Ignite Creation Date:
2025-12-24 @ 12:13 PM
Ignite Modification Date:
2025-12-27 @ 9:15 PM
Study NCT ID:
NCT03461861
Status:
COMPLETED
Last Update Posted:
2023-07-03
First Post:
2018-02-26
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2022-05-25', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}, {'id': 'D003704', 'term': 'Dementia'}], 'ancestors': [{'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'yangwang@mcw.edu', 'phone': '4149555473', 'title': 'Dr. Yang Wang', 'organization': 'Medical College of Wisconsin'}, 'certainAgreement': {'otherDetails': "There is an agreement between Dr. Li and AgeneBio since AgeneBio supplies AGB101 drug to Dr. Li's for conducting the trial. The only restriction on the PI is that the sponsor can review results communications prior to public release.", 'restrictionType': 'OTHER', 'piSponsorEmployee': True, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': '26 total patients were enrolled in the project, and 25 total patients were included in analysis. One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis.'}}, 'adverseEventsModule': {'timeFrame': 'From Baseline Visit Through 4 Week Follow Up Call (an average of 12 weeks)', 'eventGroups': [{'id': 'EG000', 'title': 'AGB101 220 mg', 'description': 'AEs judged related to intervention while on AGB101 220 mg', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 6, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'AEs judged related to intervention while on Placebo', 'otherNumAtRisk': 26, 'deathsNumAtRisk': 26, 'otherNumAffected': 3, 'seriousNumAtRisk': 26, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Sleepiness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Brain Zaps', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Visual Aura', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Cold Symptoms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Feeling Jittery', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Depressed Mood', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 26, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '3'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Functional Connectivity Strengths of Neural Networks', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'AGB101 220 mg', 'description': 'AGB101 220 mg/day capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo, given as a capsule, once daily for 2 weeks.\n\nPlacebo: Placebo, oral capsule given once-daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.233', 'spread': '0.132', 'groupId': 'OG000'}, {'value': '0.318', 'spread': '0.127', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.007567', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Median Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.083', 'ciLowerLimit': '-0.0886', 'ciUpperLimit': '-0.0774', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '0.0056', 'groupDescription': 'The null hypothesis (H0) of this superiority trials asserts that there is no true difference in functional connectivity between the interventions of placebo and AGB101, and the alternative hypothesis (H1) states that there is a difference between the interventions of placebo and AGB101. A type I error is the error of rejecting H0 when it is actually true.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': '2 weeks after treatment between AGB101 and Placebo', 'description': 'The seed-based functional connectivity strengths of the hippocampus network and the default mode network will be employed to measure the changes between AGB101 and Placebo perturbation. The functional connectivity strengths will be measured with the median of the Pearson cross-correlation coefficients over entire brain regions.', 'unitOfMeasure': 'Pearson coefficient', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'A total of 25 subjects who were treated with AGB 101 and Placebo (order-balanced), then conducted a paired t-test to detect the treatment effect vs placebo.'}, {'type': 'SECONDARY', 'title': 'Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}, {'value': '25', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'AGB101 220 mg', 'description': 'AGB101 220 mg/day capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo, given as a capsule, once daily for 2 weeks.\n\nPlacebo: Placebo, oral capsule given once-daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '108', 'spread': '17', 'groupId': 'OG000'}, {'value': '105', 'spread': '16', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.900593', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '3.12', 'ciLowerLimit': '1.72', 'ciUpperLimit': '4.52', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '1.40', 'groupDescription': 'The null hypothesis (H0) of this trial asserts that there is no true difference in AVLT between the interventions of placebo and AGB101, and the alternative hypothesis (H1) states that there is a difference between the interventions of placebo and AGB101. A type I error is the error of rejecting H0 when it is actually true.', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Placebo vs AGB101 2 weeks after treatment paired t-test', 'description': 'Rey Auditory Verbal Learning Test (AVLT), delayed recall Scaled integer will be employed to measure the episodic memory changes before and after AGB101 treatment. The AVLT score will be recorded as a standard score. The theoretical range: min 50, max 155, the higher the better. The higher the number is, the better the memory. It is an integer number.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Measure RAVLT Delayed recall standard score memory test'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'AGB101 220 mg, Then Placebo', 'description': 'AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.\n\nPlacebo: Placebo, oral capsule given once-daily.'}, {'id': 'FG001', 'title': 'Placebo, Then AGB101 220 mg', 'description': 'Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.\n\nPlacebo: Placebo, oral capsule given once-daily.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '13'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '25', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'AGB101 220 mg, Then Placebo', 'description': 'AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.\n\nPlacebo: Placebo, oral capsule given once-daily.'}, {'id': 'BG001', 'title': 'Placebo, Then AGB101 220 mg', 'description': 'Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.\n\nAGB101 220 mg: AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.\n\nPlacebo: Placebo, oral capsule given once-daily.'}, {'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': '5', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '66', 'spread': '4', 'groupId': 'BG000'}, {'value': '67', 'spread': '5', 'groupId': 'BG001'}, {'value': '66.2', 'spread': '4.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '25', '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', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'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': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '25', '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', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '13', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}, {'title': 'Apolipoprotein E (APOE) Status', 'classes': [{'categories': [{'title': 'APOE e4 Carrier', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'APOE e4 Non-Carrier', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}], 'populationDescription': 'One enrolled subject did not have detectable LEV in their blood sample and was discarded in analysis'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-04-01', 'size': 632205, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2022-04-27T17:38', 'hasProtocol': True}, {'date': '2019-04-01', 'size': 1176337, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_002.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2022-12-07T15:52', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'This is a randomized, double-blind, placebo-controlled crossover study in which a low dose of AGB101 (220mg QD) or placebo will be administered to 50 healthy 55-75-year-old subjects, with the order of treatments counterbalanced in a within-subject crossover design.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-04-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-06', 'completionDateStruct': {'date': '2021-03-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-06-30', 'studyFirstSubmitDate': '2018-02-26', 'resultsFirstSubmitDate': '2022-04-28', 'studyFirstSubmitQcDate': '2018-03-05', 'lastUpdatePostDateStruct': {'date': '2023-07-03', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-06-30', 'studyFirstPostDateStruct': {'date': '2018-03-12', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2023-07-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-03-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Functional Connectivity Strengths of Neural Networks', 'timeFrame': '2 weeks after treatment between AGB101 and Placebo', 'description': 'The seed-based functional connectivity strengths of the hippocampus network and the default mode network will be employed to measure the changes between AGB101 and Placebo perturbation. The functional connectivity strengths will be measured with the median of the Pearson cross-correlation coefficients over entire brain regions.'}], 'secondaryOutcomes': [{'measure': 'Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better', 'timeFrame': 'Placebo vs AGB101 2 weeks after treatment paired t-test', 'description': 'Rey Auditory Verbal Learning Test (AVLT), delayed recall Scaled integer will be employed to measure the episodic memory changes before and after AGB101 treatment. The AVLT score will be recorded as a standard score. The theoretical range: min 50, max 155, the higher the better. The higher the number is, the better the memory. It is an integer number.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Healthy', 'Adult', 'Normal Memory', 'APOE 4', 'Brain', 'Magnetic Resonance Imaging', 'MRI', "Alzheimer's disease", 'Hippocampus', 'Genetic testing', 'Dementia', 'AGB101'], 'conditions': ['APOE 4']}, 'referencesModule': {'references': [{'pmid': '14688411', 'type': 'BACKGROUND', 'citation': "Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9. doi: 10.1073/pnas.2635903100. Epub 2003 Dec 19."}, {'pmid': '19357304', 'type': 'BACKGROUND', 'citation': 'Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE. Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14. doi: 10.1073/pnas.0811879106. Epub 2009 Apr 8.'}, {'pmid': '19833321', 'type': 'BACKGROUND', 'citation': 'Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, Mintun MA. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry. 2010 Mar 15;67(6):584-7. doi: 10.1016/j.biopsych.2009.08.024. Epub 2009 Oct 14.'}, {'pmid': '24905971', 'type': 'BACKGROUND', 'citation': 'Li W, Antuono PG, Xie C, Chen G, Jones JL, Ward BD, Singh SP, Franczak MB, Goveas JS, Li SJ. Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers. Cortex. 2014 Aug;57:167-76. doi: 10.1016/j.cortex.2014.04.006. Epub 2014 Apr 30.'}, {'pmid': '21159973', 'type': 'BACKGROUND', 'citation': "Sheline YI, Morris JC, Snyder AZ, Price JL, Yan Z, D'Angelo G, Liu C, Dixit S, Benzinger T, Fagan A, Goate A, Mintun MA. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. J Neurosci. 2010 Dec 15;30(50):17035-40. doi: 10.1523/JNEUROSCI.3987-10.2010."}, {'pmid': '20032967', 'type': 'BACKGROUND', 'citation': 'Koh MT, Haberman RP, Foti S, McCown TJ, Gallagher M. Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology. 2010 Mar;35(4):1016-25. doi: 10.1038/npp.2009.207. Epub 2009 Dec 23.'}, {'pmid': '22869752', 'type': 'BACKGROUND', 'citation': "Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):E2895-903. doi: 10.1073/pnas.1121081109. Epub 2012 Aug 6."}, {'pmid': '23416036', 'type': 'BACKGROUND', 'citation': "Devi L, Ohno M. Effects of levetiracetam, an antiepileptic drug, on memory impairments associated with aging and Alzheimer's disease in mice. Neurobiol Learn Mem. 2013 May;102:7-11. doi: 10.1016/j.nlm.2013.02.001. Epub 2013 Feb 13."}, {'pmid': '22578498', 'type': 'BACKGROUND', 'citation': 'Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron. 2012 May 10;74(3):467-74. doi: 10.1016/j.neuron.2012.03.023.'}, {'pmid': '23835471', 'type': 'BACKGROUND', 'citation': 'Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, Hegde M, Cornes SB, Henry ML, Nelson AB, Seeley WW, Geschwind MD, Gorno-Tempini ML, Shih T, Kirsch HE, Garcia PA, Miller BL, Mucke L. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 2013 Sep 1;70(9):1158-66. doi: 10.1001/jamaneurol.2013.136.'}, {'pmid': '17785178', 'type': 'BACKGROUND', 'citation': "Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007 Sep 6;55(5):697-711. doi: 10.1016/j.neuron.2007.07.025."}, {'pmid': '21423560', 'type': 'BACKGROUND', 'citation': 'Tuminello ER, Han SD. The apolipoprotein e antagonistic pleiotropy hypothesis: review and recommendations. Int J Alzheimers Dis. 2011 Feb 24;2011:726197. doi: 10.4061/2011/726197.'}, {'pmid': '15236399', 'type': 'BACKGROUND', 'citation': 'Dickerson BC, Salat DH, Bates JF, Atiya M, Killiany RJ, Greve DN, Dale AM, Stern CE, Blacker D, Albert MS, Sperling RA. Medial temporal lobe function and structure in mild cognitive impairment. Ann Neurol. 2004 Jul;56(1):27-35. doi: 10.1002/ana.20163.'}, {'pmid': '12068009', 'type': 'BACKGROUND', 'citation': "Mohajeri MH, Saini K, Schultz JG, Wollmer MA, Hock C, Nitsch RM. Passive immunization against beta-amyloid peptide protects central nervous system (CNS) neurons from increased vulnerability associated with an Alzheimer's disease-causing mutation. J Biol Chem. 2002 Sep 6;277(36):33012-7. doi: 10.1074/jbc.M203193200. Epub 2002 Jun 14."}, {'pmid': '20980585', 'type': 'BACKGROUND', 'citation': "Tampellini D, Capetillo-Zarate E, Dumont M, Huang Z, Yu F, Lin MT, Gouras GK. Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice. J Neurosci. 2010 Oct 27;30(43):14299-304. doi: 10.1523/JNEUROSCI.3383-10.2010."}]}, 'descriptionModule': {'briefSummary': 'The purpose of this project is to test the hypothesis that AGB101 low dose levetiracetam extended release formulation can reduce abnormal hyperfunctional activity in the hippocampus in normal, healthy adults. The investigators will compare the functional connectivity results after taking AGB101 or placebo.', 'detailedDescription': "In this study the investigators want to find out whether the use of a perturbation, such as AGB101 low dose of levetiracetam extended release formulation, in healthy adults can reduce abnormal hippocampal network activity. The investigators also want to study whether this low dose of LEV can improve memory function.\n\nGeneric levetiracetam is a type of drug called an anti-epileptic or anti-seizure medication. It is FDA approved worldwide for adults and children as young as one month with seizures. It is a generic drug used in long-term epilepsy treatment. It is relatively safe and has an acceptable side-effect profile.\n\nAGB101 has been developed as a novel extended release formulation of low dose levetiracetam (below clinically marketed doses for epilepsy) for slowing the progression of amnestic mild cognitive impairment.\n\nIt is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '55 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Fluent in English\n* At least eight (8) years of education\n* Geriatric Depression Scale (GDS) (62) score \\< 6\n* Hachinski Ischemic Score ≤ 4\n* Normal general cognitive function as well as 1) normal memory function, documented by MOCA score of 23 or greater, and a RBANS Delayed Memory Index score of 85 or greater.\n\nExclusion Criteria:\n\n* Neurological disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or a history of significant head trauma or known structural brain abnormalities\n* Major psychiatric disease or chronic unstable medical conditions\n* History of drug abuse\n* History of alcohol abuse (4 or greater drinks per day on average)\n* Unable to complete MRI scans (no Pacemaker/Defibrillator)\n* Known clinically significant abnormalities in B12 or thyroid function tests\n* End Stage Renal Disease (ESRD)\n* Hemodialysis (HD)"}, 'identificationModule': {'nctId': 'NCT03461861', 'briefTitle': "Network-Level Mechanisms for Preclinical Alzheimer's Disease Development", 'organization': {'class': 'OTHER', 'fullName': 'Medical College of Wisconsin'}, 'officialTitle': "Network-Level Mechanisms for Preclinical Alzheimer's Disease Development", 'orgStudyIdInfo': {'id': 'PRO00031146'}, 'secondaryIdInfos': [{'id': 'R21AG056882-01', 'link': 'https://reporter.nih.gov/quickSearch/R21AG056882-01', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'AGB101 220 mg, then Placebo', 'description': 'AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.', 'interventionNames': ['Drug: AGB101 220 mg', 'Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Placebo, then AGB101 220 mg', 'description': 'Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.', 'interventionNames': ['Drug: AGB101 220 mg', 'Other: Placebo']}], 'interventions': [{'name': 'AGB101 220 mg', 'type': 'DRUG', 'description': 'AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.', 'armGroupLabels': ['AGB101 220 mg, then Placebo', 'Placebo, then AGB101 220 mg']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Placebo, oral capsule given once-daily.', 'armGroupLabels': ['AGB101 220 mg, then Placebo', 'Placebo, then AGB101 220 mg']}]}, 'contactsLocationsModule': {'locations': [{'zip': '53226', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'Froedtert & The Medical College of Wisconsin', 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}], 'overallOfficials': [{'name': 'Yang Wang, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The Medical College of Wisconsin'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Medical College of Wisconsin', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute on Aging (NIA)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Yang Wang', 'investigatorAffiliation': 'Medical College of Wisconsin'}}}}