Ignite Creation Date:
2025-12-24 @ 7:16 PM
Ignite Modification Date:
2026-02-21 @ 10:01 PM
Study NCT ID:
NCT02356003
Status:
COMPLETED
Last Update Posted:
2020-10-29
First Post:
2015-01-31
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Transcranial Magnetic Stimulation for Children With Tourette's Syndrome
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005879', 'term': 'Tourette Syndrome'}, {'id': 'D020323', 'term': 'Tics'}], 'ancestors': [{'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D013981', 'term': 'Tic Disorders'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D065886', 'term': 'Neurodevelopmental Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'fmacmast@ucalgary.ca', 'phone': '403-955-2784', 'title': 'Frank MacMaster', 'organization': 'University of Calgary'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'This was a pilot open label trial of rTMS and as such subject to the standard limitations of all pilot intervention studies.'}}, 'adverseEventsModule': {'timeFrame': 'The three weeks of the intervention and the week following.', 'description': 'We have a scale for tolerability and adverse events that we use for all TMS studies.', 'eventGroups': [{'id': 'EG000', 'title': 'Low Frequency rTMS', 'description': 'Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Yale Global Tic Severity Scale', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Low Frequency rTMS', 'description': 'Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '64.40', 'spread': '19.83', 'groupId': 'OG000'}]}]}, {'title': 'Post-rTMS', 'categories': [{'measurements': [{'value': '26.40', 'spread': '14.86', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Four weeks', 'description': "Measure of tic severity using the Yale Global Tic Severity Scale (YGTSS). This is the standard measure for studies of Tourette's syndrome. The Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater severity of tics.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We stopped recruitment at 10 as the study ran out of money.'}, {'type': 'SECONDARY', 'title': 'Glutamate Concentration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Low Frequency rTMS', 'description': 'Ten children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '14.2', 'spread': '1.73', 'groupId': 'OG000'}]}]}, {'title': 'Post-rTMS', 'categories': [{'measurements': [{'value': '13.4', 'spread': '1.38', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Four weeks', 'description': 'Glutamate concentration in the supplementary motor area', 'unitOfMeasure': 'mM', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We stopped recruitment at 10 as the study ran out of money.'}, {'type': 'SECONDARY', 'title': 'Functional Connectivity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Low Frequency rTMS', 'description': 'Ten children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.89', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Four weeks', 'description': 'Functional connectivity between the supplementary motor area and primary motor cortex as measured with resting state functional magnetic resonance imaging (rs-fMRI). T-value is the fMRI statistic that shows the level of connectivity. The higher the T-value, the greater the level of connectivity.', 'unitOfMeasure': 'T-value', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Low Frequency rTMS', 'description': 'Ten children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Low Frequency rTMS', 'description': 'Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).\n\nLow frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '11.524', 'spread': '1.995', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '10', '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': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Canada', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Yale Global Tic Severity Scale (YGTSS)', 'classes': [{'categories': [{'measurements': [{'value': '64.40', 'spread': '19.83', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'The Yale Global Tic Severity Scale (YGTSS) quantifies the severity of tic symptoms in individuals aged 6-17 years. The YGTSS is a semi-structured interview where individuals are asked to rate the severity of their tic symptoms (motor and vocal; number, frequency, intensity, complexity, and interference). There is also an impairment scale, where the participant rates how tics impact their daily life. The Total Tic Severity Score has a range of 0-50, and the Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater tic severity.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2014-12-17', 'size': 241262, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-02-11T15:19', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-10', 'completionDateStruct': {'date': '2018-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-10-07', 'studyFirstSubmitDate': '2015-01-31', 'resultsFirstSubmitDate': '2020-02-11', 'studyFirstSubmitQcDate': '2015-01-31', 'lastUpdatePostDateStruct': {'date': '2020-10-29', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-03-31', 'studyFirstPostDateStruct': {'date': '2015-02-04', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-04-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Yale Global Tic Severity Scale', 'timeFrame': 'Four weeks', 'description': "Measure of tic severity using the Yale Global Tic Severity Scale (YGTSS). This is the standard measure for studies of Tourette's syndrome. The Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater severity of tics."}], 'secondaryOutcomes': [{'measure': 'Glutamate Concentration', 'timeFrame': 'Four weeks', 'description': 'Glutamate concentration in the supplementary motor area'}, {'measure': 'Functional Connectivity', 'timeFrame': 'Four weeks', 'description': 'Functional connectivity between the supplementary motor area and primary motor cortex as measured with resting state functional magnetic resonance imaging (rs-fMRI). T-value is the fMRI statistic that shows the level of connectivity. The higher the T-value, the greater the level of connectivity.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Tourette Syndrome', 'Children', 'Tics'], 'conditions': ['Tourette Syndrome']}, 'descriptionModule': {'briefSummary': 'Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. For these reasons, new interventions are needed. The investigators will target a brain region involved in tics called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, the investigators will inhibit the activity, in a similar way to the tic suppression that develops with age. The investigators propose the following objectives: (Aim 1) The investigators hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators further hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area, and changes in the functional connectivity between the supplementary motor area and primary motor cortex. Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (five times a week for three weeks). After the three weeks, they will look for changes in tic severity and brain chemistry and function. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.', 'detailedDescription': 'Background Tourette syndrome is very common. It affects over 80,000 Canadian youth. Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. Medications for Tourette syndrome carry significant risk of side effects. Behavioral treatments, like habit reversal therapy, show promise and are safe, but are difficult to apply to younger children. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. Finally, neither medication nor behavior therapies directly target the root cause of the tics. For these reasons, new interventions are needed.\n\nSpecific Objectives The investigators will target a key brain region involved in tics. It is called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, they will inhibit the activity of that brain region, in a similar way to the tic suppression that develops with age.\n\nThe investigators propose the following specific objectives:\n\n(Aim 1) The investigators will characterize the effect of low frequency repetitive transcranial magnetic stimulation of the supplementary motor area on Tourette syndrome symptoms. They hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area.\n\n(Aim 2) The investigators will identify the changes in brain metabolites (glutamate and GABA) and functional connectivity caused by low frequency repetitive transcranial magnetic stimulation that normalize brain activity. They hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area. This will be assessed with proton magnetic resonance spectroscopy, potentiation of GABAergic neurotransmission assessed with short-interval cortical inhibition, and changes in the functional connectivity between the supplementary motor area and primary motor cortex.\n\nMethods Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). The investigators will assess the key variables with interviews and brain imaging of the children before and after the three-week intervention. After the three weeks, they will look for changes in tic severity and brain chemistry and function.\n\nExpected Results The investigators have pioneered transcranial magnetic stimulation applications in child and adolescent populations. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['CHILD'], 'maximumAge': '12 Years', 'minimumAge': '7 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Males\n* Right-handed\n\nExclusion Criteria:\n\n* Female\n* Left-handed\n* Comorbid Attention Deficit Hyperactivity Disorder'}, 'identificationModule': {'nctId': 'NCT02356003', 'acronym': 'TICS', 'briefTitle': "Transcranial Magnetic Stimulation for Children With Tourette's Syndrome", 'organization': {'class': 'OTHER', 'fullName': 'University of Calgary'}, 'officialTitle': "TICS: Transcranial Magnetic Stimulation for Children With Tourette's Syndrome", 'orgStudyIdInfo': {'id': 'REB14-1839'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Low frequency rTMS', 'description': 'Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks).', 'interventionNames': ['Device: Low frequency repetitive transcranial magnetic stimulation']}], 'interventions': [{'name': 'Low frequency repetitive transcranial magnetic stimulation', 'type': 'DEVICE', 'description': 'Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.', 'armGroupLabels': ['Low frequency rTMS']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'T2N 4N1', 'city': 'Calgary', 'state': 'Alberta', 'country': 'Canada', 'facility': 'University of Calgary', 'geoPoint': {'lat': 51.05011, 'lon': -114.08529}}], 'overallOfficials': [{'name': 'Frank p MacMaster, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Calgary'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Calgary', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor', 'investigatorFullName': 'Frank MacMaster, PhD', 'investigatorAffiliation': 'University of Calgary'}}}}