Exercise Intolerance in Renal Failure (EIRF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Jeanie Park, Emory University
ClinicalTrials.gov Identifier:
NCT01356966
First received: May 18, 2011
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Kidney Failure, Chronic
Drug: tetrahydrobiopterin + folate
Drug: Placebo with folate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Baseline and Exercise-induced change in muscle sympathetic nerve activity, endothelial function, and oxidative stress [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood pressure [ Time Frame: Baseline, 1-3 week intervals, and at 12 weeks ] [ Designated as safety issue: No ]
  • Renal function [ Time Frame: Baseline, 1-3 week intervals, and at 12 weeks ] [ Designated as safety issue: No ]
  • proteinuria [ Time Frame: Baseline, 1-3 week intervals, and at 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BH4 + Folate Drug: tetrahydrobiopterin + folate
Tetrahydrobiopterin 200 mg BID with folate 1 mg daily for 12 weeks
Placebo Comparator: Placebo + Folate Drug: Placebo with folate
Placebo 2 pills BID with folate 1 mg daily

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patients with chronic kidney disease (Stages I, II, and III) who do not regularly exercise, willing and able to cooperate with the protocol. 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 modified MDRD equation100, or an eGFR>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01356966

Contacts
Contact: Melanie Jefferson, MS 404-321-6111 ext 7040 melanie.l.jefferson@emory.edu

Locations
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Melanie Jefferson, MS    404-321-6111 ext 6135    melanie.l.jefferson@emory.edu   
Principal Investigator: Jeanie Park, MD         
Atlanta VA Medical Center Recruiting
Decatur, Georgia, United States, 30033
Contact: Melanie Jefferson, MS    404-321-6111 ext 7040    melanie.l.jefferson@emory.edu   
Principal Investigator: Jeanie Park, MD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Jeanie Park, MD Emory University
  More Information

No publications provided

Responsible Party: Jeanie Park, Assistant Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT01356966     History of Changes
Other Study ID Numbers: IRB00019181, K23HL098744
Study First Received: May 18, 2011
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Folic Acid
Vitamin B Complex
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on October 23, 2014