Mechanisms of Muscle Blood Flow Dysregulation and Exercise Intolerance in Chronic Kidney Disease

March 19, 2021 updated by: Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
Patients with chronic kidney disease (CKD) experience fatigue and exercise intolerance. Increased oxidative stress in CKD may be a contributing factor. The role of impaired muscle blood flow regulation has not been fully explored. The investigators hypothesize that functional sympatholysis is exaggerated in CKD and this is associated with increased oxidative stress. The investigators also hypothesize that exercise training will improve functional sympatholysis and oxidative stress

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Progressive muscle weakness and premature fatigue are characterize the condition of chronic kidney disease (CKD) which can be very debilitating. Mechanisms underlying exercise intolerance in CKD is not completely understood. Previous studies have demonstrated impaired skeletal muscle vasodilation during exercise in CKD patients, which may contribute to exercise intolerance. Normally, there is blunting of sympathetic mediated vasoconstriction in exercising muscle to allow for steady blood supply to exercising muscles. This phenomenon is called functional sympatholysis. Functional sympatholysis is impaired by increases in reactive oxygen specie and may be impaired in CKD.

Experiments will be performed on 2 groups of subjects 1) Normal kidney function (eGFR>90) 2) Stage 2-3 CKD (eGFR 30-89). VAsoactive medications will be held for 72 hours before study. All participants will attend a baseline study visit, which will include a physical examination, a medical history review, vital sign measurements, and blood collection. Muscle nerve activity and muscle oxygenation will be measured while the subjects perform hand grip exercise at 30% maximum voluntary contraction with and without lower body negative pressure (- 20 mmHg). Muscle blood flow will be measured before and after hand grip exercises. CKD subjects will then be randomized to exercise training (to squeeze a tennis ball repeatedly for at least 30 min/day) or no exercise training for 28 days. Procedures in baseline visit will be repeated followed by cross over to alternate group for 28 days followed by repeat of baseline procedures. Blood flow, muscle oxygenation and muscle nerve activity will be compared between CKD and normal subjects as well as before and after exercise training for CKD subjects.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Normotensive adults
  • CKD 2-3

Exclusion Criteria:

  • Blood Pressure ≥140/90
  • eGFR >60ml/min/1.73 m2 or eGFR <30ml/min/1.73 m2
  • Any evidence of cardiopulmonary disease, left ventricular hypertrophy or systolic dysfunction by echocardiography.
  • Diabetes mellitus or other systemic illness
  • Pregnancy
  • Any history of substance abuse or current cigarette use
  • Any history of psychiatric illness
  • History of malignancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exercise training followed by no exercise training
CKD subjects will be randomized to exercise training (to squeeze a tennis ball repeatedly for at least 30 min/day) or no exercise training for 28 days. Procedures in baseline visit will be repeated followed by cross over to alternate group for 28 days followed by repeat of baseline procedures.
Behavioral: Forearm exercise training
Subjects will be asked to squeeze a tennis ball repeatedly for at least 30 min/day for 28 days at an approximate rate of 20 squeezes/min.
Experimental: No exercise training followed by exercise training
CKD subjects will be randomized to exercise training (to squeeze a tennis ball repeatedly for at least 30 min/day) or no exercise training for 28 days. Procedures in baseline visit will be repeated followed by cross over to alternate group for 28 days followed by repeat of baseline procedures.
Behavioral: Forearm exercise training
Subjects will be asked to squeeze a tennis ball repeatedly for at least 30 min/day for 28 days at an approximate rate of 20 squeezes/min.
No Intervention: Normal Control
Control subjects without CKD will undergo baseline assessment as above.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in muscle oxygenation
Time Frame: After 28 days
Tissue oxygenation will be recorded using Near-infrared spectroscopy (NIRS)
After 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Forearm vascular conductance (FVC)
Time Frame: After 28 days
Doppler ultrasonography to measure blood flow
After 28 days
Change in plasma isoprostanes
Time Frame: After 28 days
Plasma isoprostanes will be used as a measure of oxidative stress
After 28 days
Change in muscle sympathetic nerve activity (MSNA)
Time Frame: After 28 days
MSNA will be measured using tiny tungsten wire inserted into the common peroneal nerve below fibular head.
After 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

March 18, 2021

Study Completion (Actual)

March 18, 2021

Study Registration Dates

First Submitted

January 8, 2016

First Submitted That Met QC Criteria

January 26, 2016

First Posted (Estimate)

January 27, 2016

Study Record Updates

Last Update Posted (Actual)

March 23, 2021

Last Update Submitted That Met QC Criteria

March 19, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 092015-005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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