Ignite Creation Date:
2025-12-24 @ 11:29 PM
Ignite Modification Date:
2025-12-30 @ 9:31 PM
Study NCT ID:
NCT03814356
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-29
First Post:
2019-01-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D004194', 'term': 'Disease'}, {'id': 'D003128', 'term': 'Coma'}, {'id': 'D003244', 'term': 'Consciousness Disorders'}, {'id': 'D020925', 'term': 'Hypoxia-Ischemia, Brain'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D014474', 'term': 'Unconsciousness'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D002545', 'term': 'Brain Ischemia'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D002534', 'term': 'Hypoxia, Brain'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D000860', 'term': 'Hypoxia'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008774', 'term': 'Methylphenidate'}, {'id': 'C041626', 'term': '5,10-dihydro-5-methylphenazine'}], 'ancestors': [{'id': 'D010648', 'term': 'Phenylacetates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010880', 'term': 'Piperidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'bedlow@mgh.harvard.edu', 'phone': '617-724-6352', 'title': 'Brian L. Edlow, M.D.', 'organization': 'Massachusetts General Hospital'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '4 days', 'eventGroups': [{'id': 'EG000', 'title': '0.5 mg/kg IV MPH', 'description': '9 patients received 0.5 mg/kg IV MPH.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 0, 'seriousNumAtRisk': 9, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': '1.0 mg/kg IV MPH', 'description': '9 patients received 1.0 mg/kg IV MPH.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 2, 'seriousNumAtRisk': 9, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': '2.0 mg/kg IV MPH', 'description': '6 patients received 0.5 mg/kg IV MPH.', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Paroxysmal Sympathetic Hyperactivity', 'notes': 'assessed at bedside in ICU', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED'}, {'term': 'Insomnia', 'notes': 'assessed at bedside in ICU', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED'}, {'term': 'Emesis', 'notes': 'assessed at bedside in ICU', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED'}, {'term': 'Transaminitis (increased ALT/AST)', 'notes': 'assessed via lab analysis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Adverse Events at Each Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'IV MPH', 'description': 'All patients received IV Methylphenidate (MPH). Patients received escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitated dose de-escalation or a serious adverse event (SAE) necessitated that the patient stop participation in the study.'}], 'classes': [{'title': '0.5 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': '1.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': '2.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '4 Days', 'description': 'Adverse Events\n\nAn AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). In the STIMPACT Trial an AE may include, but is not limited to:\n\n* Sustained hypertension = SBP \\> 200 mmHg or DBP \\> 120 mmHg for \\> 30 min, refractory to medical therapy, or\n* Sustained tachycardia = HR \\> 120 bpm for \\> 30 min, refractory to medical therapy, or\n* Sustained intracranial hypertension = ICP \\> 25 mmHg for \\> 5 min, refractory to medical therapy\n\nSerious Adverse Events\n\nAn AE or suspected adverse reaction is considered "serious" if, in the view of the investigator or the Independent Medical Monitor, it results in any of the following outcomes:\n\n* Death not related to withdrawal of life-sustaining therapy\n* A life-threatening event\n* Prolongation of existing hospitalization\n* Significant incapacity or substantial disruption of the ability to conduct normal life function', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': '9 participants received the 0.5 mg/kg IV MPH dose and and the 1.0 mg/kg IV MPH dose. 6 participants received the 2.0 mg/kg IV MPH dose.'}, {'type': 'SECONDARY', 'title': 'Time to Maximal Serum Concentration of IV Methylphenidate (MPH)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'IV MPH', 'description': '9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.'}], 'classes': [{'title': '0.5 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.12', 'groupId': 'OG000', 'lowerLimit': '0.08', 'upperLimit': '0.13'}]}]}, {'title': '1.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.15', 'groupId': 'OG000', 'lowerLimit': '0.07', 'upperLimit': '0.18'}]}]}, {'title': '2.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.23', 'groupId': 'OG000', 'lowerLimit': '0.2', 'upperLimit': '0.3'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '4 Days', 'description': 'The median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses was measured.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'We measured the median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses of IV MPH.'}, {'type': 'SECONDARY', 'title': 'Serum Half-life of IV Methylphenidate (MPH)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'IV MPH', 'description': '9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.'}], 'classes': [{'title': '0.5 mg/kg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '5.07', 'spread': '2.55', 'groupId': 'OG000'}]}]}, {'title': '1.0 mg/kg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '4.39', 'spread': '1.92', 'groupId': 'OG000'}]}]}, {'title': '2.0 mg/kg', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '5.01', 'spread': '1.80', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 Days', 'description': 'The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.', 'unitOfMeasure': 'hours', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.'}, {'type': 'SECONDARY', 'title': 'Cerebral Cortical Connectivity as Measured by fMRI', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'IV MPH', 'description': '9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '4 Days', 'description': 'We performed a change-point analysis of time-series resting-state fMRI data to determine if individual participants responded to the 2.0 mg/kg dose of IV MPH. Specifically, we measured resting-state fMRI connectivity between the brainstem ventral tegmental area and the default mode network after the bolus of IV MPH as compared to before the bolus of IV MPH. The bolus of IV MPH was administered in the MRI scanner while the patient was undergoing a 40-minute resting-state fMRI (10 minutes of data acquisition pre-bolus, 30 minutes of data acquisition post-bolus). The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in connectivity after the bolus of IV MPH). Connectivity was measured via Pearson correlations using the software package CONN.', 'unitOfMeasure': 'number of responders', 'reportingStatus': 'POSTED', 'populationDescription': 'Functional MRI data were obtained in two study participants.'}, {'type': 'SECONDARY', 'title': 'Cerebral Cortical Connectivity as Measured by EEG', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'IV MPH', 'description': '9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.'}], 'classes': [{'title': '0.5 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': '1.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': '2.0 mg/kg IV MPH', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '4 Days', 'description': 'We performed a change-point analysis of time-series resting-state EEG data to determine if individual participants responded to each dose of IV MPH. Specifically, we measured resting-state EEG background rhythm, using the alpha/delta ratio as a quantitative biomarker of overall brain function (i.e., alpha/delta ratio was measured for all EEG leads in a clinical 19-electrode montage). In a continuous time-series analysis of resting EEG data acquired 1 hour before and 1 hour after each IV MPH bolus, we tested for a "change-point" in the alpha/delta ratio, which represents a statistically significant increase in alpha/delta ratio. The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in alpha/delta after the bolus of IV MPH). EEG analyses were performed using MATLAB software.', 'unitOfMeasure': 'number of responders', 'reportingStatus': 'POSTED', 'populationDescription': 'EEG data were obtained in all nine study participants at the 0.5 mg/kg dose and 1.0 mg/kg dose, and in 6 participants at the 2.0 mg/kg dose.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'IV MPH', 'description': 'All patients will receive IV Methylphenidate (MPH). Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study.\n\nMethylphenidate: IV MPH'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': '10 patients were enrolled with informed consent provided by surrogate decision-makers, but one patient was withdrawn from the study by surrogate decision-makers prior to any study procedures were performed.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'IV MPH', 'description': '9 patients with severe traumatic brain injury (TBI), age range 25-77, all male.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '49.3', 'spread': '21.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'adults with severe TBI'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-12-16', 'size': 368939, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-09-05T16:13', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2020-08-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-15', 'studyFirstSubmitDate': '2019-01-15', 'resultsFirstSubmitDate': '2025-08-12', 'studyFirstSubmitQcDate': '2019-01-18', 'lastUpdatePostDateStruct': {'date': '2025-10-29', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2025-10-15', 'studyFirstPostDateStruct': {'date': '2019-01-24', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-10-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2024-04-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Adverse Events at Each Dose', 'timeFrame': '4 Days', 'description': 'Adverse Events\n\nAn AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). In the STIMPACT Trial an AE may include, but is not limited to:\n\n* Sustained hypertension = SBP \\> 200 mmHg or DBP \\> 120 mmHg for \\> 30 min, refractory to medical therapy, or\n* Sustained tachycardia = HR \\> 120 bpm for \\> 30 min, refractory to medical therapy, or\n* Sustained intracranial hypertension = ICP \\> 25 mmHg for \\> 5 min, refractory to medical therapy\n\nSerious Adverse Events\n\nAn AE or suspected adverse reaction is considered "serious" if, in the view of the investigator or the Independent Medical Monitor, it results in any of the following outcomes:\n\n* Death not related to withdrawal of life-sustaining therapy\n* A life-threatening event\n* Prolongation of existing hospitalization\n* Significant incapacity or substantial disruption of the ability to conduct normal life function'}], 'secondaryOutcomes': [{'measure': 'Time to Maximal Serum Concentration of IV Methylphenidate (MPH)', 'timeFrame': '4 Days', 'description': 'The median (range) time (hours) to maximum concentrations at 0.5, 1.0, and 2.0 mg/kg doses was measured.'}, {'measure': 'Serum Half-life of IV Methylphenidate (MPH)', 'timeFrame': '4 Days', 'description': 'The mean (SD) serum half-lives (hours) at 0.5, 1.0, and 2.0 mg/kg doses was assessed.'}, {'measure': 'Cerebral Cortical Connectivity as Measured by fMRI', 'timeFrame': '4 Days', 'description': 'We performed a change-point analysis of time-series resting-state fMRI data to determine if individual participants responded to the 2.0 mg/kg dose of IV MPH. Specifically, we measured resting-state fMRI connectivity between the brainstem ventral tegmental area and the default mode network after the bolus of IV MPH as compared to before the bolus of IV MPH. The bolus of IV MPH was administered in the MRI scanner while the patient was undergoing a 40-minute resting-state fMRI (10 minutes of data acquisition pre-bolus, 30 minutes of data acquisition post-bolus). The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in connectivity after the bolus of IV MPH). Connectivity was measured via Pearson correlations using the software package CONN.'}, {'measure': 'Cerebral Cortical Connectivity as Measured by EEG', 'timeFrame': '4 Days', 'description': 'We performed a change-point analysis of time-series resting-state EEG data to determine if individual participants responded to each dose of IV MPH. Specifically, we measured resting-state EEG background rhythm, using the alpha/delta ratio as a quantitative biomarker of overall brain function (i.e., alpha/delta ratio was measured for all EEG leads in a clinical 19-electrode montage). In a continuous time-series analysis of resting EEG data acquired 1 hour before and 1 hour after each IV MPH bolus, we tested for a "change-point" in the alpha/delta ratio, which represents a statistically significant increase in alpha/delta ratio. The goal of the analysis was to determine if each patient responded to IV MPH, as defined by a positive change point (i.e., increase in alpha/delta after the bolus of IV MPH). EEG analyses were performed using MATLAB software.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Brain Injury Traumatic Severe (Diagnosis)', 'Coma', 'Consciousness, Level Altered', 'Anoxic Brain Injury']}, 'referencesModule': {'references': [{'pmid': '32794142', 'type': 'BACKGROUND', 'citation': 'Edlow BL, Barra ME, Zhou DW, Foulkes AS, Snider SB, Threlkeld ZD, Chakravarty S, Kirsch JE, Chan ST, Meisler SL, Bleck TP, Fins JJ, Giacino JT, Hochberg LR, Solt K, Brown EN, Bodien YG. Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit. Neurocrit Care. 2020 Oct;33(2):364-375. doi: 10.1007/s12028-020-01062-7. Epub 2020 Aug 13.'}], 'seeAlsoLinks': [{'url': 'https://www.comarecoverylab.org/', 'label': 'Homepage of the Laboratory for NeuroImaging of Coma and Consciousness'}]}, 'descriptionModule': {'briefSummary': 'Phase 1 of the STIMPACT trial is an open label,dose-escalation,safety study of intravenous (IV) methylphenidate (MPH) therapy in patients with disorders of consciousness (DoC) caused by severe brain injuries.', 'detailedDescription': 'To be classified as having a DoC, a patient must be in a coma, vegetative state (VS), or minimally conscious state (MCS), as determined by behavioral assessment using the Coma Recovery Scale-Revised (CRS-R). Patients with DoC admitted to the intensive care unit (ICU) will be eligible for the study. A total of 10 patients with DoC will be enrolled in the Phase 1 study. Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study. Pharmacokinetics will be evaluated in selected patients with indwelling venous catheters or arterial catheters via serial serum measurements of MPH at each dose. The pharmacodynamic properties of IV MPH at each dose will be assessed by comparison of pre-versus post-dose EEG-based measures. The pharmacodynamic properties of the maximum tolerated dose will also be assessed by comparison of pre-versus post-dose resting state functional MRI (rs-fMRI) connectivity measures. Finally, we will test the association between structural connectivity of the ventral tegmental area (VTA), a dopaminergic brainstem nucleus that is believed to mediate MPH activation of the cerebral cortex, and EEG and rs-fMRI pharmacodynamic measures.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age ≥ 18 years\n2. Severe, acute traumatic brain injury\n3. Diagnosis of Coma, Vegetative State, or Minimally Conscious State\n\nExclusion Criteria:\n\n1. Penetrating brain injury caused by a metallic missile/object (e.g. bullet)\n2. Body metal contraindicating MRI\n3. Prisoner or ward of the state\n4. Neurological\n\n 1. Bilateral dilated unresponsive pupils\n 2. Intracranial hypertension (Intracranial Pressure \\[ICP\\] \\> 25 mmHg for \\> 5 min within past 24 hours with head-of-bed at standard clinical angle of 30-45 degrees)\n 3. Intracranial bolt\n 4. Status epilepticus or concern for post-ictal state\n5. Cardiovascular\n\n 1. Poorly controlled hypertension (SBP \\> 200 mmHg of DBP \\> 120mmHg for 30 minutes, despite anti-hypertensive therapy, within the past 24 hours)\n 2. Coronary artery disease\n 3. ST elevation myocardial infarction\n 4. Acute coronary syndrome\n 5. Hemodynamically significant dysrhythmia\n 6. Congestive heart failure\n 7. Cardiomyopathy (including Takotsubo cardiomyopathy)\n 8. Other severe structural cardiac abnormalities\n6. Renal\n\n a. Renal failure requiring renal replacement therapy (e.g. CVVH or HD)\n7. Endocrine\n\n a. History of or clinical suspicion for thyrotoxicosis\n8. Reproductive\n\n a. Pregnancy\n9. Ophthalmologic\n\n a. History of glaucoma\n10. Pharmacologic\n\n a. Monoamine oxidase inhibitor therapy within past 14 days\n11. Other\n\n 1. Any condition or finding that in the judgment of the PI or treating clinical team significantly increases the risk or significantly decreases the likelihood of a response to IV MPH'}, 'identificationModule': {'nctId': 'NCT03814356', 'acronym': 'STIMPACT', 'briefTitle': 'Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'officialTitle': 'Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness - A Phase 1 Study', 'orgStudyIdInfo': {'id': '140675'}, 'secondaryIdInfos': [{'id': 'DP2HD101400', 'link': 'https://reporter.nih.gov/quickSearch/DP2HD101400', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'IV MPH', 'description': 'All patients will receive IV Methylphenidate (MPH). Patients will receive escalating daily doses of IV MPH starting at 0.5 mg/kg, increasing stepwise to 1.0mg/kg and 2.0 mg/kg unless an adverse event (AE) necessitates dose de-escalation or a serious adverse event (SAE) necessitates that the patient stop participation in the study.', 'interventionNames': ['Drug: Methylphenidate']}], 'interventions': [{'name': 'Methylphenidate', 'type': 'DRUG', 'otherNames': ['MPH'], 'description': 'IV MPH', 'armGroupLabels': ['IV MPH']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Brian L Edlow, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Director, Laboratory for NeuroImaging of Coma and Consciousness (NICC)', 'investigatorFullName': 'Brian L. Edlow, M.D.', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}