Exercise Intolerance in Renal Failure

Kidney Failure, Chronic Clinical Trial

— EIRF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01356966
• Other study ID #: IRB00019181
• Secondary ID: K23HL098744
• Status: Completed
• Phase: Phase 2
• First received: May 18, 2011
• Last updated: May 29, 2015
• Start date: May 2011
• Est. completion date: May 2014

Study information

• Verified date: May 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Tetrahydrobiopterin
Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks
• Placebo
2 placebo pills PO BID for12 weeks

Dietary Supplement:
• Folate
Folate 1 mg daily for 12 weeks

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Atlanta VA Medical Center	Decatur	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Resting Muscle Sympathetic Nerve Activity (MSNA)		Baseline, 12 weeks	No
Secondary	Change in Mean Central Augmentation Index (AIx)	The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (? P) to central pulse pressure and expressed as percent. AIx = (?P/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	No
Secondary	Change in Heart-rate-corrected Augmentation Index (AIx)	The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (? P) to central pulse pressure expressed as a percent. AIx = (?P/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	No