Rhode Island Diastolic Dysfunction - Heart Failure (RIDD-HF)
Primary Purpose
Heart Failure, Cardiovascular Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Kuvan
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Diastolic, Biopterin, Therapeutic Use, Drug Therapy, Quality of Life
Eligibility Criteria
Inclusion Criteria:
- 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
- Diagnosis of hypertension, diabetes, or heart failure in medical records.
- Eligible subjects must be ambulatory (not dependent on any ambulatory assist devices including cane or walker).
Exclusion Criteria:
- Any history of documented ejection fraction <50%
- Significant COPD (defined as oxygen-dependent COPD)
- 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)
- Presence of hypertrophic cardiomyopathy
- Presence of infiltrative/restrictive cardiomyopathy
- Echocardiographic evidence of moderate or severe aortic or mitral valve stenosis or regurgitation
- Previously diagnosed phenylketonuria
- End stage renal disease requiring hemodialysis
- Pre-existing seizure disorder
- Terminal illness (not including heart failure) with expected survival of one year or less
- Females who are pregnant or breastfeeding. All females of child bearing age will undergo pregnancy testing prior to randomization.
- Recent hospitalization within three months.
- Previous Bioprosthetic and/or mechanical aortic or mitral valves
Sites / Locations
- Providence VAMC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Initial Intervention Arm
Delayed Intervention Arm
Arm Description
Kuvan® supplementation in addition to standard care for heart failure for three months. At the end of three months, stop Kuvan®, patients will only receive Standard care for heart failure for another 3 months
Standard care for heart failure for three months. At the end of three months, Starting Kuvan® supplementation in addition to Standard care for heart failure for another 3 months
Outcomes
Primary Outcome Measures
Change from baseline in VO2 consumption
This parameter will be obtained via cardiopulmonary exercise stress testing.
Secondary Outcome Measures
Change from baseline in echocardiographic parameters of diastolic dysfunction
echocardiographic parameters of diastolic dysfunction
Change from baseline in Quality of life measured by Kansas City Cardiomyopathy Questionnaire
Full Information
NCT ID
NCT02353312
First Posted
December 29, 2014
Last Updated
January 28, 2019
Sponsor
Providence VA Medical Center
Collaborators
BioMarin Pharmaceutical, Lifespan
1. Study Identification
Unique Protocol Identification Number
NCT02353312
Brief Title
Rhode Island Diastolic Dysfunction - Heart Failure
Acronym
RIDD-HF
Official Title
Rhode Island Diastolic Dysfunction - Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Providence VA Medical Center
Collaborators
BioMarin Pharmaceutical, Lifespan
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Cardiovascular Disease
Keywords
Diastolic, Biopterin, Therapeutic Use, Drug Therapy, Quality of Life
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Initial Intervention Arm
Arm Type
Experimental
Arm Description
Kuvan® supplementation in addition to standard care for heart failure for three months. At the end of three months, stop Kuvan®, patients will only receive Standard care for heart failure for another 3 months
Arm Title
Delayed Intervention Arm
Arm Type
Active Comparator
Arm Description
Standard care for heart failure for three months. At the end of three months, Starting Kuvan® supplementation in addition to Standard care for heart failure for another 3 months
Intervention Type
Drug
Intervention Name(s)
Kuvan
Other Intervention Name(s)
sapropterin dihydrochloride
Intervention Description
Kuvan® (sapropterin dihydrochloride) will be initiated at 10mg/kg/day with meals for one week. After telephone contact on day 7, assuming no adverse effects are noted, the patient will be instructed to increase their daily dose to 20mg/kg/day with meals for the remainder of the 3 months.
Primary Outcome Measure Information:
Title
Change from baseline in VO2 consumption
Description
This parameter will be obtained via cardiopulmonary exercise stress testing.
Time Frame
3 mos, 6 mos
Secondary Outcome Measure Information:
Title
Change from baseline in echocardiographic parameters of diastolic dysfunction
Description
echocardiographic parameters of diastolic dysfunction
Time Frame
3 mos, 6 mos
Title
Change from baseline in Quality of life measured by Kansas City Cardiomyopathy Questionnaire
Time Frame
3 mos, 6 mos
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Diagnosis of hypertension, diabetes, or heart failure in medical records.
Eligible subjects must be ambulatory (not dependent on any ambulatory assist devices including cane or walker).
Exclusion Criteria:
Any history of documented ejection fraction <50%
Significant COPD (defined as oxygen-dependent COPD)
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)
Presence of hypertrophic cardiomyopathy
Presence of infiltrative/restrictive cardiomyopathy
Echocardiographic evidence of moderate or severe aortic or mitral valve stenosis or regurgitation
Previously diagnosed phenylketonuria
End stage renal disease requiring hemodialysis
Pre-existing seizure disorder
Terminal illness (not including heart failure) with expected survival of one year or less
Females who are pregnant or breastfeeding. All females of child bearing age will undergo pregnancy testing prior to randomization.
Recent hospitalization within three months.
Previous Bioprosthetic and/or mechanical aortic or mitral valves
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Chih Wu, MD, MPH
Organizational Affiliation
Providence VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Providence VAMC
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Rhode Island Diastolic Dysfunction - Heart Failure
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