Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-31 @ 7:42 AM
Study NCT ID:
NCT07442058
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-02
First Post:
2026-02-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Accelerated and Extended-iTBS Targeting Inhibitory Control in Veterans With ADHD
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001289', 'term': 'Attention Deficit Disorder with Hyperactivity'}, {'id': 'D007175', 'term': 'Impulsive Behavior'}], 'ancestors': [{'id': 'D019958', 'term': 'Attention Deficit and Disruptive Behavior Disorders'}, {'id': 'D065886', 'term': 'Neurodevelopmental Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D001519', 'term': 'Behavior'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Participants, as well as study personnel involved in administering stimulation and conducting data analysis, will be blinded to treatment conditions (active vs. sham iTBS). To maintain the integrity of the blind, a designated research assistant, who will have no other role in data collection or analysis, will be solely responsible for switching between the active and sham coils. The sham coil is specifically designed to match the active coil in appearance, sound, and scalp sensation, providing a credible sham experience, as observed in our prior studies. Blinding success is assessed with a questionnaire that inquires which condition (active or sham) the Veteran believes they received.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Active iTBS includes two extended stimulation sessions, at 90% MT, with standard parameters (50Hz triplets every 200ms), each consisting of 3,600 pulses (19 minutes), with a 30-minute intersession interval. Sham will be administered using equivalent procedures but with a sham coil.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 35}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-07-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-07-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-23', 'studyFirstSubmitDate': '2026-02-11', 'studyFirstSubmitQcDate': '2026-02-23', 'lastUpdatePostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-10-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Feasibility measured by follow-up completion', 'timeFrame': '6 weeks', 'description': 'Feasibility will be determined through follow-up completion. This will be calculated as simple proportion based on attended and scheduled follow-up sessions.'}, {'measure': 'Acceptability measured by stimulation sessions attendance', 'timeFrame': '1 day', 'description': 'Acceptability will be measured based on stimulation session attendance. This will be calculated as simple proportion based on attended and scheduled iTBS sessions.'}], 'secondaryOutcomes': [{'measure': 'Impulsivity measured by Short Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (SUPPS-P)', 'timeFrame': '6 weeks', 'description': 'The SUPPS-P is a self-report 20-item questionnaire and will be applied to assess positive urgency, negative urgency, sensation seeking, lack of premeditation, and lack of perseverance.'}, {'measure': 'Impulsivity measured by the Barratt Impulsiveness Scale (BIS-11)', 'timeFrame': '6 weeks', 'description': 'The BIS-11 is a self-report scale for the assessment of impulsivity that includes three constructs of impulsivity: motor, attention, and non-planning.'}, {'measure': 'Go/no-go task', 'timeFrame': '6 weeks', 'description': 'This task will include 150 trials. Individuals will be asked to react by pressing a button as soon as a previously designated target (black square) is presented on the computer screen (go stimulus). No behavioral reaction is required when no-go stimuli (black circle) appear. All the stimuli will be displayed in black with a white background, with the same dimensions on the computer screen for 500ms, with 1000ms as the interstimulus interval (ISI). Commission errors, omission errors, and reaction time (RT) will be assessed.'}, {'measure': 'Stop-signal task', 'timeFrame': '6 weeks', 'description': 'This task will include 150 trials, with the stimulus presented for 500ms, 1000ms ISI, and with 30% random presentation of the stop-signal. Veterans will be asked to press a specific button when a go stimulus (black circle with white arrow to the left or the right) is presented and will be requested to not click when a stop-signal (visual clue will be a red circle with white arrow to the right or the left) is shown at unpredictable intervals. The stop-signal reaction time (SSRT) and the inhibition rate (IR) will be evaluated.'}, {'measure': 'Social and Occupational Functioning measured by Social and Occupational Functioning Scale (SOFAS)', 'timeFrame': '6 weeks', 'description': 'SOFAS is a clinician-rated assessment of social and occupational functioning. The scale ranges from 1 to 100, with higher scores indicating better functioning.'}, {'measure': 'ADHD symptoms', 'timeFrame': '6 weeks', 'description': 'ASRS is an 18-item questionnaire and will be used to support the ADHD diagnosis and to identify potential iTBS-induced changes in ADHD symptoms. Each item is rated on a Likert scale from 0 (never) to 4 (very often). Part A (items 1-6) contains the most predictive items for ADHD, with a score of 14 or higher indicating a high likelihood of ADHD. Part B (items 7-18) provides additional information on symptom severity, with scores of 27 or higher being clinically significant.'}, {'measure': 'Social and Occupational Functioning measured by Sheehan Disability Scale (SDS)', 'timeFrame': '6 weeks', 'description': 'SDS is a self-report that evaluates functional impairment in family, social, and work settings. It includes a scale from 0 (no impairment) to 10 (severe impairment) for each of three domains, with a total score ranging up to 30. Higher scores indicate greater severity.'}, {'measure': 'Social and Occupational Functioning measured by Global Assessment of Functioning (GAF)', 'timeFrame': '6 weeks', 'description': 'GAF is a clinician-rated assessment of social and occupational functioning. This scale ranges from 0 to 100, with higher scores indicating better functioning.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'keywords': ['Attention Deficit Disorder with Hyperactivity', 'Intermittent Theta-Burst Stimulation', 'Inhibitory Control', 'Impulsivity', 'ADHD', 'TMS', 'Transcranial Magnetic Stimulation'], 'conditions': ['Attention Deficit Disorder With Hyperactivity']}, 'descriptionModule': {'briefSummary': 'Impaired inhibitory response manifests clinically as increased impulsivity, which leads to poorer affective, cognitive, social, and occupational functioning. Neuropsychiatric disorders prevalent among Veterans, such as Attention Deficit/Hyperactivity Disorder (ADHD), are associated with poor inhibitory control. The mainstay of clinical treatment for ADHD is psychostimulants, yet these medications have significant risks, including dependence and numerous side effects. Thus, novel and non-pharmacological therapeutic strategies are needed. Intermittent Theta Burst Stimulation, a newer form of transcranial magnetic stimulation, has emerged as a promising tool for modulating inhibitory neuronal circuits. This research proposal will investigate the feasibility and acceptability of iTBS on inhibitory control and impulsivity through a randomized controlled trial to inform clinical observations. The long-term goal is to improve impulsivity, social and occupational functioning, and enhance the quality of life for Veterans.', 'detailedDescription': 'Neuropsychiatric disorders such as Attention Deficit/Hyperactivity Disorder (ADHD), Traumatic Brain Injury (TBI), Posttraumatic Stress Disorder (PTSD), Substance Use Disorder (SUD), and suicidality impose major public health burdens. In 2021, the Centers for Disease Control and Prevention reported a 4% increase in the suicide rate, marking the largest annual rise since 2001, with 14.1 deaths per 100,000 of the United States standard population.\n\nAmong Veterans, the unadjusted suicide rate escalated from 23.3 per 100,000 in 2001 to 31.7 per 100,000 in 2020, with the highest rates (46.1 per 100,000) observed in young Veterans aged 18 to 34 years. Studies have indicated an association between ADHD and increased suicide risk. The estimated global lifetime prevalence of symptomatic ADHD in adults is 6.8%, with a higher prevalence observed in combat Veterans (10.6%). In addition, ADHD constitutes an important risk factor for both traumatic brain injury and substance use disorders. Annually, approximately 1.7 million new TBI cases are reported, exhibiting a rising trend in combat-related instances, often associated with cognitive and psychological sequelae. In the U.S., the estimated PTSD lifetime prevalence is 6.8%, with higher rates in Veterans (12.9%). SUD also stands out as another substantial contributor to the global burden of diseases, exerting a costly impact on health, productivity, crime rates, economy, and social dynamics, with a lifetime prevalence of 9.9%. A commonality across these prevalent neuropsychiatric disorders in Veterans is a deficit in inhibitory control and increased impulsivity.\n\nInhibitory control broadly describes the capacity to restrain impulsive behaviors, emotions, and thoughts, and suppress distracting stimuli. Clinically, impaired inhibitory response presents as heightened impulsivity, detrimentally impacting affective, cognitive, social, and occupational functioning. In ADHD, deficits in inhibitory control and heightened impulsivity are central, particularly in the combined and predominantly hyperactive/impulsive presentations. Neuroimaging studies have consistently identified hypoactivation in the right inferior frontal gyrus (rIFG), a region integral to response inhibition. This impairment and reduced connectivity between the rIFG and other brain regions involved in inhibitory control contribute to the impulsivity in ADHD, manifesting as poor decision-making, emotional dysregulation, and risk-taking behaviors. These deficits can exacerbate challenges in daily functioning, including difficulties in occupational settings, interpersonal relationships, and adherence to treatment regimens. In PTSD, disruptions in inhibitory brain networks compromise the ability to detach from trauma-related stimuli and associated emotional responses. This dysfunction is linked to increased arousal and impulsivity, which heighten the risk of comorbid conditions such as TBI and SUD. In SUD, the inability to disengage from pervasive drug-seeking behavior constitutes one of its main underlying mechanisms. In Veterans with SUD, impulsivity emerges as an important predictor of noncompliance with care, a crucial facet of relapse prevention. Similarly, individuals with TBI often exhibit impulsive behaviors and poor inhibition, with impaired prepotent response inhibition, adversely affecting rehabilitation and social functioning. Inhibitory response also plays a critical role in suicidality, with impulsivity working as a significant risk factor, especially in those with a history of suicide attempts. The association between impulsivity and suicide risk is notably pronounced among Veterans, wherein impaired inhibitory control has been identified as a potential predictor of suicidal behavior. Moreover, research indicates that veterans with multiple suicide attempts exhibit higher levels of impulsivity compared to those with a single attempt. ADHD is linked to a higher susceptibility to suicide, likely due to its impulsive phenotype and an increased burden of comorbidities. Notably, ADHD remains an independent risk factor for suicidal behavior after adjusting for comorbidities such as depression, SUD, and PTSD. Together, these findings highlight impaired inhibitory control and impulsivity as transdiagnostic targets of clinical relevance, particularly in ADHD, where these features are defining and predictive of broader psychiatric risk.\n\nAlthough stimulant medications (e.g., methylphenidate and related compounds) are FDA-approved first-line treatments for ADHD, their limitations are increasingly well documented in clinical and population-based studies. While effective for inattentive symptoms, their efficacy in addressing impulsivity, the primary target of this study, is comparatively limited. Moreover, stimulants have a notable range of adverse effects, including insomnia, hyporexia, irritability, and greater cardiovascular risk. In addition, the development of tachyphylaxis in some patients may attenuate therapeutic effectiveness over time, complicating long-term management. The potential for misuse, diversion, and dependency, along with concerns about long-term cost-effectiveness and stigma, further highlights the clinical and public health limitations of relying on pharmacologic strategies. Prolonged stimulant use has also been associated with increased risk of hypertension and arterial disease. These limitations underscore the critical need to evaluate safe and effective non-pharmacological interventions that can serve either as standalone treatments or as adjuncts to standard approaches, particularly for Veterans for whom medication is contraindicated, poorly tolerated, or ineffective. iTBS has a favorable safety profile, with side effects being mostly mild and transient (e.g., scalp discomfort, headache, or facial twitching). The risk of seizure with iTBS is comparable to that of conventional TMS protocols, with both estimated to carry an incidence \\<0.01% when administered according to established safety guidelines, as planned in this study. Given the theoretical risk associated with concurrent use of TMS and stimulants, this trial will implement careful monitoring to ensure participant\'s safety. While this application focuses on developing non-invasive brain stimulation, the proposal as outlined here would also serve as an adjunct to other non-medication options for ADHD, such as cognitive rehabilitation.\n\nTranscranial magnetic stimulation (TMS) is an effective treatment for depression, smoking cessation, and OCD, and has promise in treating PTSD. Concerning ADHD, an increase in striatal dopamine, equivalent to the effects of dextroamphetamine, was observed following TMS treatment. Standard TMS has been investigated as a treatment for ADHD with mixed results. Left prefrontal TMS yields improvements in inattentive symptoms of ADHD, while other trials indicate that the right prefrontal cortex is underactive and might be a more effective target. TMS over the right prefrontal cortex demonstrated benefits in modulating inhibitory control and attention. fMRI studies demonstrate hypoactivation of the right prefrontal cortex during inhibitory control in individuals with ADHD. This lateralization likely explains why TMS to the left dorsolateral prefrontal cortex might have yielded limited responses. Regardless, questions of laterality on target underscore the necessity for precision approaches. In addition, conventional TMS protocols, which involve daily sessions for up to six weeks, pose a substantial time and financial burden. In this context, there has been increased adoption of intermittent Theta Burst Stimulation (iTBS), a second-generation TMS modality. iTBS generated enhanced cortical excitability, facilitating synaptic connections through putative long-term potentiation-like effects. iTBS also stands out given its favorable safety profile and brief duration. To date, few trials have examined TBS for inhibitory control, particularly within the context of nicotine addiction, with positive outcomes targeting the rIFG. The right IFG exerts a pivotal role in modulating inhibitory response, notably its prepotent component. This cortical region is a key node within the inhibitory control circuitry, in conjunction with the pre-supplementary motor area and striatum. Improved inhibitory responses have been associated with enhanced top-down mediation facilitated via the rIFG. With these factors in mind, this proposal will assess feasibility and acceptability of iTBS on inhibitory control through a pilot randomized controlled trial, with precision functional connectivity targeting of the IFG. The investigators\' design, featuring a high pulse dose concentrated within a single day, reflects the experience delivering non-invasive brain stimulation to Veterans, and leverages recent advances in accelerated TMS that permit, for the first time, large "doses" of TMS in a short period, which the investigators hope will increase access. Given the prevalence of inhibitory control deficits across neuropsychiatric disorders in Veterans, coupled with the challenges related to psychostimulants, there is compelling empirical justification to pursue accelerated and extended iTBS as a novel therapeutic modality.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of ADHD predominantly hyperactive-impulsive or combined, as outlined in the DSM-5-TR criteria\n* Maintenance of clinical symptoms despite receiving stable treatment for a minimum of 6 weeks before the study procedures\n* Capability to comprehend and provide informed consent\n* For safety reasons, participants must meet established screening criteria to ensure safety during Magnetic Resonance Imaging (MRI) scans\n\n * This precaution is taken due to the novel application of iTBS in this specific population, as MRI involves exposure to magnetic fields similar in intensity to those emitted from the stimulation coil\n* As such, participants must not have the following, unless the devices are MRI-safe:\n\n * cardiac pacemaker\n * implanted devices (such as deep brain stimulators)\n * metal in the brain\n * cervical spinal cord, or upper thoracic spinal cord level\n* In addition, eligible Veterans must also be able and willing to comply with all study procedures and visits\n* Throughout the study, pharmacologic and psychotherapeutic regimens will tentatively remain unchanged\n\nExclusion Criteria:\n\n* Primary psychotic disorders, bipolar I disorder, ongoing severe substance use disorders, or active suicidality\n* Non-MRI safe cardiac pacemakers, implanted devices, or metallic implants at the upper thoracic spine level or higher\n* Any of the Transcranial Magnetic Stimulation (TMS) specific exclusion criteria, including:\n\n * pregnancy\n * lactation\n * planning pregnancy during period of study\n * history of moderate or severe traumatic brain injury\n * active unstable medical conditions\n * CNS tumors\n * seizures\n * cerebrovascular disease\n * other severe neurological disorders\n* Additional exclusion criteria include the presence of any other condition or circumstance that, as determined by the investigator team, has the potential to prevent study completion or introduce confounding effects in outcome assessments'}, 'identificationModule': {'nctId': 'NCT07442058', 'acronym': 'ACHIEVE', 'briefTitle': 'Accelerated and Extended-iTBS Targeting Inhibitory Control in Veterans With ADHD', 'organization': {'class': 'FED', 'fullName': 'VA Office of Research and Development'}, 'officialTitle': 'ACHIEVE: Accelerated and Extended-rTMS to Heighten Inhibitory Control Engagement in Veterans', 'orgStudyIdInfo': {'id': 'RRD4-003-25M'}, 'secondaryIdInfos': [{'id': '1I21RD002067-01A1', 'type': 'OTHER_GRANT', 'domain': 'RRD&T'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Active Stimulation', 'description': 'Active iTBS includes two extended stimulation sessions, at 90% MT, with standard parameters (50Hz triplets every 200ms), each consisting of 3,600 pulses (19 minutes), with a 30-minute intersession interval.', 'interventionNames': ['Device: Intermittent Theta-Burst Stimulation']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham Stimulation', 'description': 'Sham will be administered using equivalent procedures but with a sham coil. The sham coil is specifically designed to match the active coil in appearance, sound, and scalp sensation, providing a credible sham experience, as observed in our prior studies.', 'interventionNames': ['Device: Sham Stimulation']}], 'interventions': [{'name': 'Intermittent Theta-Burst Stimulation', 'type': 'DEVICE', 'otherNames': ['iTBS'], 'description': 'Theta Burst Stimulation is a second-generation TMS modality. iTBS enhances cortical excitability, facilitating synaptic connections through putative long-term potentiation-like effects. In addition, iTBS also stands out given its favorable safety profile and its brief administration time.', 'armGroupLabels': ['Active Stimulation']}, {'name': 'Sham Stimulation', 'type': 'DEVICE', 'otherNames': ['Sham'], 'description': 'Sham will be administered using equivalent procedures but with a sham coil.', 'armGroupLabels': ['Sham Stimulation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02908-4734', 'city': 'Providence', 'state': 'Rhode Island', 'country': 'United States', 'contacts': [{'name': 'Kate J Barnabe, MHA', 'role': 'CONTACT', 'email': 'Kate.Barnabe@va.gov', 'phone': '401-273-7100', 'phoneExt': '16272'}, {'name': 'Camila Souza A Cosmo, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Providence VA Medical Center, Providence, RI', 'geoPoint': {'lat': 41.82399, 'lon': -71.41283}}], 'centralContacts': [{'name': 'Camila Souza A Cosmo, PhD', 'role': 'CONTACT', 'email': 'CamilaSouza.Cosmo@va.gov', 'phone': '(401) 273-7100'}, {'name': 'Emily M Aiken, MA BS', 'role': 'CONTACT', 'email': 'emily.aiken@va.gov', 'phone': '(401) 273-7100', 'phoneExt': '6254'}], 'overallOfficials': [{'name': 'Camila Souza A Cosmo, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Providence VA Medical Center, Providence, RI'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'VA Office of Research and Development', 'class': 'FED'}, 'responsibleParty': {'type': 'SPONSOR'}}}}