The goal of XFIT study is to measure the safety of an 8-week telehealth-delivered exercise and behavioral training program to treat frailty in lung transplant candidates in their own home. The main questions XFIT aims to answer are:

• Is XFIT safe?
• Is XFIT feasible and acceptable by participants?
• Is XFIT effective in improving frailty and physical function as reflected in patient-reported outcomes.

Participants will:

- Participate in the 8-week XFIT program or enhanced standard of care

We will randomize 70 patients who reflect the diversity and spectrum of illness seen in the general lung transplant candidate population to either XFIT or enhanced standard of care. An interventionalist with expertise in exercise physiology and remote interventions will deliver 8 weekly sessions using video-conference software in participants' homes. These sessions feature one-on-one exercise training and targeting of behavioral barriers to optimizing physical activity using motivational interviewing principles. Establishing safety is our primary outcome. We will secondarily establish feasibility and acceptability, and explore responsiveness six-minute walk distance, frailty, Patient Reported Outcomes . We anticipate that this first-of-its kind study in solid organ transplantation will establish fundamental safety, feasibility, and accessibility data needed inform larger scale interventions.

Group 1

Inclusion Criteria:

• Age 18 - 65 years
• Lung Transplant Candidates
• Speaks English or Spanish
• ≤ 8LPM O2 on 6MWT
• SPPB score ≤ 10

Exclusion Criteria:

• Lives Alone
• BMI < 18.0 kg/m2
• Engaged in clinical pulmonary rehabilitation program
• Severe pHTN (RHC mPAP ≥ 30 mmHg or TTE PASP ≥ 60mmHg or moderately/severely reduced RV systolic function on TTE
• Deemed unsafe by site PI

Group 2

Inclusion Criteria:

• Age 18 - 75 years
• Speaks English or Spanish
• ≤ 15LPM O2 on 6MWT
• SPPB score ≤ 10

Exclusion Criteria:

• Lives Alone
• BMI < 18.0 kg/m2
• Engaged in clinical pulmonary rehabilitation program
• Severely reduced RV systolic function on TTE
• Deemed unsafe by site PI

An anonymized dataset with key study-related data will be made available to investigators upon request one-year after the publication of the primary study findings. Investigators will be able to make requests through Drs. Singer and Smith, who can facilitate such data management tasks. In addition, we will plan to provide a complete, anonymized dataset for deposition into online data repositories within three years of publication of our primary findings, for use in subsequent follow-up analyses or meta-analytic studies. We will also make annotated statistical analytical code available for public usage, in order to increase reproducibility of findings for future studies. We will also make available our final protocol. These data will be available in an online data repository for as long as the repository is able to host them. They will also be available for request from Drs. Singer and Smith.

As detailed above. The trial is expected to run from July 2026 to June 2029.

As above.