{"protocolSection":{"identificationModule":{"nctId":"NCT02208466","orgStudyIdInfo":{"id":"2014P001046"},"organization":{"fullName":"Spaulding Rehabilitation Hospital","class":"OTHER"},"briefTitle":"Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients","officialTitle":"Effects of Contralesional Repetitive Magnetic Stimulation Combined With Fluoxetine on Motor Recovery in Acute Stroke Patients"},"statusModule":{"statusVerifiedDate":"2021-02","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2014-09"},"primaryCompletionDateStruct":{"date":"2019-06-25","type":"ACTUAL"},"completionDateStruct":{"date":"2019-06-25","type":"ACTUAL"},"studyFirstSubmitDate":"2014-07-28","studyFirstSubmitQcDate":"2014-08-01","studyFirstPostDateStruct":{"date":"2014-08-05","type":"ESTIMATED"},"resultsFirstSubmitDate":"2020-11-25","resultsFirstSubmitQcDate":"2021-02-02","resultsFirstPostDateStruct":{"date":"2021-02-21","type":"ACTUAL"},"lastUpdateSubmitDate":"2021-02-02","lastUpdatePostDateStruct":{"date":"2021-02-21","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Felipe Fregni","investigatorTitle":"Principal Investigator","investigatorAffiliation":"Spaulding Rehabilitation Hospital"},"leadSponsor":{"name":"Spaulding Rehabilitation Hospital","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"In this study investigator's aim to assess the effect of a type of non-invasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) in conjunction with fluoxetine on motor recovery after stroke."},"conditionsModule":{"conditions":["Stroke","Motor Function"],"keywords":["repetitive transcranial magnetic stimulation","rTMS","TMS","fluoxetine"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":44,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Active rTMS/active fluoxetine","type":"EXPERIMENTAL","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.","interventionNames":["Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)","Drug: Fluoxetine"]},{"label":"Sham rTMS/active fluoxetine","type":"EXPERIMENTAL","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.","interventionNames":["Drug: Fluoxetine","Device: Sham repetitive transcranial magnetic stimulation (rTMS)"]},{"label":"Sham rTMS/placebo fluoxetine","type":"EXPERIMENTAL","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.","interventionNames":["Device: Sham repetitive transcranial magnetic stimulation (rTMS)","Drug: Placebo Fluoxetine"]}],"interventions":[{"type":"DEVICE","name":"Active Repetitive Transcranial Magnetic Stimulation (rTMS)","description":"Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.","armGroupLabels":["Active rTMS/active fluoxetine"],"otherNames":["magnetic stimulation, Magstim"]},{"type":"DRUG","name":"Fluoxetine","description":"Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.","armGroupLabels":["Active rTMS/active fluoxetine","Sham rTMS/active fluoxetine"],"otherNames":["Prozac, Sarafem, Ladose, Fontex"]},{"type":"DEVICE","name":"Sham repetitive transcranial magnetic stimulation (rTMS)","description":"Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.","armGroupLabels":["Sham rTMS/active fluoxetine","Sham rTMS/placebo fluoxetine"],"otherNames":["Magstim, magnetic stimulation"]},{"type":"DRUG","name":"Placebo Fluoxetine","description":"Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.","armGroupLabels":["Sham rTMS/placebo fluoxetine"],"otherNames":["Prozac, Sarafem, Ladose, Fontex"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Changes in Motor Function (Jebsen-Taylor Task)","description":"Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.\n\nCalculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).","timeFrame":"baseline and 90 days"},{"measure":"Changes in Fugl-Meyer Assessment (FMA) Scale","description":"The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).","timeFrame":"baseline and 90 days"}],"secondaryOutcomes":[{"measure":"Changes in Cortical Excitability Measures","description":"We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).","timeFrame":"Baseline and 90 days"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Ischemic infarction within the past 2 years post event that has caused hemiparesis or hemiplegia, as self-reported and/or confirmed by medical record.\n* Older than 18 years old.\n* Upper extremity weakness defined as a score of \\>11 and ≤56 on the arm motor Fugl-Mayer motor scale.\n* Minimal pre-stroke disability defined as a score of \\<3 in the Modified Rankin Scale.\n* Subjects need to be able to follow directions and participate in 2 hours of testing with short breaks.\n* Subjects need to be able to provide informed consent.\n\nExclusion Criteria:\n\n* Any substantial decrease in alertness, language reception, or attention that might interfere with understanding instruction for motor testing\n* Excessive pain in any joint of the paretic extremity (not applicable to severe stroke subjects), as self reported\n* Contraindications to single pulse TMS (will be used to measure cortical excitability) such as: history of seizures, unexplained loss of consciousness, any metal implants in the head, frequent or severe headaches or neck pain, any other electronic implanted medical devices such as pacemakers, defibrillators, or implant medication pump.\n* Patients who have taken fluoxetine in the past 5 weeks.\n* Patients taking any other SSRI at the time of enrollment or in the previous month.\n* Patients taking any other medication likely to have adverse interaction with SSRIs (all the medications the patient is taking will be carefully reviewed, as noted below in \"Monitoring of important drug interactions\").\n* Active depression on admission to SRH defined by a score of 24 or higher in the Hamilton Depression Rating Scale (HAM-D)\n* Concurrent medical condition likely to worsen patient's functional status in the next 6 months such as: cancer, terminal heart, kidney or liver disease, as self-reported and/or confirmed by medical record.\n* Pregnancy.","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Felipe Fregni, MD PhD MPH","affiliation":"Spaulding Rehabilitation Hospital","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Spaulding Rehabilitation Hospital","city":"Charlestown","state":"Massachusetts","zip":"02129","country":"United States","geoPoint":{"lat":42.37787,"lon":-71.062}}]},"referencesModule":{"references":[{"pmid":"31286828","type":"DERIVED","citation":"Bonin Pinto C, Morales-Quezada L, de Toledo Piza PV, Zeng D, Saleh Velez FG, Ferreira IS, Lucena PH, Duarte D, Lopes F, El-Hagrassy MM, Rizzo LV, Camargo EC, Lin DJ, Mazwi N, Wang QM, Black-Schaffer R, Fregni F. Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial. Neurorehabil Neural Repair. 2019 Aug;33(8):643-655. doi: 10.1177/1545968319860483. Epub 2019 Jul 9."}]}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"Please note that from the 44 subjects enrolled, only 27 started (were randomized) as 17 subjects screened out during confirmation of eligibility after signing the consent form (some of the criteria could only be checked after consent).","groups":[{"id":"FG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days."},{"id":"FG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered."},{"id":"FG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"9"},{"groupId":"FG001","numSubjects":"10"},{"groupId":"FG002","numSubjects":"8"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"9"},{"groupId":"FG001","numSubjects":"10"},{"groupId":"FG002","numSubjects":"8"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days."},{"id":"BG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered."},{"id":"BG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days."},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"9"},{"groupId":"BG001","value":"10"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"27"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"57.22","spread":"9.39"},{"groupId":"BG001","value":"50.5","spread":"16.57"},{"groupId":"BG002","value":"57.38","spread":"9.96"},{"groupId":"BG003","value":"55.03","spread":"11.97"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"2"},{"groupId":"BG003","value":"11"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"5"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"6"},{"groupId":"BG003","value":"16"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"3"},{"groupId":"BG003","value":"5"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"8"},{"groupId":"BG001","value":"9"},{"groupId":"BG002","value":"5"},{"groupId":"BG003","value":"22"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Changes in Motor Function (Jebsen-Taylor Task)","description":"Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.\n\nCalculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).","populationDescription":"Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"seconds","timeFrame":"baseline and 90 days","groups":[{"id":"OG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days."},{"id":"OG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered."},{"id":"OG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-214.33","lowerLimit":"-289.32","upperLimit":"-139.35"},{"groupId":"OG001","value":"-50.16","lowerLimit":"-110.56","upperLimit":"-10.24"},{"groupId":"OG002","value":"-117.98","lowerLimit":"-197.39","upperLimit":"-38.58"}]}]}]},{"type":"PRIMARY","title":"Changes in Fugl-Meyer Assessment (FMA) Scale","description":"The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).","populationDescription":"Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"units on a scale","timeFrame":"baseline and 90 days","groups":[{"id":"OG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days."},{"id":"OG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered."},{"id":"OG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"10.10","lowerLimit":"4.06","upperLimit":"16.14"},{"groupId":"OG001","value":"6.73","lowerLimit":"1.28","upperLimit":"12.17"},{"groupId":"OG002","value":"15.55","lowerLimit":"9.16","upperLimit":"21.95"}]}]}]},{"type":"SECONDARY","title":"Changes in Cortical Excitability Measures","description":"We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).","populationDescription":"Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"95% Confidence Interval","unitOfMeasure":"motor evoked potential (mV)","timeFrame":"Baseline and 90 days","groups":[{"id":"OG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days."},{"id":"OG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered."},{"id":"OG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"9"},{"groupId":"OG001","value":"10"},{"groupId":"OG002","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.05","lowerLimit":"-0.34","upperLimit":"0.08"},{"groupId":"OG001","value":"-0.12","lowerLimit":"-0.33","upperLimit":"0.43"},{"groupId":"OG002","value":"0.33","lowerLimit":"0.07","upperLimit":"1.16"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"3 months","description":"adverse effects were collected with a questionnaire for adverse effects","eventGroups":[{"id":"EG000","title":"Active rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nActive Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.","deathsNumAffected":0,"deathsNumAtRisk":9,"seriousNumAffected":0,"seriousNumAtRisk":9,"otherNumAffected":2,"otherNumAtRisk":9},{"id":"EG001","title":"Sham rTMS/Active Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.\n\nFluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.","deathsNumAffected":0,"deathsNumAtRisk":10,"seriousNumAffected":0,"seriousNumAtRisk":10,"otherNumAffected":0,"otherNumAtRisk":10},{"id":"EG002","title":"Sham rTMS/Placebo Fluoxetine","description":"Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.\n\nSham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.\n\nPlacebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.","deathsNumAffected":0,"deathsNumAtRisk":8,"seriousNumAffected":0,"seriousNumAtRisk":8,"otherNumAffected":3,"otherNumAtRisk":8}],"otherEvents":[{"term":"Headache","organSystem":"Nervous system disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":3,"numAffected":2,"numAtRisk":9},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":10},{"groupId":"EG002","numEvents":6,"numAffected":3,"numAtRisk":8}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Dr. Felipe Fregni","organization":"Spaulding Rehabilitation Hospital","email":"fregni.felipe@mgh.harvard.edu","phone":"6179526158"}}},"documentSection":{"largeDocumentModule":{"largeDocs":[{"typeAbbrev":"Prot_SAP","hasProtocol":true,"hasSap":true,"hasIcf":false,"label":"Study Protocol and Statistical Analysis Plan","date":"2017-08-10","uploadDate":"2020-11-25T14:06","filename":"Prot_SAP_000.pdf","size":448412}]}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D020521","term":"Stroke"}],"ancestors":[{"id":"D002561","term":"Cerebrovascular Disorders"},{"id":"D001927","term":"Brain Diseases"},{"id":"D002493","term":"Central Nervous System Diseases"},{"id":"D009422","term":"Nervous System Diseases"},{"id":"D014652","term":"Vascular Diseases"},{"id":"D002318","term":"Cardiovascular Diseases"}]},"interventionBrowseModule":{"meshes":[{"id":"D005473","term":"Fluoxetine"}],"ancestors":[{"id":"D011437","term":"Propylamines"},{"id":"D000588","term":"Amines"},{"id":"D009930","term":"Organic Chemicals"}]}},"hasResults":true}