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NCT Number: NCT01356966

Exercise Intolerance in 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.

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Key information

Conditions

Kidney Failure, Chronic Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Emory University Hospital, Atlanta, Georgia, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Treatment and study plan

Tetrahydrobiopterin

Drug

Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks

Other names: Kuvan

Placebo

Drug

2 placebo pills PO BID for12 weeks

Folate

Dietary Supplement

Folate 1 mg daily for 12 weeks

Other names: Folic Acid

Primary outcomes

  1. Change in Resting Muscle Sympathetic Nerve Activity (MSNA)

    Time frame: Baseline, 12 weeks

Secondary outcomes

  1. 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.

  2. 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.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

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

Registry information

Official study title

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

Acronym: EIRF

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
May 20, 2011
Registry last updated
Jun 1, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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