Exercise Intolerance in Renal Failure

NCT ID: NCT01356966

Last Updated: 2015-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-05-31

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.

Conditions

Kidney Failure, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Tetrahydrobiopterin

Intervention Type: DRUG

Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks

Folate

Intervention Type: DIETARY_SUPPLEMENT

Folate 1 mg daily for 12 weeks

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 placebo pills PO BID for12 weeks

Folate

Intervention Type: DIETARY_SUPPLEMENT

Folate 1 mg daily for 12 weeks

Interventions

Tetrahydrobiopterin

Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks

Intervention Type: DRUG

Placebo

2 placebo pills PO BID for12 weeks

Intervention Type: DRUG

Folate

Folate 1 mg daily for 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Kuvan; Folic Acid

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Jeanie Park

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeanie Park, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital

Atlanta, Georgia, United States

Atlanta VA Medical Center

Decatur, Georgia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26962106 (View on PubMed)

Other Identifiers

K23HL098744

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00019181

Identifier Type: -

Identifier Source: org_study_id