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

NCT07488663 | Enrolling By Invitation

• 1 other identifier: RF-2021-12374133
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Those who respond to medications
2. 2.Those who respond to transcranial magnetic stimulation (TMS)
3. 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.

Conditions

Obsessive - Compulsive Disorder

Keywords

TRANSCRANIAL MAGNETIC STIMULATION; HUMAN PLURIPOTENT STEM CELLS; OBSESSIVE COMPULSIVE DISORDER

Outcome Measures

Primary Outcomes (1)

• Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score

  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 Outcomes (6)

• Clinical response rate

  Baseline to end of follow-up (4 weeks post-treatment)

• Change in Clinical Global Impression (CGI) scores

  Baseline to 10 weeks

• Change in Hamilton Depression Rating Scale (HDRS)

  Baseline to end of follow-up (4 weeks post-treatment)

• Change in Hamilton Anxiety Rating Scale (HARS)

  Baseline to end of follow-up (4 weeks post-treatment)

• Molecular and cellular characterization of patient-derived neurons

  From baseline (sample collection) to completion of laboratory analyses (up to 36 months)

Study Arms (2)

Deep TMS

EXPERIMENTAL

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)

TBS protocol

EXPERIMENTAL

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)

Interventions

deep transcranial magnetic stimulation (dTMS) DEVICE

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.

Deep TMS

Theta burst stimulation (TBS) DEVICE

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.

TBS protocol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• ASST Fatebenefratelli Sacco: lead
• Fondazione IRCCS San Gerardo dei Tintori: collaborator
• Istittuo ricerca carattere Sceintifico Fatenefratelli Brescia: collaborator

Study Sites (1)

Asst Fatebenefratelli Sacco

Milan, 20100, Italy

Location

Related Publications (8)

• Vadodaria KC, Ji Y, Skime M, Paquola A, Nelson T, Hall-Flavin D, Fredlender C, Heard KJ, Deng Y, Le AT, Dave S, Fung L, Li X, Marchetto MC, Weinshilboum R, Gage FH. Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons. Mol Psychiatry. 2019 Jun;24(6):795-807. doi: 10.1038/s41380-019-0363-y. Epub 2019 Jan 30.

  PMID: 30700803 BACKGROUND

• Shoaib M, Giacopuzzi E, Pain O, Fabbri C, Magri C, Minelli A, Lewis CM, Gennarelli M. Investigating an in silico approach for prioritizing antidepressant drug prescription based on drug-induced expression profiles and predicted gene expression. Pharmacogenomics J. 2021 Feb;21(1):85-93. doi: 10.1038/s41397-020-00186-5. Epub 2020 Sep 17.

  PMID: 32943772 BACKGROUND

• Burguiere E, Monteiro P, Feng G, Graybiel AM. Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science. 2013 Jun 7;340(6137):1243-6. doi: 10.1126/science.1232380.

  PMID: 23744950 BACKGROUND

• Marcatili M, Marsoner F, D'Agostino A, Karnavas T, Bottai D, Scarone S, Conti L. Establishment of an induced pluripotent stem cell (iPSC) line from a patient with Clozapine-responder Schizophrenia. Stem Cell Res. 2016 Nov;17(3):630-633. doi: 10.1016/j.scr.2016.11.009. Epub 2016 Nov 9.

  PMID: 27934596 BACKGROUND

• Marcatili M, Sala C, Dakanalis A, Colmegna F, D'Agostino A, Gambini O, Dell'Osso B, Benatti B, Conti L, Clerici M. Human induced pluripotent stem cells technology in treatment resistant depression: novel strategies and opportunities to unravel ketamine's fast-acting antidepressant mechanisms. Ther Adv Psychopharmacol. 2020 Nov 2;10:2045125320968331. doi: 10.1177/2045125320968331. eCollection 2020.

  PMID: 33224469 BACKGROUND

• Dell'Osso B, Mundo E, D'Urso N, Pozzoli S, Buoli M, Ciabatti M, Rosanova M, Massimini M, Bellina V, Mariotti M, Altamura AC. Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord. 2009 Feb;11(1):76-81. doi: 10.1111/j.1399-5618.2008.00651.x.

  PMID: 19133969 BACKGROUND

• Arici C, Benatti B, Cafaro R, Cremaschi L, Degoni L, Pozzoli S, Oldani L, Molteni L, Giorgetti F, Priori A, Vigano C, Dell'Osso B. A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. CNS Spectr. 2022 Feb;27(1):93-98. doi: 10.1017/S1092852920001807. Epub 2020 Sep 4.

  PMID: 32883389 BACKGROUND

• Dell'Osso B, Nicolini H, Lanzagorta N, Benatti B, Spagnolin G, Palazzo MC, Marazziti D, Hollander E, Fineberg N, Stein DJ, Pallanti S, Van Ameringen M, Lochner C, Hranov G, Karamustafalioglu O, Hranov L, Zohar J, Denys D, Altamura AC, Menchon JM. Cigarette smoking in patients with obsessive compulsive disorder: a report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS). CNS Spectr. 2015 Oct;20(5):469-73. doi: 10.1017/S1092852915000565. Epub 2015 Sep 9.

  PMID: 26349811 BACKGROUND

MeSH Terms

Conditions

Compulsive Personality Disorder; Obsessive-Compulsive Disorder

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Anxiety Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study with no masking. Participants, care providers, and investigators are aware of the assigned intervention (TBS or d-TMS), as the procedures differ in administration and cannot be feasibly blinded. No independent blinded outcome assessors are used.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FULL PROFESSOR OF PSYCHIATRY

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 23, 2026
• Study Start: April 30, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 29, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)