## Protocol Section
### Identification Module
**NCT ID:** NCT06417307

**Brief Title:** Exercise Therapy on Mitochondrial Functions of Lymphocyte in Hemodialysis

**Official Title:** Supervised Exercise Therapy on Mitochondrial Functions of Platelet and Lymphocyte in Patients With End-Stage Renal Disease on Hemodialysis

#### Organization Study ID Info
**ID:** 202002321A3C501
#### Organization
**Class:** OTHER
**Full Name:** Chang Gung Memorial Hospital
### Status Module
#### Completion Date
**Date:** 2024-07-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-07-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-08-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Chang Gung Memorial Hospital

#### Responsible Party

**Investigator Affiliation:** Chang Gung Memorial Hospital

**Investigator Full Name:** Jong-Shyan Wang

**Investigator Title:** Consultant

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** To improve aerobic capacity, muscular function and health-related quality of life in patients with end-stage renal disease (ESRD), regular exercise is recommended. Supervised intradialytic exercise with moderate intensity is an available approach to maintain patients' safety and compliance, and enhance physiological adaptations effectively. The exercise training effects of mitochondrial functions of lymphocyte in ESRD patients, like respiratory capacity, bioenergetic status and thrombosis/immunological regulation remained unclear.

Method: ESRD patients (anticipated n=180) would conduct supervised exercise training therapy for 3 days a week for 6 months in the hospital and 3 months at home. Cardiopulmonary exercise therapy would be performed before and after the intervention. A high resolution respirometer and a flow cytometer are used to determine the oxygen consumption rate/mitochondrial respiration in mitochondria and subtypes of lymphocyte, respectively.

**Detailed Description:** Renal dysfunction results from cardiovascular-related comorbidities or metabolic disorders, accumulating excessive inflammatory products or damage mitochondrial bioenergetics health in platelet and lymphocyte, then lead to chronic kidney disease (CKD) eventually. End-stage renal disease (ESRD) is the highest level of CKD, patients at ESRD stage suffer from severe uremia and renal failure, preparing renal replacement therapy: dialysis.

Hemodialysis (HD) are the most common treatment for ESRD patients, especially in Taiwan, where reports the highest prevalence of HD globally due to related chronic diseases and comprehensive National Health Insurance program. Maintenance (long-term) HD results in physical inactivity and low quality of life; thus, exercise training is recommended to improve physiological adaptations and functional capacity for HD patients. With supervised condition and a safer progression, intradialytic exercise in clinical settings provides low dropout rate and superior compliance.

Mitochondrial dysfunction is one of the concerned issues in ESRD, impaired mitochondria also dysregulate circulating lymphocyte, leading to immunological senescence .

The purposes of the present study are to establish the measurements of mitochondrial functions of platelet and lymphocyte in HD patients, and determine cardiovascular and muscular fitness along with the effects of intradialytic exercise.

### Conditions Module

**Conditions:**

- Hemodialysis Complication

**Keywords:**

- Hemodialysis

- Mitochondria

- Lymphocyte

- Exercise training

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 180

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Moderate intensity continuous cycling training.

**Intervention Names:**

- Behavioral: Supervised exercise training

**Label:** Supervised exercise training

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Recieve no intervention but only maintain daily lifestyle.

**Intervention Names:**

- Behavioral: Control group

**Label:** Control group

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Supervised exercise training

**Description:** Participants perform Intradialytic cycling exercise training in the hospital for 6 months (24 weeks) and 3 months (12 weeks) at home. Exercise prescription: 50-60% maximal workload for 20-30 minutes, including low intensity warm-up and cool down (30% of maximal workload).

**Name:** Supervised exercise training

**Type:** BEHAVIORAL

#### Intervention 2

**Arm Group Labels:**

- Control group

**Description:** Maintain daily lifestyle until the end of the study. Receive no intervention/supplements.

**Name:** Control group

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** Evaluate oxygen consumption rate (oxidative phophorylation/electron transport chain), bioenergetic health index (BHI) in lymphocyte by using a high resolution respirometer.

Evaluate mitochondrial function and subtypes of lymphocyte by using a aflow cytometer.

**Measure:** Mitochondrial function of lymphocyte

**Time Frame:** 9 months

#### Secondary Outcomes

**Description:** ESRD patients performed cardiopulmonary exercise testing (CPET) to assess their aerobic capacity. CPET composed of continuous workload increment of 10 W/min until exhaustion (usually within 8-12 minutes). Oxygen consumption, carbon dioxide production, ventilation, respiratory rate would be recorded.

**Measure:** Cardiopulmonary fitness

**Time Frame:** 9 months

**Description:** We would use a qusionnaire named ESRDkidney disease quality of life-36 (KDQOL-36) to record and scale the qulaity of life in ESRD patients. The content include work status, cognitive funtion, social support, physical functioning and so on.

**Measure:** Quality of life in ESRD patients

**Time Frame:** 9 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* All patients have been receiving hemodialysis and medication at least for 6 weeks, the Kt/V score must be above 1.2 to show that they were stable.

Exclusion Criteria:

* Under 20 years-old, hyperkalemia occurs within 3 month, orthopedic or muscular diseases, other medical, psychological or physiological diseases, pregnancy exercise contraindications.

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** s5492@mail.cgu.edu.tw

**Name:** Jong-Shyan Wang, PhD

**Phone:** +886-3-2118800

**Phone Ext:** 5748

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Taoyuan

**Contacts:**

***Contact 1:***

- **Name:** Jong-Shyan Wang, PhD

- **Role:** CONTACT

**Country:** Taiwan

**Facility:** Chang Gung University

**Status:** RECRUITING

**Zip:** 333

#### Overall Officials

**Official 1:**

**Affiliation:** Chang Gung Memorial Hospital

**Name:** Jong-Shyan Wang, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Sovatzidis A, Chatzinikolaou A, Fatouros IG, Panagoutsos S, Draganidis D, Nikolaidou E, Avloniti A, Michailidis Y, Mantzouridis I, Batrakoulis A, Pasadakis P, Vargemezis V. Intradialytic Cardiovascular Exercise Training Alters Redox Status, Reduces Inflammation and Improves Physical Performance in Patients with Chronic Kidney Disease. Antioxidants (Basel). 2020 Sep 15;9(9):868. doi: 10.3390/antiox9090868.

**PMID:** 32942555

**Citation:** Altintas MM, DiBartolo S, Tadros L, Samelko B, Wasse H. Metabolic Changes in Peripheral Blood Mononuclear Cells Isolated From Patients With End Stage Renal Disease. Front Endocrinol (Lausanne). 2021 Mar 9;12:629239. doi: 10.3389/fendo.2021.629239. eCollection 2021.

**PMID:** 33790861

**Citation:** Deligiannis A, D'Alessandro C, Cupisti A. Exercise training in dialysis patients: impact on cardiovascular and skeletal muscle health. Clin Kidney J. 2021 Jan 11;14(Suppl 2):ii25-ii33. doi: 10.1093/ckj/sfaa273. eCollection 2021 Apr.

**PMID:** 33981417

**Citation:** Chou CH, Fu TC, Tsai HH, Hsu CC, Wang CH, Wang JS. High-intensity interval training enhances mitochondrial bioenergetics of platelets in patients with heart failure. Int J Cardiol. 2019 Jan 1;274:214-220. doi: 10.1016/j.ijcard.2018.07.104. Epub 2018 Jul 27.

**PMID:** 30072155

**Citation:** Lopes LCC, Mota JF, Prestes J, Schincaglia RM, Silva DM, Queiroz NP, Freitas ATVS, Lira FS, Peixoto MDRG. Intradialytic Resistance Training Improves Functional Capacity and Lean Mass Gain in Individuals on Hemodialysis: A Randomized Pilot Trial. Arch Phys Med Rehabil. 2019 Nov;100(11):2151-2158. doi: 10.1016/j.apmr.2019.06.006. Epub 2019 Jul 3.

**PMID:** 31278924

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10699

- Name: Kidney Failure, Chronic

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Browse Branches

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M4854

- Name: Benzocaine

- Relevance: LOW

- As Found: Unknown

- ID: T433

- Name: Tannic Acid

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
