Exercise Intolerance in Renal Failure (EIRF)

May 29, 2015 updated by: Jeanie Park, Emory University

The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
      • Decatur, Georgia, United States, 30033
        • Atlanta VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Kuvan
Dietary supplement: Folate
Folate 1 mg daily for 12 weeks
Other Names:
  • 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
Dietary supplement: Folate
Folate 1 mg daily for 12 weeks
Other Names:
  • Folic Acid
Drug: Placebo
2 placebo pills PO BID for12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
Time Frame: Baseline, 12 weeks
Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mean Central Augmentation Index (AIx)
Time Frame: Baseline, 12 weeks
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.
Baseline, 12 weeks
Change in Heart-rate-corrected Augmentation Index (AIx)
Time Frame: Baseline, 12 weeks
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.
Baseline, 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

May 18, 2011

First Submitted That Met QC Criteria

May 19, 2011

First Posted (Estimate)

May 20, 2011

Study Record Updates

Last Update Posted (Estimate)

June 1, 2015

Last Update Submitted That Met QC Criteria

May 29, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00019181
  • K23HL098744 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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