iTBS-DCS in Obsessive Compulsive Disorder

NCT05177601 | Unknown Phase 2 FDA Drug FDA Device

• 1 other identifier: REB21-0265
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder

Outcome Measures

Primary Outcomes (1)

• Yale-Brown Obsessive Compulsive Scale (YBOCs)

  Change in severity of Obsessive Compulsive Disorder (OCD) symptoms as measured by the YBOCS, a clinician-rated instrument. Scores on the YBOCS range from 0 (no Symptoms) to 40 (Extreme Symptoms). Ranges of severity are: 0-7 Subclinical range, 8-15 Mild, 16-23 Moderate, 24-31 Severe, and 32-40 Extreme.

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Secondary Outcomes (23)

• Clinical Remission

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

• Clinical Response

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

• Change in self reported anxiety symptoms

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

• Change in quality of Life as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire

  Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Other Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  Daily Monday-Friday throughout study (4 weeks)

• Side Effects

  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)

Study Arms (4)

TMS+DCS

ACTIVE COMPARATOR

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.

Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS); Drug: D-cycloserine

TMS+Placebo

ACTIVE COMPARATOR

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.

Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS); Drug: Placebo oral capsule

shamTMS+DCS

SHAM COMPARATOR

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.

Device: Sham rTMS; Drug: D-cycloserine

shamTMS+placebo

PLACEBO COMPARATOR

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.

Device: Sham rTMS; Drug: Placebo oral capsule

Interventions

iTBS repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

rTMS is a non-invasive procedure in which cerebral electrical activity is influenced by a rapidly changing magnetic field. The magnetic field is created by a plastic-encased coil which is placed over the patient's scalp. The magnetic field can be directed onto specific areas of the brain. rTMS can modulate cerebral activity by low or high frequencies. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of mood disorders.

Also known as: MAGPRO X100 stimulator

TMS+DCS; TMS+Placebo

Sham rTMS DEVICE

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Also known as: MAGPRO X100 stimulator

shamTMS+DCS; shamTMS+placebo

D-cycloserine DRUG

Daily oral D-cycloserine 100mg during TMS treatments (20 days).

Also known as: Seromycin

TMS+DCS; shamTMS+DCS

Placebo oral capsule DRUG

Daily oral placebo during the TMS treatments (20 days).

TMS+Placebo; shamTMS+placebo

Eligibility Criteria

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

You may qualify if:

• Males and females aged 18 to 65 years
• are competent to consent to treatment
• have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of DSM-5 criteria Obsessive Compulsive Disorder.
• 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.
• have a score ≥ 20 on the YBOCS.
• have had no change in dose, or initiation of any psychotropic medication in the 8 weeks prior to randomization
• are able to adhere to the treatment schedule
• pass the TMS adult safety screening (TASS) questionnaire

You may not qualify if:

• Allergy to cycloserine.
• have an alcohol or substance use disorder within the last 3 months
• have suicidal ideation (score of 4 ≥ on item 10 of MADRS)
• are at a significant risk of harm to themselves or others
• Current symptoms of psychosis
• History of psychosis
• are currently pregnant , breast feeding or plan to become pregnant
• 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.
• history of non-response to rTMS treatment.
• 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
• have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
• 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
• 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
• are currently (or in the last 4 weeks) taking lorazepam or any other benzodiazepine due to the potential to limit rTMS efficacy

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Alexander McGirr, MD, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: January 4, 2022
• Study Start: November 26, 2021
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2025
• Last Updated: September 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)