Ignite Creation Date:
2025-12-26 @ 11:09 AM
Ignite Modification Date:
2026-03-04 @ 11:44 AM
Study NCT ID:
NCT02353312
Status:
COMPLETED
Last Update Posted:
2025-07-03
First Post:
2014-12-29
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Rhode Island Diastolic Dysfunction - Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006337', 'term': 'Heart Murmurs'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C003402', 'term': 'sapropterin'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'wen-chih.wu@va.gov', 'phone': '4012737100', 'title': 'Wen-Chih Wu, MD', 'phoneExt': '16237', 'organization': 'Providence VA Medical Center'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Incomplete or missing data for only seven participants leading to small numbers of subjects analyzed.'}}, 'adverseEventsModule': {'timeFrame': '6 months', 'description': 'There were 28 patients enrolled.', 'eventGroups': [{'id': 'EG000', 'title': 'On Kuvan', '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\n\nKuvan: 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.', 'otherNumAtRisk': 28, 'deathsNumAtRisk': 28, 'otherNumAffected': 28, 'seriousNumAtRisk': 28, 'deathsNumAffected': 0, 'seriousNumAffected': 4}, {'id': 'EG001', 'title': 'Off Kuvan', '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', 'otherNumAtRisk': 28, 'deathsNumAtRisk': 28, 'otherNumAffected': 28, 'seriousNumAtRisk': 28, 'deathsNumAffected': 0, 'seriousNumAffected': 6}], 'otherEvents': [{'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 5, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 3, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Emesis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 20, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 17, 'numAffected': 8}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Rhinorrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 17, 'numAffected': 14}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 8, 'numAffected': 7}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'weight gain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 19, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 16, 'numAffected': 12}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'JVD', 'notes': 'Jugular venous distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Pulmonary crackles', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Peripheral abdominal edema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 34, 'numAffected': 21}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 27, 'numAffected': 16}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Other', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 21, 'numAffected': 15}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 25, 'numAffected': 17}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Hospitalizations', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'ER visit', 'stats': [{'groupId': 'EG000', 'numAtRisk': 28, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 28, 'numEvents': 5, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline in Oxygen Consumption During Maximal Bike Exercise', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'On Kuvan', 'description': 'Kuvan® supplementation in addition to standard care for heart failure in either the first or last three months. 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.'}, {'id': 'OG001', 'title': 'Not on Kuvan', 'description': 'Standard care for heart failure in either the first or last three months.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.45', 'spread': '5.00', 'groupId': 'OG000'}, {'value': '14.18', 'spread': '3.69', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.823', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'EQUIVALENCE', 'nonInferiorityComment': 'Pairwise comparisons of VO2 max means with equal variances between participant on and off treatment.'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (period 0), 3 mos (period 1), 6 mos (period 2)', 'description': '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.', 'unitOfMeasure': 'mL/kg/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All patients who had both baseline and final test.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Kuvan First, Then no Kuvan', '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\n\nKuvan: 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.'}, {'id': 'FG001', 'title': 'No Kuvan First, Then Kuvan', '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\n\nKuvan: 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.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '28', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Kuvan First, Then no Kuvan', '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\n\nKuvan: 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.'}, {'id': 'BG001', 'title': 'No Kuvan First, Then Kuvan', '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\n\nKuvan: 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.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '70.4', 'spread': '9.78', 'groupId': 'BG000'}, {'value': '72.1', 'spread': '5.85', 'groupId': 'BG001'}, {'value': '71.4', 'spread': '8.23', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-09-22', 'size': 374279, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-09-26T15:24', 'hasProtocol': True}, {'date': '2016-11-09', 'size': 170238, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2022-09-26T15:26', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 28}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2018-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-07-01', 'studyFirstSubmitDate': '2014-12-29', 'resultsFirstSubmitDate': '2024-04-23', 'studyFirstSubmitQcDate': '2015-01-28', 'lastUpdatePostDateStruct': {'date': '2025-07-03', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-07-01', 'studyFirstPostDateStruct': {'date': '2015-02-02', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2025-07-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline in Oxygen Consumption During Maximal Bike Exercise', 'timeFrame': 'Baseline (period 0), 3 mos (period 1), 6 mos (period 2)', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Diastolic', 'Biopterin', 'Therapeutic Use', 'Drug Therapy', 'Quality of Life'], 'conditions': ['Heart Failure', 'Cardiovascular Disease']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nThere 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.\n\nTo the investigators' knowledge, the role of BH4 in treating diastolic dysfunction in human subjects has not been studied."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. 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\n2. Diagnosis of hypertension, diabetes, or heart failure in medical records.\n3. Eligible subjects must be ambulatory (not dependent on any ambulatory assist devices including cane or walker).\n\nExclusion Criteria:\n\n1. Any history of documented ejection fraction \\<50%\n2. Significant COPD (defined as oxygen-dependent COPD)\n3. 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)\n4. Presence of hypertrophic cardiomyopathy\n5. Presence of infiltrative/restrictive cardiomyopathy\n6. Echocardiographic evidence of moderate or severe aortic or mitral valve stenosis or regurgitation\n7. Previously diagnosed phenylketonuria\n8. End stage renal disease requiring hemodialysis\n9. Pre-existing seizure disorder\n10. Terminal illness (not including heart failure) with expected survival of one year or less\n11. Females who are pregnant or breastfeeding. All females of child bearing age will undergo pregnancy testing prior to randomization.\n12. Recent hospitalization within three months.\n13. Previous Bioprosthetic and/or mechanical aortic or mitral valves'}, 'identificationModule': {'nctId': 'NCT02353312', 'acronym': 'RIDD-HF', 'briefTitle': 'Rhode Island Diastolic Dysfunction - Heart Failure', 'organization': {'class': 'FED', 'fullName': 'Providence VA Medical Center'}, 'officialTitle': 'Rhode Island Diastolic Dysfunction - Heart Failure', 'orgStudyIdInfo': {'id': '2014-051'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Initial Intervention 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', 'interventionNames': ['Drug: Kuvan']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Delayed Intervention 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', 'interventionNames': ['Drug: Kuvan']}], 'interventions': [{'name': 'Kuvan', 'type': 'DRUG', 'otherNames': ['sapropterin dihydrochloride'], '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.', 'armGroupLabels': ['Delayed Intervention Arm', 'Initial Intervention Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02908', 'city': 'Providence', 'state': 'Rhode Island', 'country': 'United States', 'facility': 'Providence VAMC', 'geoPoint': {'lat': 41.82399, 'lon': -71.41283}}], 'overallOfficials': [{'name': 'Wen-Chih Wu, MD, MPH', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Providence VA Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Providence VA Medical Center', 'class': 'FED'}, 'collaborators': [{'name': 'BioMarin Pharmaceutical', 'class': 'INDUSTRY'}, {'name': 'Lifespan', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Staff Cardiologist', 'investigatorFullName': 'Wen-Chih Wu', 'investigatorAffiliation': 'Providence VA Medical Center'}}}}