Back to resultsSympatholysis in Chronic Kidney Disease (Sym-CKD)
Primary Purpose
Chronic Kidney Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sodium Bicarbonate
Placebo
Exercise Training
Control to Exercise (Stretching)
Sponsored by
About this trial
This is an interventional basic science trial for Chronic Kidney Disease
Eligibility Criteria
Inclusion Criteria:
- Veterans with Stages III and IV Chronic Kidney Disease (CKD)
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Atlanta VA Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
No Intervention
Arm Label
Exercise Training plus Sodium Bicarbonate
Exercise Training plus Placebo
Control to Exercise (Stretching) plus Sodium Bicarbonate
Control to Exercise (Stretching) plus Placebo
Healthy Control
Arm Description
Subjects 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.
Subjects 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.
Subjects 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.
Subjects 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 subjects without CKD will not receive any interventions.
Outcomes
Primary Outcome Measures
Change in muscle oxygenation after exercise/stretching training
Near-infrared spectroscopy (NIRS) will measure and record tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
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.
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.
Secondary Outcome Measures
Change in Functional Sympatholysis
Functional sympatholysis is determined by measuring the change in forearm oxygenation via near infrared spectroscopy (NIRS), and forearm blood flow and conductance using ultrasound, during sympathetic activation induced by lower body negative pressure (LBNP), at rest and during handgrip exercise. NIRS measures and records tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Change in muscle interstitial pH after handgrip exercise
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.
Change in Venoconstriction after Phenylephrine
Vascular function is measured as venoconstriction after administration of phenylephrine. 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02411773
Brief Title
Sympatholysis in Chronic Kidney Disease
Acronym
Sym-CKD
Official Title
Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 11, 2015 (Actual)
Primary Completion Date
June 2027 (Anticipated)
Study Completion Date
June 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
Detailed Description
Patients with chronic kidney disease (CKD) suffer from exercise intolerance and poor physical capacity which contributes to increased cardiovascular risk in this patient population. Prior studies have shown that CKD patients have an exaggerated increase in blood pressure (BP) during both static and rhythmic exercise. Such abnormal hemodynamic responses to exercise can contribute to poor physical capacity and abnormal muscle blood flow during exercise in these patients. The goals of this project are to investigate the mechanisms and potential therapies targeting the abnormal hemodynamic response during exercise in CKD by examining the roles of impaired vasodilation, and exaggerated vasoconstriction.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Exercise Training plus Sodium Bicarbonate
Arm Type
Active Comparator
Arm Description
Subjects 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.
Arm Title
Exercise Training plus Placebo
Arm Type
Active Comparator
Arm Description
Subjects 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.
Arm Title
Control to Exercise (Stretching) plus Sodium Bicarbonate
Arm Type
Active Comparator
Arm Description
Subjects 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.
Arm Title
Control to Exercise (Stretching) plus Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects 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.
Arm Title
Healthy Control
Arm Type
No Intervention
Arm Description
Healthy subjects without CKD will not receive any interventions.
Intervention Type
Drug
Intervention Name(s)
Sodium Bicarbonate
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
2-4 placebo pills will be given out prior to each exercise or stretching session.
Intervention Type
Behavioral
Intervention Name(s)
Exercise Training
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Control to Exercise (Stretching)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in muscle oxygenation after exercise/stretching training
Description
Near-infrared spectroscopy (NIRS) will measure and record tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Time Frame
Baseline, Week 12
Title
Change in muscle interstitial pH after exercise/stretching training
Description
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.
Time Frame
Baseline, Week 12
Title
Change in venoconstriction after exercise/stretching training
Description
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.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change in Functional Sympatholysis
Description
Functional sympatholysis is determined by measuring the change in forearm oxygenation via near infrared spectroscopy (NIRS), and forearm blood flow and conductance using ultrasound, during sympathetic activation induced by lower body negative pressure (LBNP), at rest and during handgrip exercise. NIRS measures and records tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.
Time Frame
Baseline, 30 minutes
Title
Change in muscle interstitial pH after handgrip exercise
Description
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.
Time Frame
Baseline, 30 minutes
Title
Change in Venoconstriction after Phenylephrine
Description
Vascular function is measured as venoconstriction after administration of phenylephrine. 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.
Time Frame
Baseline, 30 minutes
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Veterans with Stages III and IV Chronic Kidney Disease (CKD)
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dana DaCosta
Phone
404-727-7762
Email
drdacos@emory.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jeanie Park, MD
Phone
404-321-6111
Ext
207070
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeanie Park, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Atlanta VA Medical Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dana DaCosta
Phone
404-727-7762
Email
drdacos@emory.edu
First Name & Middle Initial & Last Name & Degree
Jeanie Park, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Sympatholysis in Chronic Kidney Disease
We'll reach out to this number within 24 hrs