iTBS-DCS in Obsessive Compulsive Disorder

University of Calgary

Status and phase: Active, not recruiting; Phase 2

Conditions: Obsessive-Compulsive Disorder

Treatments: Drug: D-cycloserine; Drug: Placebo oral capsule; Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham rTMS

Study type: Interventional

Funder types: Other

Identifiers

NCT05177601

REB21-0265

Details and patient eligibility

About

Obsessive Compulsive Disorder (OCD)is a common and debilitating illness. For an unacceptable proportion of patients, depressive symptoms remain impairing despite multiple treatments.

In August 2018, the FDA approved transcranial magnetic stimulation (TMS) for the treatment of OCD based on a large study demonstrating efficacy. Our neurophysiological data and clinical data in depression suggests that we can enhance the effects of TMS by using an adjunctive medication called D-Cyloserine (DCS, 100mg) in conjunction with stimulation. The mechanism by which this is achieved is called synaptic plasticity, or the activity dependent changes that occur with brain stimulation.

Research Question and Objectives: To conduct a randomized sham- and placebo-controlled trial of DCS in adjunct with rTMS in OCD. Participants will be randomized to receive 100mg of DCS or placebo together with TMS.

Full description

Methods: Eighty one patients (males and females aged 18-65, with a score ≥20 on the Yale-Brown Obsessive Compulsive Scale, stable selective serotonin reuptake inhibitors or cognitive behavioral therapy for 2 months) will be recruited. Patients will be randomized 2:2:1:1 TMS+DCS, TMS+Placebo, Sham+DCS or Sham+Placebo. Participants who do not have recent bloodwork will have laboratory tests to rule out haematological, hepatic, and renal disease, and participants will be screened for suicidal ideation. The dose of DCS will be 100mg, taken daily for four weeks. Clinical outcomes will be quantified using the Yale-Brown Obsessive Compulsive Scale, a gold standard clinician rated instrument for OCD, as well as measures of depression and anxiety. Participants will complete a short battery of cognitive tests and questionnaires to measure self-reported symptoms of depression, anxiety and quality of life. Fecal samples will be taken at baseline, week 4 and week 8 to characterize any changes in the microbiome. Participants clinical symptoms will be evaluated again one-month after treatment. At this time, all participants who received sham-rTMS will be offered an additional 4 weeks of open label rTMS.

Enrollment: 81 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males and females aged 18 to 65 years
2. are competent to consent to treatment
3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of DSM-5 criteria Obsessive Compulsive Disorder.
4. have failed to achieve a clinical response to one adequate trial of serotonin reuptake inhibitor or cognitive behavioral therapy with an adequate trial of 2 months medication within the current episode, or been unable to tolerate antidepressant medications.
5. have a score ≥ 20 on the YBOCS.
6. have had no change in dose, or initiation of any psychotropic medication in the 8 weeks prior to randomization
7. are able to adhere to the treatment schedule
8. pass the TMS adult safety screening (TASS) questionnaire

Exclusion criteria

1. Allergy to cycloserine.
2. have an alcohol or substance use disorder within the last 3 months
3. have suicidal ideation (score of 4 ≥ on item 10 of MADRS)
4. are at a significant risk of harm to themselves or others
5. Current symptoms of psychosis
6. History of psychosis
7. are currently pregnant , breast feeding or plan to become pregnant
8. have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of other primary psychiatric diagnoses as assessed by a study investigator to be primary and causing greater impairment than Major Depressive Disorder.
9. have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
10. history of non-response to rTMS treatment.
11. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes
12. have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
13. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
14. If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
15. are currently (or in the last 4 weeks) taking lorazepam or any other benzodiazepine due to the potential to limit rTMS efficacy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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81 participants in 4 patient groups, including a placebo group

TMS+DCS

Active Comparator group

Description:

The Transcranial Magnetic Stimulation (TMS) involves magnetic stimulation of the brain to the left medial prefrontal cortex (mPFC) daily for four weeks. The stimulation is intermittent Theta-Burst (iTBS). Participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine (DCS) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Treatment:

Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

Drug: D-cycloserine

TMS+Placebo

Active Comparator group

Description:

The Transcranial Magnetic Stimulation (TMS) involves magnetic stimulation of the brain to the left medial prefrontal cortex (mPFC) daily for four weeks. The stimulation is intermittent Theta-Burst (iTBS). Participants will orally ingest a capsule identical to that containing the study medication, however this capsule will contain a placebo. They will ingest this capsule daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Treatment:

Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

Drug: Placebo oral capsule

shamTMS+DCS

Sham Comparator group

Description:

Sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered to the brain. Participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine (DCS) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Treatment:

Device: Sham rTMS

Drug: D-cycloserine

shamTMS+placebo

Placebo Comparator group

Description:

Sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered to the brain. Participants will orally ingest a capsule identical to that containing the study medication, however this capsule will contain a placebo. They will ingest this capsule daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Treatment:

Device: Sham rTMS

Drug: Placebo oral capsule