Rhode Island Diastolic Dysfunction - Heart Failure
Information source: Providence VA Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Failure; Cardiovascular Disease
Intervention: Kuvan (Drug)
Phase: N/A
Status: Not yet recruiting
Sponsored by: Providence VA Medical Center Official(s) and/or principal investigator(s): Wen-Chih Wu, MD, MPH, Principal Investigator, Affiliation: Providence VA Medical Center
Overall contact: Sunit-Preet Chaudhry, MD, Phone: 401-273-7100, Ext: 6237, Email: schaudhry2@lifespan.org
Summary
To study the hypothesis that treating patients with underlying diastolic dysfunction with
oral KuvanŽ (BH4, also known as tetrahydrobiopterin) in addition to current best practices
will improve metabolic and echocardiographic diastolic function parameters.
Clinical Details
Official title: Rhode Island Diastolic Dysfunction - Heart Failure
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change from baseline in VO2 consumption
Secondary outcome: Change from baseline in echocardiographic parameters of diastolic dysfunctionChange from baseline in Quality of life measured by Kansas City Cardiomyopathy Questionnaire
Detailed description:
Congestive heart failure carries a significant epidemiologic and economic burden in today's
healthcare system and is associated with increased morbidity and mortality in those
affected.
There are approximately 5 million people in the United States with heart failure, and of
those, nearly half have heart failure with preserved ejection fraction (HFpEF). HFpEF, also
referred to as diastolic heart failure, is a clinical syndrome characterized by prolonged
relaxation of the myocardium resulting in symptoms including dyspnea, edema, fatigue, and
decreased exercise tolerance, which are clinically indistinguishable from the presentation
of heart failure with reduced ejection fraction (HFrEF). The underlying mechanisms in
diastolic dysfunction are not clearly elucidated, making targeted therapy a challenge. There
are currently no FDA approved treatments for this syndrome, and multiple clinical trials
have demonstrated that standard treatments for systolic heart failure are ineffective in
treating diastolic dysfunction. One of the proposed underlying mechanisms of diastolic
dysfunction is via the reduction of nitric oxide (NO), an endothelium-derived vasodilator
that regulates blood pressure and regional blood flow. In 2010, Silberman et al. examined
the effect of cardiac oxidation on nitric oxide and found that depletion of
tetrahydrobiopterin (BH4), an essential cofactor in the production of nitric oxide, causes
uncoupling of nitric oxide synthase, impaired relaxation of cardiac myocytes, and leads to
subsequent diastolic dysfunction. The authors further went on to demonstrate that treatment
with BH4 can improve diastolic dysfunction in a hypertensive mouse model as well as in
isolated cardiac myocytes and may play a role in the treatment of HFpEF.
To the investigators' knowledge, the role of BH4 in treating diastolic dysfunction in human
subjects has not been studied.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Male and female U. S. Veteran patients over the age of eighteen, with
echocardiographic findings of >= Grade 2 diastolic dysfunction [as per American
Society of Echocardiography guidelines] and
2. Diagnosis of hypertension, diabetes, or heart failure in medical records.
3. Eligible subjects must be ambulatory (not dependent on any ambulatory assist devices
including cane or walker).
Exclusion Criteria:
1. Any history of documented ejection fraction <50%
2. Significant COPD (defined as oxygen-dependent COPD)
3. Acute coronary syndrome within the past three months defined by EKG changes and
biomarkers of myocardial necrosis (ie. elevated troponin) in the setting of chest
pain or an anginal equivalent)
4. Presence of hypertrophic cardiomyopathy
5. Presence of infiltrative/restrictive cardiomyopathy
6. Echocardiographic evidence of moderate or severe aortic or mitral valve stenosis or
regurgitation
7. Previously diagnosed phenylketonuria
8. End stage renal disease requiring hemodialysis
9. Pre-existing seizure disorder
10. Terminal illness (not including heart failure) with expected survival of one year or
less
11. Females who are pregnant or breastfeeding. All females of child bearing age will
undergo pregnancy testing prior to randomization.
12. Recent hospitalization within three months.
13. Previous Bioprosthetic and/or mechanical aortic or mitral valves
Locations and Contacts
Sunit-Preet Chaudhry, MD, Phone: 401-273-7100, Ext: 6237, Email: schaudhry2@lifespan.org Additional Information
Starting date: January 2015
Last updated: January 28, 2015
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