TMS for Exposure Therapy Resistant OCD

NCT05331937 | Recruiting Phase 3 DMC

• 1 other identifier: 2021.0670 - NL78930.029.21
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 8

Brief Summary

TETRO is a multi-center placebo-controlled double-blind randomized controlled trial with an intervention phase of 5-7 weeks and a follow-up phase of 12 months in 250 adult (18 years and older) OCD patients who show no/insufficient response to ERP, aiming to establish the cost-effectiveness of low frequency (1 Hz) rTMS to the pre-SMA (compared to sham rTMS to the pre-SMA) as adjuvant treatment to exposure with response prevention (ERP). The treatment consists of 4 times/week rTMS combined with ERP for at least 5 weeks (20 sessions), with optional extension phase of 1 or 2 weeks (maximum of 28 sessions in total).

Conditions

1 Hz Real rTMS to the Pre-SMA; 1 Hz Sham rTMS to the Pre-SMA

Outcome Measures

Primary Outcomes (1)

• Y-BOCS

  The severity of OCD as measured by the Yale-Brown Obsessive-Compulsive Scale Y-BOCS I

  The primary endpoint is the difference between the active and sham intervention groups in post-treatment severity of OCD, estimated using an ANCOVA model that adjusts for pre-treatment severity of OCD.

Secondary Outcomes (9)

• response and remission

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up

• Standard Mean Difference (SMD) on the Clinical Global Impression (CGI) severity scale

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up

• Clinical Global Impression (CGI) improvement scale

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up

• Quality of life (EQ-5D-5L)

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up

• Societal costs, measured through the iMTA Productivity Cost Questionnaire (iPCQ)

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 6 and 12 months follow-up

Other Outcomes (1)

• tic severity, measured using the Yale Global Tic Severity Scale (YGTSS)

  baseline (T0) versus directly post-treatment (5, 6 or 7 weeks post-baseline, dependent on duration of treatment) + 3, 6 and 12 months follow-up

Study Arms (2)

real rTMS

EXPERIMENTAL

verum rTMS condition, 1500 continuous 1-Hz pulses to the pre-SMA

Combination Product: repetitive transcranial magnetic stimulation (rTMS)

sham rTMS

SHAM COMPARATOR

sham rTMS condition, 1500 continuous 1-Hz pulses to the pre-SMA

Combination Product: repetitive transcranial magnetic stimulation (rTMS)

Interventions

repetitive transcranial magnetic stimulation (rTMS) COMBINATION_PRODUCT

rTMS (real versus sham) is used as adjuvant to ERP

Also known as: exposure therapy with response prevention (ERP)

real rTMS; sham rTMS

Eligibility Criteria

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

You may qualify if:

• OCD as current primary diagnosis
• Age 18 and older
• Yale-Brown Obsessive-Compulsive Scale (YBOCS) score of 16 or higher.
• Insufficient response to state-of-the art exposure therapy with response prevention (ERP) and/or drop-out from ERP due to extreme anxiety/avoidance
• The following comorbid disorders are allowed (as long as OCD is the current primary diagnosis): depression, other anxiety disorders, ADHD, tic/Tourette's disorder, eating disorders, personality disorders, autism spectrum disorder (when this does not dominate the clinical profile, i.e. is not main diagnosis).
• Commitment to actively undergo intensive exposure therapy (both supervised during ERP sessions, as well as unsupervised at home)
• Unmedicated (for at least 8 weeks) or stable dosage of psychotropic medication (for at least 8 weeks), involving serotonergic antidepressants (SSRI, SNRI, clomipramine). Other psychotropic medication that is allowed (provided dosage is stably established for at least 8 weeks): methylphenidate, mood stabilizers, antipsychotic drugs
• Ability to participate in frequent treatment sessions (4 days/week, for 5 (or 6, or 7) weeks) at one of the 5 sites nearest to their home and/or work
• Ability to participate in pre-treatment MRI session (for neuronavigation) at one of the 3 academic sites nearest to their home and/or work
• Capacity for providing informed consent

You may not qualify if:

• OCD patients with hoarding as main symptom dimension
• The following comorbid disorders (current diagnosis) are not allowed: psychotic disorders, bipolar disorder, autism spectrum disorder (when this dominates the clinical profile, i.e. is diagnosed as main disorder), substance use disorder
• Active suicidal thoughts and intent to act on it
• Chronic use of benzodiazepines is not allowed
• Cochlear implant
• (History of) epilepsy
• Pregnancy
• Extreme claustrophobia or metallic objects in or on the body, preventing from participation in MRI session
• Space-occupying lesion on MRI
• Previous rTMS treatment (for blinding reasons)

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• GGZ inGeest: collaborator
• Radboud University Medical Center: collaborator
• ProPersona: collaborator
• Maastricht University Medical Center: collaborator
• Mondriaan: collaborator
• Neurocare: collaborator

Study Sites (8)

Amsterdam UMC, location VU Medical Center

Amsterdam, North Holland, 1081 HZ, Netherlands

RECRUITING

GGZ inGeest

Amsterdam, Netherlands

RECRUITING

Neurocare

Eindhoven, Netherlands

NOT YET RECRUITING

Neurocare

Groningen, Netherlands

NOT YET RECRUITING

Maastricht UMC+

Maastricht, Netherlands

NOT YET RECRUITING

Mondriaan

Maastricht, Netherlands

NOT YET RECRUITING

ProPersona

Nijmegen, Netherlands

NOT YET RECRUITING

Radboudumc

Nijmegen, Netherlands

NOT YET RECRUITING

Related Publications (4)

• Fitzsimmons SMDD, van der Werf YD, van Campen AD, Arns M, Sack AT, Hoogendoorn AW; other members of the TETRO Consortium; van den Heuvel OA. Repetitive transcranial magnetic stimulation for obsessive-compulsive disorder: A systematic review and pairwise/network meta-analysis. J Affect Disord. 2022 Apr 1;302:302-312. doi: 10.1016/j.jad.2022.01.048. Epub 2022 Jan 15.

  PMID: 35041869 BACKGROUND

• Rehn S, Eslick GD, Brakoulias V. A Meta-Analysis of the Effectiveness of Different Cortical Targets Used in Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Obsessive-Compulsive Disorder (OCD). Psychiatr Q. 2018 Sep;89(3):645-665. doi: 10.1007/s11126-018-9566-7.

  PMID: 29423665 BACKGROUND

• Zhou DD, Wang W, Wang GM, Li DQ, Kuang L. An updated meta-analysis: Short-term therapeutic effects of repeated transcranial magnetic stimulation in treating obsessive-compulsive disorder. J Affect Disord. 2017 Jun;215:187-196. doi: 10.1016/j.jad.2017.03.033. Epub 2017 Mar 18.

  PMID: 28340445 BACKGROUND

• Stein DJ, Costa DLC, Lochner C, Miguel EC, Reddy YCJ, Shavitt RG, van den Heuvel OA, Simpson HB. Obsessive-compulsive disorder. Nat Rev Dis Primers. 2019 Aug 1;5(1):52. doi: 10.1038/s41572-019-0102-3.

  PMID: 31371720 BACKGROUND

MeSH Terms

Interventions

Transcranial Magnetic Stimulation; Implosive Therapy

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Desensitization, Psychologic; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Odile A van den Heuvel, MD PhD

CONTACT

+31-20-4444444; oa.vandenheuvel@amsterdamumc.nl

Tjardo S Postma, MD

CONTACT

+31-20-4444444; tetro@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof.dr. (MD PhD)

Model Details: multi-center placebo-controlled double-blind randomized controlled trial with an intervention phase of 5-7 weeks and a follow-up phase of 12 months

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 18, 2022
• Study Start: May 16, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (8)