To characterise and compare neurobiological mechanisms underlying behavioural effects of three different rTMS treatment protocols in OCD using multimodal neuroimaging, with a focus on neuroplasticity.
ID
Source
Brief title
Condition
- Psychiatric disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter is change in tbfMRI blood-oxygen level dependent (BOLD)
response following rTMS.
Secondary outcome
Secondary parameter: Changes in clinical outcomes
Exploratory objectives
• To characterise and compare other neurobiological changes following different
rTMS protocols in OCD using multimodal neuroimaging: to include:
- Functional connectivity
- Structural connectivity
- Neurotransmitter concentrations
- Cortical excitation and inhibition
• To characterise and compare cognitive changes following different rTMS
protocols, specifically:
- Planning
- Response inhibition
- Emotion regulation
- Error processing
• To relate changes in neuroimaging measures to changes in clinical/cognitive
measures in order to identify underlying mechanisms
• To identify baseline clinical, cognitive and neuroimaging factors that
predict degree of response to rTMS + ERP treatment.
Background summary
Obsessive-compulsive disorder (OCD) is a common neurodevelopmental disorder
characterised by obsessions (intrusive thoughts) and compulsions (repetitive
behaviours). These symptoms are linked to functional and structural alterations
in fronto-striatal brain circuits. It is possible to induce plastic changes in
brain circuits using repetitive transcranial magnetic stimulation (rTMS), and
previous clinical studies have shown that rTMS relieves OCD symptoms. However,
it is unknown what the optimal stimulation protocol is, and the underlying
neurobiological mechanisms of rTMS in OCD have been incompletely characterised.
Study objective
To characterise and compare neurobiological mechanisms underlying behavioural
effects of three different rTMS treatment protocols in OCD using multimodal
neuroimaging, with a focus on neuroplasticity.
Study design
A three-arm proof-of-concept randomised controlled trial. OCD patients will be
randomised to three treatment groups with pre-post neuroimaging, clinical, and
cognitive measures
Intervention
The three treatment groups will each recieve a different rTMS treatment
protocol. Treatment will be delivered twice a week for 8 weeks (16 sessions
total), combined with in vivo exposure with response prevention psychotherapy
(ERP), plus 3 ERP sessions without rTMS.
Study burden and risks
Participants will attend 4 assessment timepoints (T0-3), and 16 treatment
sessions (S1-16) plus three ERP sessions without TMS (Sx,y,z):
Assessments:
T0: Baseline sessions (on different days):
a. Assessment of inclusion/exclusion criteria (including TMS
suitability/resting motor threshold) + clinical and cognitive assessments (3
hrs)
b. MRI assessments (sMRI, rsfMRI, tbfMRI, DTI, MRS) (2 hrs)
c. TMS/EEG assessments (EEG, TMS-EMG, TMS-EEG) (3hrs)
T1: Mid-treatment:
a. Clinical assessment (10 mins)
b. TMS/EEG assessments (EEG, TMS-EMG, TMS-EEG) (3hr)
T2: Post treatment (on different days):
a. Clinical assessments (10 min);
b. MRI assessments (2 hrs),
c. TMS/EEG assessments (3hrs)
T3: Follow up
a. Clinical assessments (30 mins), b. TMS/EEG assessments (3hr)
S1-16: Treatment sessions: 45 mins rTMS + 45 mins ERP 2x per week for 8 weeks,
plus an introduction session (Sx) and two evaluation sessions (Sy, Sz) of 45
mins each.
Risk to participants is considered to be low.
Benefit: rTMS + ERP therapy is expected to relieve OCD symptoms.
Healthy controls will attend for timepoint T0 only (i.e. only baseline
assessment sessions)
De Boelelaan 1108
Amsterdam 1081 HZ
NL
De Boelelaan 1108
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
OCD patients:
- Age between 18 and 65
- Primary DSM-5 diagnosis of OCD (established by the SCID-I) (comorbid
diagnoses of depression and other anxiety disorders allowed)
- 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 CBT in lifetime (minimum of 8 sessions
completed)
- At least 1 previous attempt with serotonergic medication (SSRI or
clomipramine, minimum 12 weeks (or 3 weeks if stopped due to side effects)) or
strong preference for non-pharmacological treatment
- Capacity to provide informed consent
- Suitability to participate in the trial as assessed by including
clinician, Healthy controls (baseline measurements only):
- Age between 18 and 65
- Capacity to provide informed consent
Exclusion criteria
OCD patients:
- MRI exclusion criteria: pregnancy, iron in the body, metal in the teeth,
claustrophobia, any known neurological diseases (including epilepsy), previous
brain surgery, head trauma that resulted in unconsciousness for at least 1 hour
- TMS exclusion criteria: metallic implanted devices (e.g. pacemakers,
cochlear implants), epilepsy, family history of epilepsy (1st degree family
member), any known neurological disorder that causes a lesion to the brain
(multiple sclerosis, previous serious head trauma, stroke, etc), pregnancy,
breastfeeding, use of pro-convulsive medications or medication affecting
cortical excitability (e.g. anti-epileptics, benzodiazepines, antihistamines),
syncope, severe heart disease, sleep deprivation, comorbid substance
use/abuse/dependence (including alcohol), resting motor threshold >75% of
maximum stimulator output, or no useful MEP elicitable.
- Schizophrenia, bipolar disorder, active suicidal ideation, use of
antipsychotics within last 12 weeks
- previous experience with rTMS as treatment, Healthy controls (baseline
measurements only):
- Current DSM-5 diagnosis (established by the SCID-I)
- Personal history of DSM-5 diagnosis, except for depression or anxiety
disorder longer than 12 months ago
- No use of psychotropic medications within last 12 months
- 1st degree family member with OCD
- MRI exclusion criteria (as above)
- TMS exclusion criteria (as above)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03667807 |
| CCMO | NL67067.029.18 |