Kidney Disease Clinical Trial
Official title:
Safety and Efficacy of Tetrahydrobiopterin in Patients With Chronic Kidney Disease (CKD) and Albuminuria: An Open-Label Pilot Study
Verified date | January 2013 |
Source | University of Michigan |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Institutional Review Board |
Study type | Interventional |
Patients with chronic kidney disease and albuminuria are at increased risk of developing
cardiovascular disease which is often associated with hypertension, left ventricular
hypertrophy, endothelial dysfunction and increased generation of reactive oxygen species
(ROS). These patients also manifest a decrease in nitric oxide availability which is thought
to play an important role in their progressive vascular disease.
Tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide
synthase(eNOS), an important regulator of nitric oxide (NO) and that is a key mediator of
endothelial dysfunction. Changes in nitric oxide availability are believed to contribute to
endothelial dysfunction seen in chronic kidney disease and common cardiovascular disease
states. 6R-tetrahydrobiopterin (6R-BH4 or sapropterin dihydrochloride) is an investigational
oral drug that is being evaluated to determine whether it will restore NO availability,
leading to beneficial effects on vascular function and ultimately positive clinical outcomes
in patients with chronic kidney disease. The primary endpoint in this study is the level of
albuminuria, an easily measured marker that has served as a predictor of kidney disease
progression. If 6R-BH4 reduces albuminuria in patients with kidney disease, it may have
implications to slow the disease progression as well as decreased risk of cardiovascular
disease.
Status | Active, not recruiting |
Enrollment | 40 |
Est. completion date | April 2013 |
Est. primary completion date | September 2008 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Patients with controlled hypertension (BP less than 150/90 mmHg) using standard antihypertensive medications. - Stable CKD (eGFR 40-90 ml/min/173m2 by the abbreviated (4-variable) MDRD equation and with a rate of decline of eGFR no greater than 1ml/min/1.73m2 per month over the prior 3 months with albuminuria (urine albumin excretion in the 24-hr urine sample of between 300-3000mg). - No concomitant use with: - Vitamin C supplements - Multivitamins containing vitamin C - Any other dietary supplements, nutraceuticals, or other over-the-counter products containing vitamin C - Vitamin E containing supplements - Concurrently taking study approved antihypertensive medications at a stable dose for at least 3 months prior to screening. - Sexually active subjects must be willing and able to use an acceptable method of contraception - Females of childbearing potential must have a negative pregnancy test at screening. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy. Exclusion Criteria: - Uncontrolled hypertension with BP greater than 150/90 or with frequent changes to antihypertensive regimen during the last 3 months - Concurrent disease or condition that would interfere with study participation or safety, such as bleeding disorders, history of syncope or vertigo; severe gastroesophageal reflux disease (GERD) or gastric ulcers; heart failure; symptomatic coronary or peripheral vascular disease; arrhythmia; serious neurologic disorders, including seizures; or organ transplant. - Diabetics that are uncontrolled, unstable, newly diagnosed, or have undergone major changes in therapy in the last three months or HbA1C consistently greater than 9.0. - Any severe comorbid condition that would limit life expectancy to less than 6 months. - Advanced stage III CKD or worse , i.e. estimated GFR less than 40 ml/min/1.73m2 (by abbreviated MDRD formula) - History of nephrolithiasis - Patients with albuminuria due to causes other than hypertension and /or diabetes (e.g., SLE) - Hepatic enzyme concentrations greater than 2 times the upper limit of normal. - HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening. - Concomitant treatment with drugs known to inhibit folate metabolism, Levodopa, phosphodiesterase (PDE) 5 inhibitors or PDE 3 inhibitors. - Myocardial infarction, stroke, or surgery within the last 60 days prior to screening. - History of alcohol and/or drug abuse. - Pregnant or breastfeeding at screening, or planning to become pregnant (subject or partner) at any time during the study. - Previous treatment with 6R-BH4 - Has known hypersensitivity to 6R-BH4 or its excipients. - Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of Michigan, GCRC Clinic, C302 Med Inn Bldg, 1500 East Medical Center Dr. | Ann Arbor | Michigan |
Lead Sponsor | Collaborator |
---|---|
University of Michigan | BioMarin Pharmaceutical |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The primary outcome measure is level of albuminuria at 6 and 12 weeks of therapy (based on measurement of 24-hour urine albumin and urine albumin:creatinine ratio). | 16 weeks | Yes | |
Secondary | The primary analyses will be repeated using eGFR and blood pressure as secondary outcome measures. | 16 weeks | Yes |
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