Improving Obsessive-compulsive Disorder Treatments: from Lesions to Neuromodulation Targets

Sponsor
Fundacao Champalimaud
Study ID
NCT06490965
Status
Recruiting
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Conditions

  • Obsessive-Compulsive Disorder

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Repetitive Transcranial Magnetic Stimulation — OTHER
    Transcranial Magnetic Stimulation (TMS) involves generating a magnetic field with specific spatial and temporal properties, allowing the induction of electric current in conductive material near this field. The electro-physiological principle of TMS is based on placing a coil over the skull that will induce a magnetic field generating action potentials in neuronal tissue in response to each TMS pulse. The repetitive application of TMS pulses (rTMS) allows for the modulation of neuronal excitability for a period after rTMS, ranging from inhibition, in the case of low frequencies (\~1 Hz), or facilitation if high frequencies (equal to or greater than 5 Hz) are used.
  • Neuronavigation — OTHER
    Neuronavigation is a non-invasive method that allows the creation of computerized three-dimensional models of brain structures based on neuroimaging exams of each individual (e.g., cranial magnetic resonance imaging). As such, this method has been used for various purposes, such as assisting in neurosurgery or mapping functional regions of the brain, but also in the context of TMS (Transcranial Magnetic Stimulation). In this latter area, its use as support for TMS has been employed for therapeutic, diagnostic, and research purposes. The neuronavigation system consists of several components, namely a locating camera, locators for the TMS coil, an adjustable headband with locators, a calibration system for these elements, and the neuronavigation software, which is installed on a supporting computer.
  • Magnetic Resonance Imaging — OTHER
    Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging technique that generates detailed images of the internal structures of the body using a strong magnetic field and radio waves. It provides high-resolution images of soft tissues, such as organs, muscles, and the brain, helping doctors diagnose and monitor various conditions, including injuries, tumors, and neurological disorders. MRI is particularly useful because it does not involve ionizing radiation, making it safer for patients than other imaging methods like X-rays or CT scans.

Study Details

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.

Key Dates

First listed
Jul 8, 2024
Start date
Nov 7, 2024
Status verified
Sep 2024
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
32 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A
    Standard of care rTMS protocol, i.e., daily frequency of repetitive excitatory TMS at 20 Hz of the medial prefrontal cortex - approximate duration of each session between 40-60 minutes.
  • Experimental: Arm B
    Standard of care rTMS protocol, i.e., daily frequency of repetitive excitatory TMS at 20 Hz with adjustment of the stimulation site to primarily target the bilateral medial orbitofrontal cortex.

Primary Outcome Measure

Yale-Brown Obsessive Compulsive Scale - II (YBOCS-II) [ Time Frame: 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. ]

Central Contacts

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