Exercise Intolerance in Renal Failure (EIRF)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Jeanie Park, Emory University
ClinicalTrials.gov Identifier:
NCT01356966
First received: May 18, 2011
Last updated: May 29, 2015
Last verified: May 2015
  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
Drug: Placebo
Dietary Supplement: 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:
  • Change in Resting Muscle Sympathetic Nerve Activity (MSNA) [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Mean Central Augmentation Index (AIx) [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.

  • Change in Heart-rate-corrected Augmentation Index (AIx) [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
    The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.


Enrollment: 74
Study Start Date: May 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tetrahydrobiopterin + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily
Drug: Tetrahydrobiopterin
Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks
Other Name: Kuvan
Dietary Supplement: Folate
Folate 1 mg daily for 12 weeks
Other Name: Folic Acid
Placebo Comparator: Placebo + Folate
Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily
Drug: Placebo
2 placebo pills PO BID for12 weeks
Dietary Supplement: Folate
Folate 1 mg daily for 12 weeks
Other Name: Folic Acid

  Eligibility

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

Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
Atlanta VA Medical Center
Decatur, Georgia, United States, 30033
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
Results First Received: May 11, 2015
Last Updated: May 29, 2015
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 July 30, 2015