Sympatholysis in Chronic Kidney Disease
Sym-CKD
Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease
1 other identifier
interventional
110
1 country
1
Brief Summary
The purpose of this study is to find out why patients with chronic kidney disease (CKD) have poor exercise capacity and what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 3, 2015
CompletedFirst Posted
Study publicly available on registry
April 8, 2015
CompletedStudy Start
First participant enrolled
June 11, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
March 5, 2025
February 1, 2025
12 years
April 3, 2015
March 3, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Change in muscle oxygenation after exercise/stretching training
Near-infrared spectroscopy (NIRS) will measure and record tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Baseline, Week 12
Change in muscle interstitial pH after exercise/stretching training
Near-infrared spectroscopy (NIRS) will give an estimation of the pH levels within the muscle interstitial space. Muscle interstitial pH markedly decreases during exercise, and is often lower than blood pH with a larger intracellular to interstitial pH gradient. CKD patients may have less ability to buffer pH changes in the interstitial space during exercise. Bicarbonate supplementation may improve muscle interstitial buffering capacity during exercise, and prevent exaggerated reductions in muscle interstitial pH during exercise.
Baseline, Week 12
Change in venoconstriction after exercise/stretching training
Dorsal hand vein model will be used to assess vascular alpha-1 adrenergic responsiveness by measuring the degree of venous constriction in response to varying dosages of local phenylephrine (PE) infusion.
Baseline, Week 12
Secondary Outcomes (3)
Change in Functional Sympatholysis
Baseline, 30 minutes
Change in muscle interstitial pH after handgrip exercise
Baseline, 30 minutes
Change in Venoconstriction after Phenylephrine
Baseline, 30 minutes
Study Arms (5)
Exercise Training plus Sodium Bicarbonate
ACTIVE COMPARATORSubjects with CKD will undergo exercise training on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each exercise session three times a week.
Exercise Training plus Placebo
ACTIVE COMPARATORSubjects with CKD will undergo exercise training on a stationary bicycle,for 20-45 minutes, 3 times per week, for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Control to Exercise (Stretching) plus Sodium Bicarbonate
ACTIVE COMPARATORSubjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 1300-2600 mg (2-4 pills) of sodium bicarbonate prior to each stretching session three times a week.
Control to Exercise (Stretching) plus Placebo
PLACEBO COMPARATORSubjects with CKD will undergo progressive whole body stretching and toning exercises 3 times a week for 20-45 minutes for 6-12 weeks. Additionally, subjects will take 2-4 placebo tablets prior to each exercise session three times a week.
Healthy Control
NO INTERVENTIONHealthy subjects without CKD will not receive any interventions.
Interventions
Sodium bicarbonate tablet is 650 mg for one tablet. Oral sodium bicarbonate will be given out as 1300mg-2600mg (2-4 pills) prior to each exercise or stretching session. Serum bicarbonate measurements will be monitored throughout the study (at 2 weeks, then every 2-4 weeks thereafter), and bicarbonate dosages will be adjusted to avoid metabolic alkalosis (serum bicarbonate \> 30).
2-4 placebo pills will be given out prior to each exercise or stretching session.
Exercise training consists of riding a stationary bicycle for 20-45 minutes, 3 times per week, supervised by trained exercise specialists, for 6-12 weeks. The exercise program will follow the guidelines provided by the American College of Sports Medicine (ACSM) for optimizing cardiovascular fitness. Exercise intensity will begin at low levels (50 percent of resting heart rate) and increase to no greater than 80 percent of resting heart rate. Exercise time will progress, depending on subject's progress, from 20 minutes per session at first, to a maximum of 45 minutes. Trained staff members will give instructions throughout each exercise session. Before beginning each exercise session, subjects will be instructed on a warm-up focusing on preparing the legs for activity.
Stretching exercise will consist of muscle stretching and toning for 20-45 minutes, 3 times per week, supervised by trained exercise specialists, for 6-12 weeks. Trained staff members will guide subjects with the stretching exercises, and activities are designed to increase flexibility and range of motion. Before beginning each stretching exercise session, subjects will be instructed to warm-up.
Eligibility Criteria
You may qualify if:
- Veterans with Stages III and IV Chronic Kidney Disease (CKD)
- Kidney transplant recipients with varying degrees of kidney function
- Veterans 18-75 years old, without kidney disease, as study controls
- Exercise less than 20 minutes twice per week
- Willing and able to cooperate with the protocol
You may not qualify if:
- Severe CKD (estimated glomerular filtration rate (eGFR) \< 15 cc/minute)
- Metabolic alkalosis (serum bicarbonate \> 28 meq/L)
- Ongoing drug or alcohol abuse
- Diabetic neuropathy
- Any serious systemic disease that might influence survival
- Severe anemia with hemoglobin (Hbg) level \< 10 g/dL
- Clinical evidence of congestive heart failure or ejection fraction below 35%
- Symptomatic heart disease determined by prior electrocardiogram, stress test, and/or history
- Treatment with central alpha agonists (clonidine)
- Uncontrolled hypertension with blood pressure (BP) greater than 170/100 mmHg
- Low blood pressure with BP less than 100/50 mmHg
- Pregnancy or plans to become pregnant
- Current treatment with monoamine oxidase inhibitors (MAOIs)
- Inability to exercise on a stationary bicycle
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Emory Universitylead
Study Sites (1)
Atlanta VA Medical Center
Decatur, Georgia, 30033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jeanie Park, MD
Emory University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
April 3, 2015
First Posted
April 8, 2015
Study Start
June 11, 2015
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
March 5, 2025
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will not share