Physical Fitness/Training and Inflammatory Immune Responses in Patients With End-stage Renal Disease

Association Between Physical Fitness/Training and Pro-inflammatory/Anti-inflammatory Immune Responses in Patients With End-stage Renal Disease

The end-stage renal disease (ESRD) leading two causes of death are cardiovascular diseases and sepsis. Exercise improves low physical fitness, available research concerning its effect on the pro-/anti-inflammatory immune response is scarce. In the current proposal, physical fitness is classified into cardiopulmonary fitness and muscle fitness. Muscle fitness is further divided into three domains: strength, mass, and oxidative capacity. The 3-year proposal plan to recruit 90 patients with ESRD who receive regular HD for more than 6 months. Every participant will go through 3 phases：control phase、training phase and the maintenance phase (within-subject design). The hypothesis of the proposal is as follows. (I) When cardiopulmonary fitness/muscle fitness drops to a certain level, the inflammatory immune response will rise. The proposal aims to find the best biomarkers and their cut-off points among the various indicators of cardiopulmonary and muscle fitness that reflect immune dysregulation. (II) Other than physical fitness, cyclic aerobic and resistance training improves pro-/anti-inflammatory immune dysregulation. Additionally, three months after cessation of training, a thorough assessment will be performed to examine whether a healthy lifestyle behavior modification has been achieved and whether the beneficial effect of physical fitness and immune regulation induced by the training program is maintained. The goal of each year is as follows. FIRST year: To explore the relationship between cardiopulmonary fitness and pro-/anti-inflammatory immune response in ESRD patients under HD; SECOND year: To explore the relationship between muscle fitness and pro-/anti-inflammatory immune response; THIRD year: To evaluate the effects of cyclic aerobic and resistance training on physical fitness and pro-/anti-inflammatory immunomodulation in ESRD patients under HD.

Study Overview

• Status: Recruiting
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Other: aerobic training by a cycle ergometer and Biodex system 4 pro

Detailed Description

In Taiwan, there are more than 90 thousand patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) island-wide. The leading two causes of death are cardiovascular diseases and sepsis. Though evidence is clear that exercise training in this population is beneficial to fitness、quality of life、morbidity, it is seriously underuse. Poor physical fitness is known to associate with high-leveled systemic inflammation and immune dysregulation but the detailed relationship remains unclear in the ESRD population. Moreover, though exercise improves low physical fitness, available research concerning its effect on the pro-/anti-inflammatory immune response is scarce. In the current proposal, physical fitness is classified into cardiopulmonary fitness and muscle fitness. Muscle fitness is further divided into three domains: strength, mass, and oxidative capacity. The 3-year proposal plan to recruit 90 patients with ESRD who receive regular HD for more than 6 months. Every participant will go through 3 phases：control phase、training phase and the maintenance phase (within-subject design). In the control phase, no exercise education or training will be given to the participants. In the training phase, the participants will receive in-hospital supervised exercise training prior to HD. The training program will last 6 months and about 60 training sessions in total. The training protocol contains cyclic aerobic training in moderate-intensity and high-intensity interval training plus isokinetic resistance training. In the following maintenance phase, home-based exercise training will be educated. The control and maintenance phases are 1-2 and 3 months respectively in duration. Before and after each phase and in the middle of the training phase (5-time points totally), every participant will receive a thorough evaluation as follows: CPET with noninvasive cardiac output monitor, isokinetic strength testing, handgrip strength, muscle oxidative capacity, body composition by dual-energy x-ray absorptiometry, Chinese Kidney Disease and Quality of Life questionnaire and international physical activity questionnaire and blood sampling for pro-/anti-inflammatory markers, including chemokine, cytokine, immune cells, and immuno-regulatory microRNAs, etc. The hypothesis of the proposal is as follows. (I) When cardiopulmonary fitness/muscle fitness drops to a certain level, the inflammatory immune response will rise. The proposal aims to find the best biomarkers and their cut-off points among the various indicators of cardiopulmonary and muscle fitness that reflect immune dysregulation. (II) Other than physical fitness, cyclic aerobic and resistance training improves pro-/anti-inflammatory immune dysregulation. Additionally, three months after cessation of training, a thorough assessment will be performed to examine whether a healthy lifestyle behavior modification has been achieved and whether the beneficial effect of physical fitness and immune regulation induced by the training program is maintained. The goal of each year is as follows. FIRST year: To explore the relationship between cardiopulmonary fitness and pro-/anti-inflammatory immune response in ESRD patients under HD; SECOND year: To explore the relationship between muscle fitness and pro-/anti-inflammatory immune response; THIRD year: To evaluate the effects of cyclic aerobic and resistance training on physical fitness and pro-/anti-inflammatory immunomodulation in ESRD patients under HD.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shu-Chun Huang, MD, PhD; Phone Number: 5156 +88633281200; Email: mr7171@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Shu-Chun Huang, MD, PhD; Phone Number: 5156 +8863281200; Email: mr7171@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• on HD for longer than 6 months
• under the permission of their nephrologist
• adequately dialyzed (most recent Kt/V > 1.2) and stable during dialysis in the past 3 months

Exclusion Criteria:

• occurrence of hyperkalemia in the past 3 months
• comorbid medical, physical, and mental conditions that contraindicate exercise
• unstable cardiac conditions (eg, unstable angina, heart failure or symptomatic severe aortic stenosis, etc.)
• disabling orthopedic and neuromuscular diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: ESRD patients with supervised training; The participants will receive in-hospital supervised exercise training prior to HD	Other: aerobic training by a cycle ergometer and Biodex system 4 pro; cyclic aerobic training in moderate-intensity and high-intensity interval training plus isokinetic resistance training prior to HD. 60 training sessions in 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the association between fitness and immune responses in ESRD patients by cardiopulmonary exercise test	cardiopulmonary exercise test	three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To examine the levels of inflammatory chemokines in the circulation of patients by Luminex assay	Luminex assay	three years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To detect the levels of anti-inflammatory microRNAs in the circulation of patients by qPCR and pro-/anti-inflammatory immunomodulation	qPCR assay training and pro-inflammatory/anti-inflammatory immune responses in ESRD patients under HD (longitudinal design	three years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Shu-Chun Huang, MD, PhD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Anticipated): July 30, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 202000666B0

Drug and device information, study documents

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