Clinical trial NCT05177601: iTBS-DCS in Obsessive Compulsive Disorder
Official title: A Randomized Sham and Placebo-controlled Trial of Adjunctive D-cycloserine in Repetitive Transcranial Magnetic Stimulation for Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2022-01-04
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Yale-Brown Obsessive Compulsive Scale (YBOCs)
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Secondary outcomes:
measure: Clinical Remission
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Clinical Response
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in self reported anxiety symptoms
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in quality of Life as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in self reported depressive symptoms as measured by The Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in self reported measures of workplace productivity
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Clinical Global Impression- Severity
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Clinical Global Impression- Improvement
timeFrame: Administered at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Stool samples- microbiome analysis
timeFrame: Samples will be collected at baseline, after TMS treatment (week 4) and 4 weeks after completion of TMS (week 8)
measure: Stool samples- metabolomics
timeFrame: Samples will be collected at baseline, after TMS treatment (week 4) and 4 weeks after completion of TMS (week 8)
measure: Change in Cognitive Function - THINC-it- PDQ-5
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in Cognitive Function - THINC-it- Choice Reaction Time
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in Cognitive Function - THINC-it- Working Memory
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in Cognitive Function - THINC-it- Digit Symbol Substitution
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in Cognitive Function - THINC-it- Trail Making Test part B
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Implicit Suicidality
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Wisconsin Card Sorting Task (WCST)
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Stop Signal Task
timeFrame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in self reported cognitive failures as measured by The Cognitive Failures Questionnaire (CFQ)
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: VAS for General Health
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in suicidal intentions
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
measure: Change in severity of skin-picking symptoms
timeFrame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Other outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Daily Monday-Friday throughout study (4 weeks)
measure: Side Effects
timeFrame: The TSES will be administered at baseline, and weekly throughout study (Week 1, Week 2, Week 3, Week 4), and at follow up (week 8)
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Alexander McGirr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: