Clinical trial NCT02411773: Sympatholysis in Chronic Kidney Disease
Official title: Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Kidney Disease
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-04-08
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in muscle oxygenation after exercise/stretching training
timeFrame: Baseline, Week 12
measure: Change in muscle interstitial pH after exercise/stretching training
timeFrame: Baseline, Week 12
measure: Change in venoconstriction after exercise/stretching training
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change in Functional Sympatholysis
timeFrame: Baseline, 30 minutes
measure: Change in muscle interstitial pH after handgrip exercise
timeFrame: Baseline, 30 minutes
measure: Change in Venoconstriction after Phenylephrine
timeFrame: Baseline, 30 minutes
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlanta VA Medical Center
state: Georgia
Study officials:
affiliation: Emory University
name: Jeanie Park, MD
role: PRINCIPAL_INVESTIGATOR
References: