Improving Obsessive-compulsive Disorder Treatments: From Lesions to Neuromodulation Targets
NCT Number: NCT06490965
Acronym: ON-TARGET
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Obsessive-Compulsive Disorder
Interventions: OTHER: Repetitive Transcranial Magnetic Stimulation|OTHER: Neuronavigation|OTHER: Magnetic Resonance Imaging
Sponsor: Fundacao Champalimaud
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 32
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2026-12-31
Locations: Champalimaud Foundation, Lisbon, 1400-038, Portugal

Summary:
While in most cases of obsessive-compulsive disorder (OCD) a cause cannot be identified, this syndrome may develop as a consequence of focal brain lesions. Neuropsychiatric disorders secondary to brain insults are open windows to understand their underlying neurobiology. Different neuroimaging analysis methods, including pooled lesion topography and lesion network mapping, can be used to study lesional neuropsychiatric syndromes, including OCD. If successful, these strategies can also reveal new neuromodulation treatment targets, including for transcranial magnetic stimulation (TMS). Indeed, TMS targets to treat depression evolved from evidence extracted from lesional studies that were then refined and validated. For OCD treatment with TMS, already approved by the FDA and European Commission, targets were defined using a distinct approach, not involving causal brain lesions, which may contribute to lower than desirable remission rates. Lesional OCD is characterized by specific dysfunctional brain circuits. These circuits may be effectively targeted by TMS, which may optimize treatment of OCD. To address these hypotheses, we will test the therapeutic benefits of optimizing brain targets for the currently used TMS treatment of OCD, using information from the lesional-OCD brain network namely refining the target in the medial orbitofrontal cortex, bilaterally. Specifically, we will conduct a randomized clinical interventional study, using TMS to treat patients with OCD with inadequate response to other treatments, comparing, within the approved protocol for OCD treatment, the most frequently used stimulation site with a new target, adjusted according to the connectivity of lesions associated with the occurrence of OCD. If successful, our results may have immediate clinical implications in OCD treatment, as it will contribute to refine current therapeutic TMS strategies for OCD and defining new clinical research strategies in this domain.

Primary Outcome Measures: Yale-Brown Obsessive Compulsive Scale - II (YBOCS-II), Assessment instrument for the severity of OCD symptoms; scores can range from 0-50; higher scores mean worse outcome., Before and after TMS treatment cycle. The latter will be considered the primary endpoint (end-of-study visit) and will occur preferably between 2-3 weeks after last TMS session.
Secondary Outcome Measures: State Trait Anxiety Inventory (STAI), Self-report instrument that measures anxiety in the dimensions of state anxiety and trait anxiety that often occur in comorbidity with OCD symptoms; scores for both state anxiety and trait anxiety can range from 20-80; higher scores mean worse outcome for both state anxiety and trait anxiety., Before and after TMS treatment cycle. The latter will be considered the primary endpoint (end-of-study visit) and will occur preferably between 2-3 weeks after last TMS session.|Beck Depression Inventory II (BDI-II), Self-report scale that measures the severity of depressive symptoms often occurring in comorbidity with OCD symptoms; scores can range from 0-63; higher scores mean worse outcome., Before TMS treatment cycle. Every 5 TMS treatment cycle visits (1st, 6th, 11th, 16th, 21st, and 26th visits). After TMS treatment cycle, i.e., 2-3 weeks after last TMS session.|Obsessive-Compulsive Inventory - Revised (OCI-R), Self-report scale that allows the assessment of dimensions present in OCD; scores can range from 0-72; higher scores mean worse outcome., Before TMS treatment cycle. Every 5 TMS treatment cycle visits (1st, 6th, 11th, 16th, 21st, and 26th visits). After TMS treatment cycle, i.e., 2-3 weeks after last TMS session.|Young Mania Rating Scale (YMRS), Assessment instrument for the severity of manic symptoms, a possible neuropsychiatric adverse effect of TMS; scores can range from 0-60; higher scores mean worse outcome., Before TMS treatment cycle. Every 5 TMS treatment cycle visits (1st, 6th, 11th, 16th, 21st, and 26th visits). After TMS treatment cycle, i.e., 2-3 weeks after last TMS session.|World Health Organization Five Well-Being Index (WHO-5), Self-report scale that measures subjective quality of life based on mood, vitality, and interest in things in general; scores can range from 0-25; higher scores mean better outcome., Before TMS treatment cycle. Every 5 TMS treatment cycle visits (1st, 6th, 11th, 16th, 21st, and 26th visits). After TMS treatment cycle, i.e., 2-3 weeks after last TMS session.