MODELING OBSESSIVE COMPULSIVE DISORDER AND EXPLORING TREATMENT RESPONSE USING INNOVATIVE THERAPIES AND STEM CELLS

March 18, 2026 updated by: BERNARDO DELL'OSSO, ASST Fatebenefratelli Sacco

FROM DISEASE MODELING TO THE MOLECULAR BASES OF TREATMENT RESPONSE FOR OBSESSIVE-COMPULSIVE DISORDER USING INNOVATIVE THERAPIES AND PATIENT-DERIVED PLURIPOTENT STEM CELLS

This study focuses on people with obsessive-compulsive disorder (OCD) who do not respond well to standard treatments. Researchers aim to understand why some patients respond to medications or brain stimulation therapies, while others do not. The study will include 60 patients grouped by their treatment response:

  1. Those who respond to medications
  2. Those who respond to transcranial magnetic stimulation (TMS)
  3. Those who do not respond to either Blood samples will be used to create nerve cells in the lab, allowing scientists to study how these cells react to treatments and brain stimulation. By combining clinical information with lab findings, the goal is to discover biological markers that predict which therapy will work best for each person. This research hopes to improve personalized treatment options for OCD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Adults (18-65 years old) with obsessive-compulsive disorder (OCD) recruited at two specialized clinics in Milan (Luigi Sacco Hospital) and Monza (IRCCS Fondazione San Gerardo Monza). After a complete explanation of the study, everyone will provide written informed consent and have a diagnostic interview to confirm OCD. People with seizures/epilepsy or certain implanted devices (e.g., pacemaker, intracranial metal clips) will not be enrolled.

Procedures:

  1. Initial assessments: Participants complete standard questionnaires and tests about OCD symptoms, mood, anxiety, and thinking (e.g., Y-BOCS, HDRS, HARS, MMSE, CANTAB, CGI). Basic information (age, sex, education, medical history, current medications) is collected in an anonymized electronic form.

  2. Grouping by medication response:

    Responders (20 people): OCD symptoms improve with serotonin reuptake inhibitors (SRIs).

    Treatment-resistant (40 people): OCD symptoms did not improve after multiple SRI trials (including SSRIs and clomipramine at recommended doses).

  3. Randomized brain stimulation for treatment-resistant OCD:

    The 40 treatment-resistant participants are randomly assigned (1:1) to Theta-Burst TMS (TBS) or Deep TMS (d-TMS), following established safety guidelines.

    Medications remain stable during TMS. Symptom changes are measured with the Y-BOCS at baseline and follow-up. Participants are classified as responders or non-responders to TBS or d-TMS.

    After treatment, people fall into five subgroups: SRI Responders, d-TMS Responders, TBS Responders, d-TMS Non-Responders, TBS Non-Responders.

  4. Blood samples and lab modeling:

    A small blood sample is used to create patient-derived stem cells (hiPSCs) and then striatal neurons (medium spiny neurons, MSNs) in the lab.

    These neurons help us study how brain cells from different patient groups respond to medicines and stimulation.

  5. Mimicking brain stimulation in the lab:

    Researchers use optogenetics (safe light pulses) to activate the lab-grown neurons, mirroring the effects of TMS.

    They also use well-known medicines that turn up or down dopamine signaling (e.g., D1/D2 agonists/antagonists) to see how neurons react.

    Changes in synaptic proteins and cell activity are measured with standard lab techniques.

  6. Gene activity (transcriptomics):

Using RNA sequencing, the team looks at which genes are "on" or "off" in neurons from different patient groups-before and after light stimulation-to discover molecular signatures linked to treatment response or resistance.

Findings are checked and confirmed with additional lab tests.

Study results analysis

The study includes 60 participants in total. Data are analyzed with standard statistical methods to compare groups and treatments. Lab experiments use multiple independent preparations to ensure reliable results.

Study outcomes:

By combining careful clinical assessments with cutting-edge cell models, this study aims to discover biological markers that can predict who will benefit from medicines and from innovative TMS protocols (TBS or d-TMS)-helping move toward more personalized care for OCD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20100
        • ASST Fatebenefratelli Sacco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • diagnosis of Obsessive-Compulsive Disorder (according to DSM-5; APA, 2013); both sexes; age ≥ 18 years and ≤ 65 years, ability to provide valid written informed consent; for patients classified as responders to pharmacological treatment, a clinical history of at least one pharmacological trial with an SRI for a minimum of 6 weeks and evidence of treatment response, defined as a 30% reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score (Goodman et al., 1989) relative to the patient's baseline; for patients classified as resistant to pharmacological treatment [TR], clear evidence of treatment resistance, defined as the absence of a significant clinical response after at least two treatment trials with selective serotonin reuptake inhibitors (SSRIs) and one trial with clomipramine, each administered for a minimum of 12 weeks at the maximum recommended dose (Pallanti et al., 2002).

Exclusion Criteria:

  • inability to provide informed consent; no clinical history of treatment with SRI medications; clinical history of epilepsy or seizures; presence of a pacemaker, removable metal prostheses, implanted medical pumps, or intracranial metal clips.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Deep TMS
This arm includes patients classified as resistant to pharmacological treatment, clear evidence of treatment resistance (defined as the absence of a significant clinical response after at least two treatment trials with SSRIs and one trial with clomipramine each administered for a minimum of 12 weeks at the maximum recommended dose). Patients will undergo d-TMS protocol for 5 weeks of daily treatments, 5 days a week and 4 treatments during the 6th week, and a 4-week follow-up phase.
Device: deep transcranial magnetic stimulation (dTMS)
The d-TMS protocol will be performed at the treatment-resistant disorders clinic, IRCCS San Gerardo Monza, and will consist of 5 weeks of daily treatments, 5 days a week and 4 treatments during the 6th week, and a 4-week follow-up phase, following most recent clinical studies. d-TMS will be administered using a TMS stimulator equipped with an H-shaped coil (Harmelech et al., 2021). The coil will be placed 4 cm anterior to the foot motor cortex and used at 100% of the leg resting motor threshold (RMT), defined as the coil position that elicited the minimal involuntary contractions of the feet (3 of 6 attempts). The stimulation of the area localized 4 cm anterior to the foot motor cortex targets the dorsal medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) bilaterally. Patients will receive 20 Hz d-TMS at 100% of RMT, with 2-second pulse trains and 20-second intertrain intervals, for a total of 50 trains and 2,000 pulses per session.
Experimental: TBS protocol
This arm includes patients classified as resistant to pharmacological treatment, clear evidence of treatment resistance (defined as the absence of a significant clinical response after at least two treatment trials with SSRIs and one trial with clomipramine each administered for a minimum of 12 weeks at the maximum recommended dose). Patients from this group will undergo the TBS protocol at the OCD clinic, ASST Fatebenefratelli Sacco of Milan, consisting in one week of daily treatments and a 4-weeks follow-up phase.
Device: Theta burst stimulation (TBS)
TBS will be administered using a Magstim Rapid2 stimulator. 3-pulse 50-Hz bursts will be given to patients' left orbitofrontal cortex every 200 ms (at 5 Hz) at an intensity of 80% of the active motor threshold, defined as the coil position that elicited a right thumb movement while stimulating the left primary motor cortex. The treatment will consist of 2 sessions per day, thirty minutes apart, for 5 days in a week. Following the parameters of previous studies, each session will deliver a burst of three pulses at 50 Hz and repeated every 200 ms (at 5 Hz) for a total of 600 pulses lasting 40s (Oberman et al., 2011). A total of 1200 pulses will be delivered per day.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score
Time Frame: Baseline to 10 weeks (end of treatment and follow-up)
The primary outcome is the change in Y-BOCS total score from baseline to the end of treatment, used to assess clinical response to TBS versus d-TMS in treatment-resistant OCD patients.
Baseline to 10 weeks (end of treatment and follow-up)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinical response rate
Time Frame: Baseline to end of follow-up (4 weeks post-treatment)
Proportion of participants achieving a reduction ≥20% in Y-BOCS total score after TMS treatment.
Baseline to end of follow-up (4 weeks post-treatment)
Change in Clinical Global Impression (CGI) scores
Time Frame: Baseline to 10 weeks
Change in CGI-Severity and CGI-Improvement scores from baseline to post-treatment.
Baseline to 10 weeks
Change in Hamilton Depression Rating Scale (HDRS)
Time Frame: Baseline to end of follow-up (4 weeks post-treatment)
Change in depressive symptom severity measured by HDRS.
Baseline to end of follow-up (4 weeks post-treatment)
Change in Hamilton Anxiety Rating Scale (HARS)
Time Frame: Baseline to end of follow-up (4 weeks post-treatment)
Change in anxiety symptom severity measured by HARS.
Baseline to end of follow-up (4 weeks post-treatment)
Molecular and cellular characterization of patient-derived neurons
Time Frame: From baseline (sample collection) to completion of laboratory analyses (up to 36 months)
Assessment of morphological, biochemical, and transcriptomic profiles of hiPSC-derived medium spiny neurons from participants, including differential gene expression and response to stimulation.
From baseline (sample collection) to completion of laboratory analyses (up to 36 months)
Treatment response classification
Time Frame: Baseline to end of follow-up (4 weeks post-treatment)
Classification of participants into responders and non-responders to TBS or d-TMS based on predefined Y-BOCS thresholds.
Baseline to end of follow-up (4 weeks post-treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ASST Fatebenefratelli Sacco

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fondazione IRCCS San Gerardo dei Tintori
Istittuo ricerca carattere Sceintifico Fatenefratelli Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 29, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 18, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 23, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RF-2021-12374133

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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