Sympatholysis in Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

— Sym-CKD  

Official title:

Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02411773
• Other study ID #: IRB00078214
• Status: Recruiting
• Phase: Phase 1
• Start date: June 11, 2015
• Est. completion date: June 2027

Study information

• Verified date: September 2023
• Source: Emory University
• Contact: Dana DaCosta
• Phone: 404-727-7762
• Email: drdacos[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: June 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Sodium Bicarbonate
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).
• Placebo
2-4 placebo pills will be given out prior to each exercise or stretching session.

Behavioral:
• Exercise Training
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.
• Control to Exercise (Stretching)
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.

Locations

Country	Name	City	State
United States	Atlanta VA Medical Center	Decatur	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	Baseline, 30 minutes
Secondary	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.	Baseline, 30 minutes
Secondary	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.	Baseline, 30 minutes