TMS-induced Plasticity Improving Cognitive Control in OCD (TIPICCO)

Transcranial Magnetic Stimulation (TMS)-Induced Plasticity Improving Cognitive Control in Obsessive-compulsive Disorder (OCD)

Repetitive transcranial magnetic stimulation (rTMS) has been shown in several previous clinical trials to be an effective treatment for obsessive-compulsive disorder (OCD). However, the neural working mechanisms of rTMS in OCD are unknown, and the optimal stimulation sites have not yet been established. Our study aims to compare the clinical and neurobiological effects of three different rTMS stimulation protocols in OCD patients. 8 weeks of rTMS therapy will be delivered in combination with cognitive behavioural therapy. Multimodal neuroimaging will be carried out before and after treatment in order to demonstrate the neurobiological effects of the therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HZ
      • Amsterdam UMC, location VU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

OCD patients:

• Age between 18 and 65
• Primary DSM-5 diagnosis of OCD
• Moderate to severe OCD symptoms (expressed as a minimum score of 16 on the Yale - Brown Obsessive Compulsive Scale (YBOCS)
• Unmedicated or stable dose of medication for at least 12 weeks prior to randomisation - with no plans to change dose during the study period
• At least 1 previous attempt at cognitive behavioural therapy (CBT) in lifetime
• At least 1 previous attempt with serotonergic medication or strong preference for non-pharmacological treatment
• Capacity to provide informed consent

Healthy controls (baseline measurements only):

• Age between 18 and 65
• Capacity to provide informed consent

Exclusion Criteria:

OCD patients:

• MRI exclusion criteria (metal in body, pregnancy)
• TMS exclusion criteria (metal in body, history of epilepsy)
• Schizophrenia, bipolar disorder, active suicidal ideation, use of antipsychotics within last 12 weeks
• previous experience with rTMS as treatment

Healthy controls:

• Current Diagnostic and Statistical Manual (DSM)-5 diagnosis
• Personal history of DSM-5 diagnosis
• use of psychotropic medications within last 12 months
• 1st degree family member with OCD
• MRI exclusion criteria (as above)
• TMS exclusion criteria (as above)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS condition 1	Device: Repetitive transcranial magnetic stimulation; Non invasive brain stimulation; Other Names: rTMS, TMS
Experimental: rTMS condition 2	Device: Repetitive transcranial magnetic stimulation; Non invasive brain stimulation; Other Names: rTMS, TMS
Experimental: rTMS condition 3	Device: Repetitive transcranial magnetic stimulation; Non invasive brain stimulation; Other Names: rTMS, TMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
task based functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) response	Change in task based fMRI BOLD response following rTMS	Baseline and 12 weeks (i.e. post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	OCD symptom severity	Baseline, 6 weeks, (i.e. during treatment), 12 weeks (i.e. post-treatment), 22 weeks (i.e. follow-up)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional connectivity	Measured using resting state fMRI	Baseline and 12 weeks (i.e. post-treatment)
Structural connectivity	Measured using diffusion tensor imaging (DTI) MRI	Baseline and 12 weeks (i.e. post-treatment)
Cortical excitation and inhibition (Motor-evoked potential amplitude, TMS-evoked potential, short interval cortical inhibition, long interval cortical inhibition)	Measured using single and double pulse TMS + electromyography (EMG) / electroencephalography (EEG)	Baseline, 6 weeks, (i.e. during treatment), 12 weeks (i.e. post-treatment), 22 weeks (i.e. follow-up)
Neurotransmitter concentrations	Measured using magnetic resonance spectroscopy (MRS)	Baseline and 12 weeks (i.e. post-treatment)
Planning	Measured using Tower of London cognitive task	Baseline, 12 weeks (i.e. post-treatment)
Response inhibition	Measured using the stop-signal cognitive task	Baseline, 12 weeks (i.e. post-treatment)
Error processing	Measured using the Flanker cognitive task	Baseline, 6 weeks, (i.e. during treatment), 12 weeks (i.e. post-treatment), 22 weeks (i.e. follow-up)
EEG measures	Resting state EEG, EEG event related potentials measured during tasks (Error related negativity using Flanker task, Late Positive Potential during appraisal of emotional stimuli)	Baseline, 6 weeks, (i.e. during treatment), 12 weeks (i.e. post-treatment), 22 weeks (i.e. follow-up)

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): October 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 91717306

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No