline to 6 
months using Avg Steps per Day 
*Protocol modification 06-24-2020: since COVID, alternate measures for 6MWT due to 
inability to conduct in-person outcome assessments were the 30 Second Chair Stand Test (see 
primary outcome 5 and 6) and Average Steps per Day 
3. 
Primary Outcome: Physical function- Balance-Change is being assessed from baseline to 3 
months using the Berg Balance Scale  
 
4. 
Primary Outcome: Physical function- Balance-Change is being assessed from baseline to 6 
months using the Berg Balance Scale 
 
5. 
Primary Outcome: Physical function- Lower Body Strength-Change is being assessed from 
baseline to 3 months using the 30 Second Chair Stand Test 
 
6. 
Primary Outcome: Physical function- Lower Body Strength-Change is being assessed from 
baseline to 6 months using the 30 Second Chair Stand Test 
 
Primary outcome: Physical function- maximal exercise watts per Kg, Change is being 
assessed from baseline to 3 months during the Cardio Pulmonary Exercise Test (CPET) 
 
*Protocol modification- since COVID, the max ex watts per KG test was excluded from 
outcomes due to inability to conduct in-person outcome assessments and no alternative measure 
was available for the CPET. This modification does not appear in the primary outcomes change 
history.  
 
* Protocol modification-Physical function- Quadriceps Muscle Strength-outcome was never 
assessed as it was deemed redundant with the 30 Second Chair Stand Test. This 
modification does not appear in the primary outcomes change history. 
 
7. 
Primary Outcome: Physical function- Respiratory-related quality of life, Change is being 
assessed from baseline to 3 Months using the St. George Respiratory Questionnaire (SGRQ 
 
8. 
Primary Outcome: Physical function- Respiratory-related quality of life, Change is being 
assessed from baseline to 6 Months using the St. George Respiratory Questionnaire (SGRQ) 
 
9. 
Primary Outcome: Physical Activity-Minutes of Moderate to Vigorous Physical Activity Per 
Day, Change from Baseline to 3 Months using Actigraph 
*Protocol modification 06-24-2020: since COVID, due to inability to conduct in-person 
outcome assessments, the Actigraph or the International Physical Activity Questionnaire-S 
(IPAQ-S) were approved measures of physical activity. The actigraph devices were mailed 
to participants thus preluding the need to administer the IPAQ.  

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10. Primary Outcome: Physical Activity-Minutes of Moderate to Vigorous Physical Activity Per 
Day, Change from Baseline to 6 Months using Actigraph 
*Protocol modification 06-24-2020: since COVID, due to inability to conduct in-person 
outcome assessments, the Actigraph or the International Physical Activity Questionnaire-S 
(IPAQ-S) were approved measures of physical activity. The actigraphs were mailed to 
participants thus preluding the need to administer the IPAQ.  
11.   Secondary outcome: Blood Pressure Control, Change in stage of hypertension from baseline 
to 3 months  
 
12.   Secondary outcome: Blood Pressure Control, Change in stage of hypertension from baseline 
to 6 months  
 
Statistical Considerations 
 
An intent-to-treat (ITT) design was used wherein all participants were analyzed in the groups to 
which they were randomly assigned, regardless of treatment received or protocol deviations. The 
projected sample size was 112 participants a priori to reach a final sample of 80 randomized 
subjects (40 per group) to achieve 80% power to detect an effect size as small as 0.64, α=0.05, 
two-tailed, for measures of the difference between LTGO and EUC groups in change in physical 
function, physical activity, and blood pressure control between baseline and 3 and 6 months.   
 
Phases of data analysis involved an initial screening of data followed by the primary analysis to 
address each specific aim. All the analyses, including exploratory data analysis and linear mixed 
model, will be conducted by using SAS (v. 9.4, SAS Institute, Inc., Cary, NC).  
 
Standard descriptive summaries (e.g., means, standard deviation, percentiles, range) and 
graphical techniques (e.g., histograms, scatter plots) were generated. The distribution of key 
variables was examined to ensure that the proposed modeling techniques were suitable. The 
assumptions underlying planned analysis methods were checked, and appropriate data 
transformation were performed, if necessary. The two groups were compared with respect to 
baseline variables using Student t-test or Mann-Whitney U test for continuous variables; 
categorical variables were compared between two groups by using Chi-square test or Fisher’s 
exact test to ensure that randomization resulted in equal distribution of important variables.