Clinical trial NCT01356966: Exercise Intolerance in Renal Failure
Official title: The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Failure, Chronic
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-05-20
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.


Eligibility criteria: Inclusion Criteria:

* chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise

  1. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR\>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
* willing and able to cooperate with the protocol
* CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
* controls will be matched for age, gender, race, and hypertensive status.

Exclusion Criteria:

* severe CKD (eGFR\<30 cc/minute)
* drug or alcohol abuse
* diabetes
* any serious systemic disease that might influence survival
* severe anemia with hgb level \<10 g/dL
* clinical evidence of congestive heart failure or ejection fraction below 35%
* any history of past myocardial infarction or cerebrovascular accident
* symptomatic heart disease determined by electrocardiogram, stress test, and/or history
* treatment with central alpha agonists
* uncontrolled hypertension with BP greater than 160/90 mm Hg
* low blood pressure with BP less than 110/60
* history of nephrolithiasis
* pregnancy or plans to become pregnant
* treatment with vitamin C within the past 3 months
* hepatic enzyme concentrations greater than 2 times the upper limit of normal
* HIV infection
* surgery within the past 3 months
* previous treatment with BH4
* known hypersensitivity to BH4
* any condition that places the participant at high risk of poor adherence or poor follow-up
* patients must be willing to use an acceptable method of contraception if of childbearing age

Primary outcomes:
measure: Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change in Mean Central Augmentation Index (AIx)
timeFrame: Baseline, 12 weeks
measure: Change in Heart-rate-corrected Augmentation Index (AIx)
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
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:
citation: Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9.