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NCT Number: NCT02411773

Sympatholysis in Chronic Kidney Disease

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).

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Key information

Conditions

Chronic Kidney Disease Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location status: Recruiting

Location contact

Dana DaCosta

CONTACT

[email protected]

404-727-7762

Jeanie Park, MD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

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

Treatment and study plan

Sodium bicarbonate

Drug

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

Drug

2-4 placebo pills will be given out prior to each exercise or stretching session.

Exercise Training

Behavioral

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)

Behavioral

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 outcomes

  1. Change in muscle oxygenation after exercise/stretching training

    Time frame: Baseline, Week 12

    Near-infrared spectroscopy (NIRS) will measure and record tissue oxyhemoglobin, deoxyhemoglobin, and total hemoglobin.

  2. Change in muscle interstitial pH after exercise/stretching training

    Time frame: Baseline, Week 12

    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.

  3. Change in venoconstriction after exercise/stretching training

    Time frame: Baseline, Week 12

    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 outcomes

  1. Change in Functional Sympatholysis

    Time frame: Baseline, 30 minutes

    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.

  2. Change in muscle interstitial pH after handgrip exercise

    Time frame: Baseline, 30 minutes

    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.

  3. Change in Venoconstriction after Phenylephrine

    Time frame: Baseline, 30 minutes

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Dana DaCosta

CONTACT

[email protected]

404-727-7762

Jeanie Park, MD

CONTACT

404-321-6111 ext. 207070

Sponsors and collaborators

Lead sponsor

Emory University

Other

Registry information

Official study title

Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease

Acronym: Sym-CKD

Important dates

Study start
2015
Primary completion
2027
Study completion
2027
First posted
Apr 8, 2015
Registry last updated
May 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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