Ignite Creation Date:
2025-12-24 @ 4:32 PM
Ignite Modification Date:
2025-12-28 @ 9:50 AM
Study NCT ID:
NCT01356966
Status:
COMPLETED
Last Update Posted:
2015-06-01
First Post:
2011-05-18
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Exercise Intolerance in Renal Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007676', 'term': 'Kidney Failure, Chronic'}], 'ancestors': [{'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C003402', 'term': 'sapropterin'}, {'id': 'D005492', 'term': 'Folic Acid'}], 'ancestors': [{'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jeanie.park@emory.edu', 'phone': '404-727-1386', 'title': 'Dr. Jeanie Park', 'organization': 'Emory University'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily', 'otherNumAtRisk': 18, 'otherNumAffected': 2, 'seriousNumAtRisk': 18, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily', 'otherNumAtRisk': 14, 'otherNumAffected': 2, 'seriousNumAtRisk': 14, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders'}, {'term': 'Dysgeusia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Acute Kidney Injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders'}, {'term': 'Eye injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Resting Muscle Sympathetic Nerve Activity (MSNA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily'}, {'id': 'OG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily'}], 'classes': [{'categories': [{'measurements': [{'value': '-7.5', 'spread': '2.1', 'groupId': 'OG000'}, {'value': '3.2', 'spread': '1.3', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, 12 weeks', 'unitOfMeasure': 'bursts/minute', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Two subjects withdrawn from each arm due to adverse events. Additionally, two subjects from the treatment group and one subject from the placebo group were not included in this analysis because an adequate MSNA neurogram was unable to be obtained at the end of the study.'}, {'type': 'SECONDARY', 'title': 'Change in Mean Central Augmentation Index (AIx)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily'}, {'id': 'OG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily'}], 'classes': [{'categories': [{'measurements': [{'value': '-5.8', 'spread': '2.0', 'groupId': 'OG000'}, {'value': '1.8', 'spread': '1.7', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, 12 weeks', 'description': 'The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.', 'unitOfMeasure': 'percent', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Heart-rate-corrected Augmentation Index (AIx)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily'}, {'id': 'OG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.2', 'spread': '2.1', 'groupId': 'OG000'}, {'value': '1.1', 'spread': '1.2', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, 12 weeks', 'description': 'The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.', 'unitOfMeasure': 'percent', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily'}, {'id': 'FG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '14'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Subjects were recruited from the Atlanta Veterans Affairs (VA) Medical Center from August 2010 to May 2014.', 'preAssignmentDetails': '42 subjects were withdrawn prior to group assignment. 16 were screen failures, 7 subjects withdrew, and 19 subjects were terminated early.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '32', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily'}, {'id': 'BG001', 'title': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '57.5', 'spread': '1.3', 'groupId': 'BG000'}, {'value': '55.2', 'spread': '2.2', 'groupId': 'BG001'}, {'value': '56.4', 'spread': '1.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '32', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All subjects that were randomized in the study are included in baseline analysis.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 74}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-05', 'completionDateStruct': {'date': '2014-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-05-29', 'studyFirstSubmitDate': '2011-05-18', 'resultsFirstSubmitDate': '2015-05-11', 'studyFirstSubmitQcDate': '2011-05-19', 'lastUpdatePostDateStruct': {'date': '2015-06-01', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2015-05-29', 'studyFirstPostDateStruct': {'date': '2011-05-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-06-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Resting Muscle Sympathetic Nerve Activity (MSNA)', 'timeFrame': 'Baseline, 12 weeks'}], 'secondaryOutcomes': [{'measure': 'Change in Mean Central Augmentation Index (AIx)', 'timeFrame': 'Baseline, 12 weeks', 'description': 'The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.'}, {'measure': 'Change in Heart-rate-corrected Augmentation Index (AIx)', 'timeFrame': 'Baseline, 12 weeks', 'description': 'The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Kidney Failure, Chronic']}, 'referencesModule': {'references': [{'pmid': '26962106', 'type': 'DERIVED', 'citation': 'Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9.'}]}, 'descriptionModule': {'briefSummary': 'Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise\n\n 1\\. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR\\>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.\n* willing and able to cooperate with the protocol\n* CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)\n* controls will be matched for age, gender, race, and hypertensive status.\n\nExclusion Criteria:\n\n* severe CKD (eGFR\\<30 cc/minute)\n* drug or alcohol abuse\n* diabetes\n* any serious systemic disease that might influence survival\n* severe anemia with hgb level \\<10 g/dL\n* clinical evidence of congestive heart failure or ejection fraction below 35%\n* any history of past myocardial infarction or cerebrovascular accident\n* symptomatic heart disease determined by electrocardiogram, stress test, and/or history\n* treatment with central alpha agonists\n* uncontrolled hypertension with BP greater than 160/90 mm Hg\n* low blood pressure with BP less than 110/60\n* history of nephrolithiasis\n* pregnancy or plans to become pregnant\n* treatment with vitamin C within the past 3 months\n* hepatic enzyme concentrations greater than 2 times the upper limit of normal\n* HIV infection\n* surgery within the past 3 months\n* previous treatment with BH4\n* known hypersensitivity to BH4\n* any condition that places the participant at high risk of poor adherence or poor follow-up\n* patients must be willing to use an acceptable method of contraception if of childbearing age'}, 'identificationModule': {'nctId': 'NCT01356966', 'acronym': 'EIRF', 'briefTitle': 'Exercise Intolerance in Renal Failure', 'organization': {'class': 'OTHER', 'fullName': 'Emory University'}, 'officialTitle': 'The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure', 'orgStudyIdInfo': {'id': 'IRB00019181'}, 'secondaryIdInfos': [{'id': 'K23HL098744', 'link': 'https://reporter.nih.gov/quickSearch/K23HL098744', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tetrahydrobiopterin + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily', 'interventionNames': ['Drug: Tetrahydrobiopterin', 'Dietary Supplement: Folate']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo + Folate', 'description': 'Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily', 'interventionNames': ['Drug: Placebo', 'Dietary Supplement: Folate']}], 'interventions': [{'name': 'Tetrahydrobiopterin', 'type': 'DRUG', 'otherNames': ['Kuvan'], 'description': 'Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks', 'armGroupLabels': ['Tetrahydrobiopterin + Folate']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '2 placebo pills PO BID for12 weeks', 'armGroupLabels': ['Placebo + Folate']}, {'name': 'Folate', 'type': 'DIETARY_SUPPLEMENT', 'otherNames': ['Folic Acid'], 'description': 'Folate 1 mg daily for 12 weeks', 'armGroupLabels': ['Placebo + Folate', 'Tetrahydrobiopterin + Folate']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University Hospital', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '30033', 'city': 'Decatur', 'state': 'Georgia', 'country': 'United States', 'facility': 'Atlanta VA Medical Center', 'geoPoint': {'lat': 33.77483, 'lon': -84.29631}}], 'overallOfficials': [{'name': 'Jeanie Park, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Emory University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Emory University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}, {'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Medicine', 'investigatorFullName': 'Jeanie Park', 'investigatorAffiliation': 'Emory University'}}}}