Rhode Island Diastolic Dysfunction - Heart Failure

NCT02353312 | Completed Results

• 1 other identifier: 2014-051
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Cardiovascular Disease

Keywords

Diastolic; Biopterin; Therapeutic Use; Drug Therapy; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Oxygen Consumption During Maximal Bike Exercise

  The change from baseline in oxygen consumption during maximal bike exercise. This was measured using cardiopulmonary exercise tress test (CPET), recorded in milliliters per kilogram per minute (mL/kg/min). Higher oxygen consumption scores indicate better aerobic capacity and cardiovascular function. An increase in oxygen consumption from baseline to post-intervention signifies an improvement in these areas. Conversely, a decrease would indicate a decline in aerobic capacity and cardiovascular health.

  Baseline (period 0), 3 mos (period 1), 6 mos (period 2)

Study Arms (2)

Initial Intervention Arm

EXPERIMENTAL

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

Drug: Kuvan

Delayed Intervention Arm

ACTIVE COMPARATOR

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

Drug: Kuvan

Interventions

Kuvan DRUG

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.

Also known as: sapropterin dihydrochloride

Delayed Intervention Arm; Initial Intervention Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Providence VA Medical Center: lead
• BioMarin Pharmaceutical: collaborator
• Lifespan: collaborator

Study Sites (1)

Providence VAMC

Providence, Rhode Island, 02908, United States

Location

MeSH Terms

Conditions

Heart Failure; Cardiovascular Diseases; Heart Murmurs

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Heart Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Incomplete or missing data for only seven participants leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Wen-Chih Wu, MD
• Organization: Providence VA Medical Center

wen-chih.wu@va.gov

4012737100

Study Officials

• Wen-Chih Wu, MD, MPH

  Providence VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Cardiologist

Study Record Dates

• First Submitted: December 29, 2014
• First Posted: February 2, 2015
• Study Start: March 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-07

Locations

US (1)