Ignite Creation Date:
2025-12-24 @ 7:25 PM
Ignite Modification Date:
2025-12-25 @ 5:06 PM
Study NCT ID:
NCT01182103
Status:
COMPLETED
Last Update Posted:
2014-08-15
First Post:
2010-08-11
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Epigenetic Regulation of BDNF in Major Depression
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003865', 'term': 'Depressive Disorder, Major'}], 'ancestors': [{'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'a540520@adm.cgmh.org.tw', 'phone': '886-7-7317123', 'title': 'Tiao-Lai Huang', 'phoneExt': '8753', 'organization': 'Kaohsiung Chang Gung Memorial Hospital'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Limited funding prevented all samples from receiving all analyses.'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Major Depressive Patients', 'otherNumAtRisk': 48, 'otherNumAffected': 0, 'seriousNumAtRisk': 48, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Healthy Subjects', 'otherNumAtRisk': 62, 'otherNumAffected': 0, 'seriousNumAtRisk': 62, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Major Depressive Patients'}, {'id': 'OG001', 'title': 'Healthy Subjects'}], 'classes': [{'title': 'CpG site 24', 'categories': [{'measurements': [{'value': '92', 'spread': '5.0', 'groupId': 'OG000'}, {'value': '92', 'spread': '3.0', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 57', 'categories': [{'measurements': [{'value': '75', 'spread': '5.4', 'groupId': 'OG000'}, {'value': '75', 'spread': '4.8', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 80', 'categories': [{'measurements': [{'value': '65', 'spread': '7.6', 'groupId': 'OG000'}, {'value': '63', 'spread': '6.2', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 134', 'categories': [{'measurements': [{'value': '87', 'spread': '4.2', 'groupId': 'OG000'}, {'value': '86', 'spread': '3.8', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 140', 'categories': [{'measurements': [{'value': '49', 'spread': '23.2', 'groupId': 'OG000'}, {'value': '41', 'spread': '24.7', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 177', 'categories': [{'measurements': [{'value': '93', 'spread': '3.9', 'groupId': 'OG000'}, {'value': '94', 'spread': '2.3', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 203', 'categories': [{'measurements': [{'value': '88', 'spread': '5.2', 'groupId': 'OG000'}, {'value': '90', 'spread': '2.9', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 217', 'categories': [{'measurements': [{'value': '61', 'spread': '8.0', 'groupId': 'OG000'}, {'value': '51', 'spread': '11.4', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 324', 'categories': [{'measurements': [{'value': '95', 'spread': '4.8', 'groupId': 'OG000'}, {'value': '95', 'spread': '2.4', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 327', 'categories': [{'measurements': [{'value': '88', 'spread': '4.7', 'groupId': 'OG000'}, {'value': '90', 'spread': '2.5', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 345', 'categories': [{'measurements': [{'value': '97', 'spread': '5.0', 'groupId': 'OG000'}, {'value': '98', 'spread': '3.0', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 348', 'categories': [{'measurements': [{'value': '90', 'spread': '6.0', 'groupId': 'OG000'}, {'value': '91', 'spread': '4.1', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 362', 'categories': [{'measurements': [{'value': '89', 'spread': '4.4', 'groupId': 'OG000'}, {'value': '91', 'spread': '2.0', 'groupId': 'OG001'}]}]}, {'title': 'CpG site 391', 'categories': [{'measurements': [{'value': '84', 'spread': '4.8', 'groupId': 'OG000'}, {'value': '85', 'spread': '3.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001'], 'ciPctValue': '95', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '2 years', 'description': 'averaged percentage of methylation at each CpG site listed', 'unitOfMeasure': 'percent', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 39 out of the 48 MDD patients provided enough blood sample for this analysis.'}, {'type': 'PRIMARY', 'title': 'Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}, {'value': '37', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Healthy Subjects'}, {'id': 'OG001', 'title': 'Major Depressive Patients Before Treatment'}, {'id': 'OG002', 'title': 'Major Depressive Patients After Treatment'}], 'classes': [{'title': 'BDNF promotor I acetyl-H3', 'categories': [{'measurements': [{'value': '3.5610', 'spread': '2.79865', 'groupId': 'OG000'}, {'value': '.3124', 'spread': '.53231', 'groupId': 'OG001'}, {'value': '.4321', 'spread': '.32039', 'groupId': 'OG002'}]}]}, {'title': 'BDNF promotor I acetyl-H4', 'categories': [{'measurements': [{'value': '2.6346', 'spread': '2.66175', 'groupId': 'OG000'}, {'value': '.3784', 'spread': '.54543', 'groupId': 'OG001'}, {'value': '.4659', 'spread': '.62056', 'groupId': 'OG002'}]}]}, {'title': 'BDNF promotor IV acetyl-H3', 'categories': [{'measurements': [{'value': '1.6356', 'spread': '2.33692', 'groupId': 'OG000'}, {'value': '.4059', 'spread': '.43157', 'groupId': 'OG001'}, {'value': '.4303', 'spread': '.70365', 'groupId': 'OG002'}]}]}, {'title': 'BDNF promotor IV acetyl-H4', 'categories': [{'measurements': [{'value': '2.2795', 'spread': '2.66175', 'groupId': 'OG000'}, {'value': '.4676', 'spread': '.54543', 'groupId': 'OG001'}, {'value': '.4988', 'spread': '.62056', 'groupId': 'OG002'}]}]}, {'title': 'BDNF promotor X acetyl-H3', 'categories': [{'measurements': [{'value': '3.8960', 'spread': '1.94450', 'groupId': 'OG000'}, {'value': '.2564', 'spread': '.36703', 'groupId': 'OG001'}, {'value': '.3640', 'spread': '.34533', 'groupId': 'OG002'}]}]}, {'title': 'BDNF promotor X acetyl-H4', 'categories': [{'measurements': [{'value': '1.7433', 'spread': '2.66175', 'groupId': 'OG000'}, {'value': '.2105', 'spread': '.30502', 'groupId': 'OG001'}, {'value': '.2540', 'spread': '.53050', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '2 years', 'description': "Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in:\n\nHuebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369.", 'unitOfMeasure': 'relative quantification', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '48', 'groupId': 'OG001'}, {'value': '48', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Healthy Subjects'}, {'id': 'OG001', 'title': 'Major Depressive Patients Before Treatment'}, {'id': 'OG002', 'title': 'Major Depressive Patients After Treatment'}], 'classes': [{'categories': [{'measurements': [{'value': '7.9386', 'spread': '3.24400', 'groupId': 'OG000'}, {'value': '5.6014', 'spread': '4.46981', 'groupId': 'OG001'}, {'value': '6.2803', 'spread': '5.58535', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.05', 'groupIds': ['OG000', 'OG001', 'OG002'], 'ciPctValue': '95', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '2 years', 'description': 'Serum BDNF levels were measured. MDD patients received antidepressant treatment, a standard biological management. Nothing novel (such as experimental drugs or management) is introduced in the treatment, so the research design is observational (of standard treatment).\n\nThe choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Major Depressive Patients'}, {'id': 'FG001', 'title': 'Healthy Subjects'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '48'}, {'groupId': 'FG001', 'numSubjects': '62'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '48'}, {'groupId': 'FG001', 'numSubjects': '62'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'From August 1st, 2000 to July 31st, 2012, major depressive disorder patients were recruited from Kaohsiung Chang Gung Memorial Hospital, a tertiary medical center.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '48', 'groupId': 'BG000'}, {'value': '62', 'groupId': 'BG001'}, {'value': '110', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Major Depressive Patients'}, {'id': 'BG001', 'title': 'Healthy Subjects'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '48', 'groupId': 'BG000'}, {'value': '62', 'groupId': 'BG001'}, {'value': '110', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '42.44', 'spread': '12.09', 'groupId': 'BG000'}, {'value': '30.18', 'spread': '5.6', 'groupId': 'BG001'}, {'value': '35.53', 'spread': '10.81', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '38', 'groupId': 'BG001'}, {'value': '70', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '40', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Taiwan', 'categories': [{'measurements': [{'value': '48', 'groupId': 'BG000'}, {'value': '62', 'groupId': 'BG001'}, {'value': '110', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 110}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-07', 'completionDateStruct': {'date': '2013-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-07-24', 'studyFirstSubmitDate': '2010-08-11', 'resultsFirstSubmitDate': '2013-06-07', 'studyFirstSubmitQcDate': '2010-08-13', 'lastUpdatePostDateStruct': {'date': '2014-08-15', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2014-07-24', 'studyFirstPostDateStruct': {'date': '2010-08-16', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2014-08-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls', 'timeFrame': '2 years', 'description': 'averaged percentage of methylation at each CpG site listed'}, {'measure': 'Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls', 'timeFrame': '2 years', 'description': "Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in:\n\nHuebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369."}], 'secondaryOutcomes': [{'measure': 'BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls', 'timeFrame': '2 years', 'description': 'Serum BDNF levels were measured. MDD patients received antidepressant treatment, a standard biological management. Nothing novel (such as experimental drugs or management) is introduced in the treatment, so the research design is observational (of standard treatment).\n\nThe choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Major depression', 'BDNF', 'DNA methylation', 'Histone modification'], 'conditions': ['Major Depressive Disorder']}, 'descriptionModule': {'briefSummary': 'The investigators will (1) detect the associations between brain-derived neurotrophic factor (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive disorder (MDD) patients, (2) check the correlation between blood BDNF protein and RNA and BDNF rs6265 gene, and (3) discuss the possible mechanisms of epigenetic regulation of BDNF in Taiwanese major depressive patients.', 'detailedDescription': 'Brain-derived neurotrophic factor (BDNF) had been chosen as a candidate gene for a development of major depressive disorder (MDD). BDNF had been reported to have an important role on neuronal plasticity, axonal growth and connectivity, and participating in the local response to various types of neuronal stressors. BDNF also influences the differentiation of neurons.\n\nIn the past studies, the investigators had found that major depressive women had lower serum BDNF protein levels than healthy controls, and their BDNF levels became significantly increased after antidepressant treatments. In addition, some authors had found that reduced expression of BDNF was noted in postmortem brain of completed suicide subjects. Suicidal major depressive patients also had lower plasma BDNF levels than non-suicidal major depressive patients. These findings suggested that BDNF might play an important role in the suicidal behavior.\n\nHowever, in past studies, the results did not fully explain why major depressive patients with same genotypes had different clinical expression, including the severity of depression, with/without suicide, and the treatment response. Recently, some papers found that there were relationships between epigenetic regulation, including DNA methylation and histone modification, and psychopathology of major depression. Therefore, we try to investigate the relationships between epigenetic regulation of BDNF and major depression.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'This 2-year study will be conducted in our clinical setting. By a semi-structured interview for DSM-IV criteria, a total of 160 subjectes (80 healthy controls and 80 patients with major depression) will be recruited in this study. In the first year (recruiting 40 healthy controls and 40 patients with major depression), the data of BDNF DNA methylation in all subjects will be collected. In the second year (recruiting another 40 healthy controls and 40 patients with major depression), the data of BDNF histone modification in all subjects will be collected and the mechanism of epigenetic regulation of BDNF in major depression will be discussed.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nThe clinical screening and assessment in patients with major depression：\n\n1. 40 major depression will be recruited in psychiatric inpatients according to DSM-IV criteria by a semi-structured interview. The assessment will be done by two senior psychiatrists. The intra-rater and inter-rater reliability will be done before this project started.\n2. The patients had the ability to complete the written inform consent.\n3. The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.\n4. The 17-item Hamilton Depression Rating Scale (HAM-D) was used to assess severity of depression. The minimum baseline score of the 17-item HAM-D was 18.\n\nExclusion Criteria:\n\n1. The patients had systemic diseases, including metabolic, heart, and liver diseases。\n2. The patients had received any drugs before entering this protocol.\n3. The patients were heavy smokers or dependent on alcohol.\n4. The use of secondary generation anti-psychotic drugs and mood stabilizers.'}, 'identificationModule': {'nctId': 'NCT01182103', 'briefTitle': 'Epigenetic Regulation of BDNF in Major Depression', 'organization': {'class': 'OTHER', 'fullName': 'Chang Gung Memorial Hospital'}, 'officialTitle': 'Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression', 'orgStudyIdInfo': {'id': 'NSC99-2628-B-182-002-MY2'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Major depressive patients'}, {'label': 'Healthy subjects'}]}, 'contactsLocationsModule': {'locations': [{'zip': '833', 'city': 'Kaohsiung City', 'country': 'Taiwan', 'facility': 'Department of Psychiatry, Chang Gung Memorial Hospital', 'geoPoint': {'lat': 22.61626, 'lon': 120.31333}}], 'overallOfficials': [{'name': 'Tiao-Lai Huang, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Chang-Gung Memorial Hospital, Kaohsiung'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Chang Gung Memorial Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Head of Department of Psychiatry', 'investigatorFullName': 'Tiao-Lai Huang', 'investigatorAffiliation': 'Chang Gung Memorial Hospital'}}}}