Sympatholysis in Chronic Kidney Disease

NCT ID: NCT02411773

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-11
• Study Completion Date: 2027-06-30

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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Exercise Training plus Sodium Bicarbonate

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.

Group Type: ACTIVE_COMPARATOR

Sodium Bicarbonate

Intervention Type: 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).

Exercise Training

Intervention Type: 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.

Exercise Training plus Placebo

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

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

Exercise Training

Intervention Type: 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) plus Sodium Bicarbonate

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.

Group Type: ACTIVE_COMPARATOR

Sodium Bicarbonate

Intervention Type: 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).

Control to Exercise (Stretching)

Intervention Type: 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.

Control to Exercise (Stretching) plus Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Control to Exercise (Stretching)

Intervention Type: 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.

Healthy Control

Healthy subjects without CKD will not receive any interventions.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jeanie Park

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeanie Park, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Atlanta VA Medical Center

Decatur, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Dana DaCosta

Role: CONTACT

drdacos@emory.edu

404-727-7762

Jeanie Park, MD

Role: CONTACT

404-321-6111 ext. 207070

Facility Contacts

Dana DaCosta

Role: primary

drdacos@emory.edu

404-727-7762

Other Identifiers

IRB00078214

Identifier Type: -

Identifier Source: org_study_id