Exercise to Treat Frailty and Decreased Physical Function in Transplant Candidates

Exercise as an Intervention to Treat Frailty and Decreased Physical Function in Kidney Transplant Candidates

Frailty is a condition characterized by slowness, weakness, low physical activity, wasting, and exhaustion. Frailty increases the risk for adverse outcomes following transplant such as increased length of stay in the hospital, mortality, or graft function. No interventions for frailty are known for patients with renal disease, but exercise programs like pulmonary rehabilitation have been effective in improving frailty in patients with other diseases, such as lung disease. The goal of this study is to test whether exercise will also improve frailty among patients who are waiting for a kidney transplant and who are considered frail or pre-frail.

Study Overview

• Status: Suspended
• Conditions: Frailty; Kidney Transplant
• Intervention / Treatment: Behavioral: Exercise Program

Detailed Description

RECRUITMENT: This study will be conducted at Mayo Clinic in Rochester, MN. Patients over 18 who have chronic kidney disease will be approached for recruitment. Interested patients will go through the informed consent process and, if frailty testing was not completed within the two weeks prior to consent, patients will complete frailty testing. If patients are considered frail or pre-frail, they will be enrolled in the study.

FRAILTY TESTING: Participants will complete the FP, Short Physical Performance Battery (SPPB) and other frailty testing at the beginning of the study, 4 weeks after beginning the intervention, and 8 weeks after beginning the intervention. Frailty testing will include a hand grip strength test, a gait speed test over 15 feet, repeated chair stands, balance testing, and a body composition scan. Participants will also be asked to wear an activity monitor for 5-7 days at each testing point and to complete a set of questionnaires. Height, weight, BMI, skeletal muscle mass, percent body fat, and segmental lean mass will be recorded. Participants with a pacemaker, an implantable cardioverter-defibrillator (ICD), or an automated ICD (AICD) will not be able to complete. At enrollment, participants 55 and older will undergo a submaximal exercise test to rule out significant undiagnosed cardiopulmonary disease (standard entrance criteria for pulmonary rehabilitation).

INTERVENTION: Participants will be asked to complete 2 1-hour exercise sessions per week for 8 weeks (16 total sessions) under the supervision of a licensed respiratory therapist in Rochester, MN on non-dialysis days unless the participant is on daily or near-daily dialysis (e.g. home hemodialysis or peritoneal dialysis). . The exercise sessions will be based on pulmonary rehabilitation and will follow guidelines established by the American Thoracic Society. Exercise sessions will include endurance (treadmill or cycle ergometer), strength, and flexibility training and will be tailored to individual participants.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years or older
• Consenting to research
• CKD (stages 1-5)
• An SPPB score ≤10 or considered frail or pre-frail by FP

Exclusion Criteria:

• Younger than 18 years
• Patients listed for heart or lung transplants
• Terminal illness with a prognosis of less than 6 months
• Significant comorbidities that limit rehabilitation potential including pulmonary disease requiring continuous oxygen supplementation, active angina, critical aortic sclerosis, decompensated heart failure, or known ventricular arrhythmia.
• Kidney transplant candidates without cardiac clearance for transplant
• An SPPB score >10 or not considered frail or pre-frail by FP
• Non-English speaker without availability of adequate interpreter services (safety concern)
• Failure to pass submaximal exercise test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Exercise Program; All participants will attend a 16-session exercise program based on pulmonary rehabilitation and will complete questionnaires and frailty testing.

Behavioral: Exercise Program; Participants will be asked to complete 2 1-hour exercise sessions per week for 8 weeks (16 total sessions) under the supervision of a licensed respiratory therapist on non-dialysis days. The exercise program will be based on pulmonary rehabilitation and will follow guidelines established by the American Thoracic Society. Exercise sessions will include endurance (treadmill or cycle ergometer), strength (weight resistance), and flexibility training. Exercise sessions will be tailored to individual participants, and participant safety will be monitored during each session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Frailty Status	Frailty will be determined by Frailty Phenotype (FP) or Short Physical Performance Battery (SPPB) scores. FP is determined by the presence of 3 or more of the following: slowness (measured by gait speed), exhaustion (measured with the CES-D), weakness (measured by hand grip strength), low physical activity level (measured with the MLTPAQ and activity monitoring), and wasting (measured through self-report or by tracking changes in weight). The SPPB consists of a gait speed test, balance testing, and repeated chair stands. A score less than or equal to 10 will be considered frail.	2 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Grip Strength	Hand grip strength will be measured using a hand-held dynamometer. Frailty is characterized as the lowest 20% by gender and body mass index.	2 Months
Change in Gait Speed	Gait speed will be measured over a distance of 15 feet at the patient's self-selected walking speed. Frailty is characterized as the slowest 20% by gender and height. Results will be prorated for 4 meters for the SPPB score.	2 Months
Change in Exhaustion	Patients will self-report their level of exhaustion using the Center for Epidemiologic Studies Depression Scale (CES-D) which consists of a 4-point scale. Items on the CES-D are scored from minimum to maximum values (1 point to 4 points) which are indicated on the CES-D as "rarely or none of the time," "some or a little of the time," "occasionally or a moderate amount of time," "most or all of the time," respectively. A higher number of points indicates a worse outcome.	2 Months
Change in Activity	Energy expenditure will be measured using an activity monitor worn on the wrist for 5-7 days. Low activity is defined as activity in the lowest 20% (<383 Kcals/week for men or <270 Kcals/week for women). Patients will also self-report their activity level using the MLTPAQ.	2 Months
Wasting	Wasting is defined as a decrease in lean body mass or unintentional weight loss of 10 or more pounds in one year.	2 Months
Change in SPPB Score	The SPPB consists of a gait speed test, repeated chair stands, and balance testing. Lower scores indicate decreased physical function.	2 Months
Change in Quality of Life	Health-related quality of life will be measured using the KDQOL-SF.	2 Months
Post-Transplant Outcomes	The relationship between exercise, frailty status, and post-transplant outcomes will be examined for patients who receive a transplant within 1 year of enrolling in this study. The various outcome measures will be aggregated to indicate mortality rate up to one year post-transplant.	1 Year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Cassie C Kennedy, MD, Mayo Clinic

Publications and helpful links

General Publications

• Lorenz EC, Hickson LJ, Weatherly RM, Thompson KL, Walker HA, Rasmussen JM, Stewart TL, Garrett JK, Amer H, Kennedy CC. Protocolized exercise improves frailty parameters and lower extremity impairment: A promising prehabilitation strategy for kidney transplant candidates. Clin Transplant. 2020 Sep;34(9):e14017. doi: 10.1111/ctr.14017. Epub 2020 Jul 24.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: 17-009722

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