Ignite Creation Date:
2025-12-24 @ 5:25 PM
Ignite Modification Date:
2025-12-28 @ 12:37 PM
Study NCT ID:
NCT01411150
Status:
COMPLETED
Last Update Posted:
2014-02-10
First Post:
2011-08-04
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Premanifest Huntington's Disease: Creatine Safety & Tolerability Extension Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006816', 'term': 'Huntington Disease'}], 'ancestors': [{'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003704', 'term': 'Dementia'}, {'id': 'D002819', 'term': 'Chorea'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D003401', 'term': 'Creatine'}], 'ancestors': [{'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 38}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-01', 'dispFirstSubmitDate': '2014-01-10', 'completionDateStruct': {'date': '2012-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-01-10', 'studyFirstSubmitDate': '2011-08-04', 'dispFirstSubmitQcDate': '2014-01-10', 'studyFirstSubmitQcDate': '2011-08-04', 'dispFirstPostDateStruct': {'date': '2014-02-10', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2014-02-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2011-08-08', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety', 'timeFrame': '12 months', 'description': 'Frequency of adverse events'}, {'measure': 'Tolerability', 'timeFrame': '12 months', 'description': 'Proportion of subjects completing the extension study at given dose level'}], 'secondaryOutcomes': [{'measure': 'Clinical measures', 'timeFrame': '12 months', 'description': "Components of the UHDRS (United Huntington's Disease Rating Scale)"}, {'measure': 'Biological Markers of Disease Progression', 'timeFrame': '12 Months', 'description': "Biological indicators that creatine treatment might affect the progression of HD: plasma levels of creatine, serum levels of 8OH2'dG and 8OHG, magnetic resonance imaging (MRI), morphometric neuroimaging (biomarker of neurodegeneration), metabolomic profiling, and gene expression analysis to assess transcriptional effects of HD and creatine therapy."}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Premanifest', 'At-Risk', "Huntington's Disease", 'HD'], 'conditions': ["Huntington's Disease"]}, 'referencesModule': {'references': [{'pmid': '21611979', 'type': 'BACKGROUND', 'citation': "Rosas HD, Reuter M, Doros G, Lee SY, Triggs T, Malarick K, Fischl B, Salat DH, Hersch SM. A tale of two factors: what determines the rate of progression in Huntington's disease? A longitudinal MRI study. Mov Disord. 2011 Aug 1;26(9):1691-7. doi: 10.1002/mds.23762. Epub 2011 May 24."}, {'pmid': '20460152', 'type': 'BACKGROUND', 'citation': "Kim J, Amante DJ, Moody JP, Edgerly CK, Bordiuk OL, Smith K, Matson SA, Matson WR, Scherzer CR, Rosas HD, Hersch SM, Ferrante RJ. Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):673-81. doi: 10.1016/j.bbadis.2010.05.001. Epub 2010 May 9."}, {'pmid': '19850138', 'type': 'BACKGROUND', 'citation': 'Rosas HD, Lee SY, Bender AC, Zaleta AK, Vangel M, Yu P, Fischl B, Pappu V, Onorato C, Cha JH, Salat DH, Hersch SM. Altered white matter microstructure in the corpus callosum in Huntington\'s disease: implications for cortical "disconnection". Neuroimage. 2010 Feb 15;49(4):2995-3004. doi: 10.1016/j.neuroimage.2009.10.015. Epub 2009 Oct 19.'}, {'pmid': '19076442', 'type': 'BACKGROUND', 'citation': "Rosas HD, Salat DH, Lee SY, Zaleta AK, Hevelone N, Hersch SM. Complexity and heterogeneity: what drives the ever-changing brain in Huntington's disease? Ann N Y Acad Sci. 2008 Dec;1147:196-205. doi: 10.1196/annals.1427.034."}, {'pmid': '18394565', 'type': 'BACKGROUND', 'citation': "Hersch SM, Rosas HD. Neuroprotection for Huntington's disease: ready, set, slow. Neurotherapeutics. 2008 Apr;5(2):226-36. doi: 10.1016/j.nurt.2008.01.003."}, {'pmid': '18337273', 'type': 'BACKGROUND', 'citation': "Rosas HD, Salat DH, Lee SY, Zaleta AK, Pappu V, Fischl B, Greve D, Hevelone N, Hersch SM. Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity. Brain. 2008 Apr;131(Pt 4):1057-68. doi: 10.1093/brain/awn025. Epub 2008 Mar 12."}, {'pmid': '16434666', 'type': 'BACKGROUND', 'citation': "Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology. 2006 Jan 24;66(2):250-2. doi: 10.1212/01.wnl.0000194318.74946.b6."}, {'pmid': '16755582', 'type': 'BACKGROUND', 'citation': "Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, Salat DH. Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures. Mov Disord. 2006 Sep;21(9):1317-25. doi: 10.1002/mds.20979."}, {'pmid': '16055197', 'type': 'BACKGROUND', 'citation': "Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005 Nov;108(2):193-207. doi: 10.1016/j.pharmthera.2005.04.008. Epub 2005 Aug 1."}, {'pmid': '16043692', 'type': 'BACKGROUND', 'citation': "Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, Krainc D. Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11023-8. doi: 10.1073/pnas.0504921102. Epub 2005 Jul 25."}, {'pmid': '11889230', 'type': 'BACKGROUND', 'citation': "Rosas HD, Liu AK, Hersch S, Glessner M, Ferrante RJ, Salat DH, van der Kouwe A, Jenkins BG, Dale AM, Fischl B. Regional and progressive thinning of the cortical ribbon in Huntington's disease. Neurology. 2002 Mar 12;58(5):695-701. doi: 10.1212/wnl.58.5.695."}, {'pmid': '19811052', 'type': 'BACKGROUND', 'citation': "Hersch SM, Rosas HD. Neuroprotective therapy for Huntington's disease: new prospects and challenges. Expert Rev Neurother. 2001 Sep;1(1):111-8. doi: 10.1586/14737175.1.1.111."}, {'pmid': '18032664', 'type': 'BACKGROUND', 'citation': "Stack EC, Dedeoglu A, Smith KM, Cormier K, Kubilus JK, Bogdanov M, Matson WR, Yang L, Jenkins BG, Luthi-Carter R, Kowall NW, Hersch SM, Beal MF, Ferrante RJ. Neuroprotective effects of synaptic modulation in Huntington's disease R6/2 mice. J Neurosci. 2007 Nov 21;27(47):12908-15. doi: 10.1523/JNEUROSCI.4318-07.2007."}, {'pmid': '12787055', 'type': 'BACKGROUND', 'citation': "Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67. doi: 10.1046/j.1471-4159.2003.01706.x."}]}, 'descriptionModule': {'briefSummary': "The purpose of this clinical trial is to extend the Pre-Crest study (Protocol # (NCT00592995) to further assess the long-term safety and tolerability of up to 30 grams daily creatine in individuals at-risk for Huntington's Disease (HD) and to assess whether biomarkers responsive to creatine in symptomatic individuals are informative in premanifest individuals over a longer duration.", 'detailedDescription': "Extensive evidence exists that neurodegeneration begins many years before HD can be diagnosed clinically. Therefore, it is most desirable to begin a neuroprotective therapy before or during this premanifest period with the aim of delaying onset, as well as slowing functional decline. Cellular energy depletion is present early in HD and can be ameliorated by creatine, which helps regenerate cellular ATP. Preclinical evidence for creatine's potential neuroprotective effects in animal models of HD has been well-documented. Before the clinical efficacy of creatine can be tested in premanifest HD, its long-term safety and tolerability must be assessed in these individuals and its ability to favorably modify biomarkers of HD should also be confirmed. This extension trial will continue to follow eligible individuals who completed the PreCREST study on open-label creatine (up to 30 grams daily) for long term safety and tolerability. Additional biological and imaging biomarkers of disease progression and potential response to treatment will also be assessed."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '26 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Individuals who have completed the Pre-CREST Study.\n* Individuals capable of providing independent informed consent and complying with trial procedures.\n\nExclusion Criteria:\n\n-Clinical evidence of unstable medical or psychiatric illness in the investigator's judgment.\n\nAdditional eligibility criteria apply."}, 'identificationModule': {'nctId': 'NCT01411150', 'acronym': 'Pre-CREST-X', 'briefTitle': "Premanifest Huntington's Disease: Creatine Safety & Tolerability Extension Study", 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'officialTitle': "Premanifest Huntington's Disease: Creatine Safety & Tolerability Extension Study", 'orgStudyIdInfo': {'id': '2009P000642'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Creatine', 'interventionNames': ['Drug: Creatine Monohydrate']}], 'interventions': [{'name': 'Creatine Monohydrate', 'type': 'DRUG', 'description': 'Up to 30 grams daily creatine monohydrate', 'armGroupLabels': ['Creatine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02129', 'city': 'Charlestown', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.37787, 'lon': -71.062}}], 'overallOfficials': [{'name': 'Diana Rosas, MD, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Neurology', 'investigatorFullName': 'Steven M. Hersch', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}