Ignite Creation Date:
2025-12-26 @ 11:09 AM
Ignite Modification Date:
2025-12-26 @ 11:09 AM
Study NCT ID:
NCT02353312
Status:
COMPLETED
Last Update Posted:
2025-07-03
First Post:
2014-12-29
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Rhode Island Diastolic Dysfunction - Heart Failure
Sponsor:
Providence VA Medical Center
Organization:
Study Overview
Official Title:
Rhode Island Diastolic Dysfunction - Heart Failure
Status:
COMPLETED
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RIDD-HF
Brief Summary:
To study the hypothesis that treating patients with underlying diastolic dysfunction with oral Kuvan® (BH4, also known as tetrahydrobiopterin) in addition to current best practices will improve metabolic and echocardiographic diastolic function parameters.
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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: