Suicidal IdeationPhase 2NCT06121284
iTBS+D-Cycloserine for Youth Suicide
A Phase 2 study testing D-Cycloserine and intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation in people with Suicidal Ideation and Suicide, Attempted, run by University of Calgary at 1 site in Canada.
Trial summary
Background and Rationale: Suicide is the second leading cause of death in Canadian Emerging Adults (EAs; 18-24yrs). Current treatments for suicidal thoughts and behaviors are limited and novel treatments are required to save lives. Read more about this study
- Who is it for?
- Ages 18 to 24 years
- Conditions the study is for
- Suicidal Ideation, Suicide, Attempted, Depression, Anxiety
- What is being tested?
- D-Cycloserine and intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteCanada
- Study dates
- 11 Mar 2024to Sep 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 24 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Individuals aged 18 to 24 years
- Any sex or gender
- Are competent to consent to treatment
- Have previously attempted suicide as defined by the Columbia Suicide Severity Rating Scale
- Currently have suicidal ideation as defined by a score ≥4 on item 10 of the MADRS in the past week. Individuals with active suicidal ideation, defined as suicidal ideation with the intention to act on a plan that might result in death, are only eligible if currently hospitalized
- Moderate depression measured on the 17-item Hamilton Rating Scale for Depression (HAMD-17) ≥15
Show all 9Show fewer
- Are able to adhere to the treatment schedule
- Pass the TMS adult safety screening (TASS) questionnaire
- Have a normal ECG, CBC, electrolytes, BUN, creatinine, eGFR, AST, ALT, and GGT within the last month.
Who cannot join
- Allergy to cycloserine or any excipients due to possible anaphylaxis or other reactions.
- Current alcohol or substance misuse.
- Current symptoms or history of psychosis, as this can be aggravated by D-Cycloserine.
- Are currently pregnant, breast feeding or plan to become pregnant during the study, as the effects of D-Cycloserine on the fetus are unknown. Health Canada requires that women of reproductive potential utilize either highly effective birth control or double barrier method of contraception. Abstinence is only acceptable when it is the usual and preferred lifestyle of the participant.
- Have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
- Have previously failed a course of rTMS treatment
Show all 11Show fewer
- Have any significant neurological disorder or insult as this increased the risk of adverse events with rTMS 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 15 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 because these can heat or move due to the rapidly alternating magnetic field generated by rTMS.
- Are currently being treated with GABA agonists such as benzodiazepines, cyclopyrrolones, gabapentin/pregabalin, or anticonvulsant due to the potential to limit TMS efficacy
- Those with a history of intracranial implants or metal, or with any potential metal fragments in the body (particularly in the orbits).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 1N4
Alexander McGirr, MD PhD, 4032106410, alexander.mcgirr@ucalgary.ca
About this study
Official title: A Randomized Placebo-controlled Trial of Adjunctive D-Cycloserine and Accelerated Intermittent Theta Burst Stimulation for Emerging Adults With Suicidal Ideation
Background and Rationale: Suicide is the second leading cause of death in Canadian Emerging Adults (EAs; 18-24yrs). Current treatments for suicidal thoughts and behaviors are limited and novel treatments are required to save lives. Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulation treatment for major depressive disorder, a mental health condition at high risk for suicide. It is well tolerated and effective. However, in the child and youth population, it does not appear to be superior to sham-TMS. Therefore, strategies for enhancing TMS outcomes are required.
Over time, TMS can change the function of brain regions important in depression to reduce the symptoms of depression, including suicidal ideation. The investigators believe this occurs through a process called 'synaptic plasticity', or the process by which neurons change their connectivity with other neurons in an activity-dependent manner. Using an adjunct to facilitate these changes in the EA population may improve TMS outcomes, including both implicit and explicit measures of suicide risk.
Read more
The investigators\' previous data indicates that, in adults, the effects of a TMS protocol called intermittent theta-burst stimulation (iTBS) can be enhanced by pairing stimulation with a medication called D-Cycloserine. This FDA-approved medication leads to enhanced synaptic plasticity with iTBS. In adults, this combination led to greater improvements in depression symptoms and both implicit and explicit suicide risk. Implicit suicide risk is measured with a computerized test, called the death/suicide implicit association test (Death/Suicide IAT), and explicit suicide risk is defined as suicidal thoughts reported by the individual.
In the current study, we aim to determine whether the effects of iTBS can be augmented with D-Cycloserine to reduce suicide risk in the EA population. Typical courses of iTBS involve daily treatments over 6 weeks, a timeframe that is not acceptable in individuals experiencing suicidal ideation. For this reason, we will build on data indicating that treatment courses can be condensed by delivering multiple treatments in a single day to accelerate symptomatic improvements. Specifically, our data suggests that (1) 4-weeks of daily iTBS+D-Cycloserine significantly improves implicit and explicit suicide risk and (2) a single-dose of D-Cycloserine paired with two iTBS treatments separated by one hour, enhances the physiological effects of iTBS. As such, in this study, participants will receive two treatments per day, separated by an hour, thereby accelerating a typical 4-week course to 2 weeks.
Research Question and Objectives: To conduct a 2-week double-blind placebo-controlled randomized clinical trial where 54 participants will be randomly assigned to one of two groups: 1) accelerated iTBS+D-Cycloserine, and 2) accelerated iTBS+placebo. The primary outcome of the study is performance on the Death/Suicide-IAT, a measure of suicide risk; however, we will also determine whether pairing stimulation with D-Cycloserine enhances the antidepressant effects of iTBS, reduces suicidal ideation in this population, and reduces the likelihood of engaging in suicidal behavior or having suicidal crises over the following six months.
Read the detailed description
Methods: 54 participants between 18-24 years old with clinically significant past week suicidal ideation, defined as a score ≥4 on item 10 of the Montgomery Asberg Depression Rating Scale (MADRS), at least moderate depressive symptoms (≥15 Hamilton Depression Rating Scale-17 [HAMD-17]), and a history of at least one suicide attempt will be recruited. It is important to note that suicidal ideation occurs on a spectrum and that scores on the MADRS item 10 range from 0-6. A score of 4 = "Probably better off dead. Suicidal thoughts are common, and suicide is considered as a possible solution, but without specific plans or intention." A score of 6 = "Explicit plans for suicide when there is an opportunity. Active preparations for suicide." Within this range, an individual may have active or passive suicidal ideation with or without intent or a plan. Individuals with active suicidal ideation, intent, or plan will be eligible to participate in the study if they are currently admitted as an inpatient.
Participants will complete a screening visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized in a 1:1 ratio to receive either accelerated iTBS+placebo or accelerated iTBS+D-Cycloserine. The randomization sequence will be generated with random number generation, a block size of 6, and allocation concealment.
Double-blind assignment and allocation concealment will be maintained by sequential numbering. Patients will be randomly assigned to receive either accelerated iTBS+D-Cycloserine or accelerated iTBS+placebo treatments. Patients without blood work within the past month will have laboratory tests done to rule out hematological, hepatic, and renal disease.
The primary outcome of interest is change in performance on the Death/Suicide-IAT from baseline to treatment end. Performance on this measure and other cognitive tasks will also be assessed at 1-month and 6-month follow-ups.
Clinical outcomes will be quantified using change on the clinician-rated Scale for Suicidal Ideation (SSI) and MADRS and self-reported measures of depression and anxiety. These symptoms will be assessed at baseline, week-1 (halfway), week-2 (end of treatment), one month, and 6-months post-treatment. Change in suicidal behaviors over the 6-months prior and following treatment will also be assessed using the Columbia Suicide Severity Rating Scale (CSSRS) and medical record review.
- Conditions
- Suicidal Ideation, Suicide, Attempted, Depression, Anxiety
- Being tested
- D-Cycloserine, intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation, Placebo oral tablet
- Keywords
- Transcranial Magnetic Stimulation, Emerging Adults, Youth, Suicidal Ideation, Depression, D-Cycloserine, Cognition
- Medical subject headings
- Suicidal Ideation, Suicide, Attempted, Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-CycloserineDrug
Participants will orally ingest a capsule containing a 100mg dose of the antibiotic d-cycloserine daily (Monday-Friday) during 2 weeks of twice daily rTMS treatment (20 sessions) 60-120 minutes prior to the first rTMS treatment of the day.
intermittent Theta-Burst-repetitive Transcranial Magnetic StimulationDevice
Repetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive twice daily treatments (Monday-Friday) over two weeks (20-sessions).
Placebo oral tabletDrug
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 2 weeks of twice-daily rTMS treatment (20 sessions) 60 - 120 minutes prior to the first rTMS treatment of the day.
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Experimental | Participants will orally ingest a standard 100mg dose of D-Cycloserine daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). D-Cycloserine will be ingested 60-120 minutes prior to the first rTMS treatment of the day. Receives: Drug: D-Cycloserine; Device: intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation |
| Placebo | Placebo comparator | Participants will orally ingest a standard 100mg dose of a microcrystalline placebo capsule daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). The Placebo will be ingested 60-120 minutes prior to the first rTMS treatment of the day. Receives: Device: intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation; Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Performance on the Death Implicit Association Test (D-IAT) at treatment end
The D-IAT measures reaction time in categorizing life and death-related words. Different pairings of target attributes (Life/Death) and attribute dimensions (Me/Not Me) create implicit associations between the self with life and death. The D-IAT score is interpreted as a difference in strength of implicit association of the self with life and death. Scores range from -2 (strong implicit association with life) to +2 (strong implicit association with death).
Measured: Change from baseline to end of treatment (week 2)
Secondary outcomes (20)
Performance on the Death Implicit Association Test (D-IAT) at follow up
The D-IAT measures reaction time in categorizing life and death-related words. Different pairings of target attributes (Life/Death) and attribute dimensions (Me/Not Me) create implicit associations between the self with life and death. The D-IAT score is interpreted as a difference in strength of implicit association of the self with life and death. Scores range from -2 (strong implicit association with life) to +2 (strong implicit association with death).
Measured: Baseline, treatment end (2-weeks), 1-month, 6-months
Change on the Scale for Suicidal Ideation (SSI) at end of treatment (week 2)
Change in score on the clinician administered SSI. This consists of 19 items rated on a Likert-scale from 0 to 2. Higher scores are indicative of worse suicidal ideation.
Measured: SSI score from baseline to end of treatment (week 2)
SSI at 1-month post treatment
Score on the clinician-administered SSI. This consists of 19 items rated on a Likert scale from 0 to 2. Higher scores are indicative of worse suicidal ideation.
Measured: SSI score at 1-month post treatment
SSI at 6-months post treatment
Score on the clinician administered SSI. This consists of 19 items rated on a Likert-scale from 0 to 2. Higher scores are indicative of worse suicidal ideation.
Measured: Administered at 6-months post treatment
Change on the Montgomery Asberg Depression Rating Scale (MADRS) post treatment
Change in severity of depressive symptoms as measured by the MADRS, a clinician-rated instrument. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.
Measured: MADRS score at week 2 (post treatment)
Montgomery Asberg Depression Rating Scale (MADRS) at 1-month
Severity of depressive symptoms as measured by the MADRS, a clinician-rated instrument. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.
Measured: MADRS score at 1-month follow up
Montgomery Asberg Depression Rating Scale (MADRS) at 6-months
Severity of depressive symptoms as measured by the MADRS, a clinician-rated instrument. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.
Measured: MADRS score assessed at 6-month follow up
Clinical Global Impression (CGI) - Severity
The CGI-Severity scale is clinician rated from 1-7 representing \'Not at all ill\' to \'Severely ill\'.
Measured: The CGI will be administerd at baseline, week 1, week 2 (end of treatment), 1-month follow up (week 6), and 6-month follow up.
Clinical Global Impression (CGI) - Improvement
The CGI-Severity scale is clinician rated from 1-7 representing \'Not at all ill\' to \'Severely ill\'.
Measured: The CGI will be administerd at baseline, week 1, week 2 (end of treatment), 1-month follow up (week 6), and 6-month follow up.
Change on the Borderline Symptom List-23 (BSL-23)
The BSL is a self-report measure of 23 questions assessing symptoms of borderline personality disorder on a Likert scale from 0-4.
Measured: The BSL-23 will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up visits
Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR)
The Quick Inventory of Depressive Symptomatology (QIDS) rates depression symptoms via self-assessment.Severity of depression can be judged based on the total score.
1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression
Measured: The QIDS-SR will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Generalized Anxiety Disorder-7 item questionnaire (GAD-7)
Anxiety symptoms will be assessed using the 7 item Generalized Anxiety Disorder (GAD-7) questionnaire. The GAD-7 measures self-reported feelings of anxiety within the last 2 weeks. Scores range from 0-21. Scores of 5, 10, and 15 represent cut points for mild, moderate, and severe anxiety, respectively.
Measured: The GAD-7 will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Difficulties in Emotional Regulation Scale (DERS)
The DERS is a 36-item self-reported measure of emotional regulation ability, rated on a Likert-Scale from 0 (almost never) to 5 (almost always).
Measured: The DERS will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
WHO Quality of Life Questionnaire (WHOQOL-BREF)
The WHOQOL-BREF is a self-reported questionnaire which assesses individual\'s perception of their quality of life across 4 domains; physical health, psychological, social relationships and environment. Domains scores are calculated to range from 0-20 and scaled in a positive direction (ie. higher scores denote higher quality of life).
Measured: The WHOQOL-BREF will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Beck Hopelessness Scale (BHS)
The BHS is a self-reported measure of hopelessness that includes 20 true/false questions that assess three different aspects of hopelessness: feelings about the future, loss of motivation, and future expectations. Higher scores reflect higher levels of hopelessness.
Measured: The BHS will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Performance on the Spatial Working Memory Task (SWM; CANTAB)
The SWM task requires the retention and manipulation of visuo-spatial information. It acts as a measure of strategy and errors when using spatial working memory.
Measured: the SWM task will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up
Performance on the Stroop Word-Colour Task (SWCT)
The SWCT is a measure of cognitive control which uses reaction times to assess an individual\'s ability to inhibit a pre-potent response.
Measured: The SWCT will be completed at baseline, week 2 (end of treatment), 1-month and 6-month follow up
Performance on the Intra-Extra Dimensional Set Shift (IED; CANTAB)
The IED measures an individual\'s ability to understand and apply the rules of a game as the rules change (acquisition and reversal).
Measured: The IED will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up
Suicidal behaviors over 6-months post-treatment
Suicide attempts, aborted suicide attempts, interrupted suicide attempts, suicidal ideation and non-suicidal self-injury will be measured using the Columbia Suicide Severity Rating Scale (CSSRS). Higher scores on the CSSRS are indicative of more severe suicidal behaviors.
Measured: Columbia Suicide Severity Rating Scale and electronic medical record verification assessed 6-months post treatment
Change in psychiatric emergency department visits and hospitalizations over 6 months pre and post-treatment
Participants\' medical record will be reviewed for emergency department presentations for a psychiatric chief complaint and psychiatric hospitalizations in the six months prior to and following treatment.
Measured: The medical record will be accessed six months after the completion of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start11 Mar 2024
- Primary completionJul 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alberta
- Responsible party
- Sponsor
- Investigators
- Alexander McGirr, MD PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06121284
- Sponsor's protocol ID
- REB22-1115
- Status last verified
- Nov 2024
- First submitted
- 25 Aug 2023
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-controlled Trial of Adjunctive D-Cycloserine and Accelerated Intermittent Theta Burst Stimulation for Emerging Adults With Suicidal Ideation
- ClinicalTrials.gov ID
- NCT06121284
- Acronym / sponsor ID
- REB22-1115
- Conditions
- Suicidal Ideation, Suicide, Attempted, Depression, Anxiety
- Keywords
- Transcranial Magnetic Stimulation, Emerging Adults, Youth, Suicidal Ideation, Depression, D-Cycloserine, Cognition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- University of Alberta
- Study start
- 11 Mar 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 7 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background and Rationale: Suicide is the second leading cause of death in Canadian Emerging Adults (EAs; 18-24yrs). Current treatments for suicidal thoughts and behaviors are limited and novel treatments are required to save lives. Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulation treatment for major depressive disorder, a mental health condition at high risk for suicide. It is well tolerated and effective. However, in the child and youth population, it does not appear to be superior to sham-TMS. Therefore, strategies for enhancing TMS outcomes are required.
Over time, TMS can change the function of brain regions important in depression to reduce the symptoms of depression, including suicidal ideation. The investigators believe this occurs through a process called 'synaptic plasticity', or the process by which neurons change their connectivity with other neurons in an activity-dependent manner. Using an adjunct to facilitate these changes in the EA population may improve TMS outcomes, including both implicit and explicit measures of suicide risk.
The investigators\' previous data indicates that, in adults, the effects of a TMS protocol called intermittent theta-burst stimulation (iTBS) can be enhanced by pairing stimulation with a medication called D-Cycloserine. This FDA-approved medication leads to enhanced synaptic plasticity with iTBS. In adults, this combination led to greater improvements in depression symptoms and both implicit and explicit suicide risk. Implicit suicide risk is measured with a computerized test, called the death/suicide implicit association test (Death/Suicide IAT), and explicit suicide risk is defined as suicidal thoughts reported by the individual.
In the current study, we aim to determine whether the effects of iTBS can be augmented with D-Cycloserine to reduce suicide risk in the EA population. Typical courses of iTBS involve daily treatments over 6 weeks, a timeframe that is not acceptable in individuals experiencing suicidal ideation. For this reason, we will build on data indicating that treatment courses can be condensed by delivering multiple treatments in a single day to accelerate symptomatic improvements. Specifically, our data suggests that (1) 4-weeks of daily iTBS+D-Cycloserine significantly improves implicit and explicit suicide risk and (2) a single-dose of D-Cycloserine paired with two iTBS treatments separated by one hour, enhances the physiological effects of iTBS. As such, in this study, participants will receive two treatments per day, separated by an hour, thereby accelerating a typical 4-week course to 2 weeks.
Research Question and Objectives: To conduct a 2-week double-blind placebo-controlled randomized clinical trial where 54 participants will be randomly assigned to one of two groups: 1) accelerated iTBS+D-Cycloserine, and 2) accelerated iTBS+placebo. The primary outcome of the study is performance on the Death/Suicide-IAT, a measure of suicide risk; however, we will also determine whether pairing stimulation with D-Cycloserine enhances the antidepressant effects of iTBS, reduces suicidal ideation in this population, and reduces the likelihood of engaging in suicidal behavior or having suicidal crises over the following six months.
Detailed description
Methods: 54 participants between 18-24 years old with clinically significant past week suicidal ideation, defined as a score ≥4 on item 10 of the Montgomery Asberg Depression Rating Scale (MADRS), at least moderate depressive symptoms (≥15 Hamilton Depression Rating Scale-17 [HAMD-17]), and a history of at least one suicide attempt will be recruited. It is important to note that suicidal ideation occurs on a spectrum and that scores on the MADRS item 10 range from 0-6. A score of 4 = "Probably better off dead. Suicidal thoughts are common, and suicide is considered as a possible solution, but without specific plans or intention." A score of 6 = "Explicit plans for suicide when there is an opportunity. Active preparations for suicide." Within this range, an individual may have active or passive suicidal ideation with or without intent or a plan. Individuals with active suicidal ideation, intent, or plan will be eligible to participate in the study if they are currently admitted as an inpatient.
Participants will complete a screening visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized in a 1:1 ratio to receive either accelerated iTBS+placebo or accelerated iTBS+D-Cycloserine. The randomization sequence will be generated with random number generation, a block size of 6, and allocation concealment.
Double-blind assignment and allocation concealment will be maintained by sequential numbering. Patients will be randomly assigned to receive either accelerated iTBS+D-Cycloserine or accelerated iTBS+placebo treatments. Patients without blood work within the past month will have laboratory tests done to rule out hematological, hepatic, and renal disease.
The primary outcome of interest is change in performance on the Death/Suicide-IAT from baseline to treatment end. Performance on this measure and other cognitive tasks will also be assessed at 1-month and 6-month follow-ups.
Clinical outcomes will be quantified using change on the clinician-rated Scale for Suicidal Ideation (SSI) and MADRS and self-reported measures of depression and anxiety. These symptoms will be assessed at baseline, week-1 (halfway), week-2 (end of treatment), one month, and 6-months post-treatment. Change in suicidal behaviors over the 6-months prior and following treatment will also be assessed using the Columbia Suicide Severity Rating Scale (CSSRS) and medical record review.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Experimental | Drug: D-Cycloserine, Device: intermittent Theta-Burst-repetitive Transcranial Magnetic StimulationParticipants will orally ingest a standard 100mg dose of D-Cycloserine daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). D-Cycloserine will be ingested 60-120 minutes prior to the first rTMS treatment of the day. |
| Placebo | Placebo comparator | Device: intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation, Drug: Placebo oral tabletParticipants will orally ingest a standard 100mg dose of a microcrystalline placebo capsule daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). The Placebo will be ingested 60-120 minutes prior to the first rTMS treatment of the day. |
Who may qualify
- Ages
- 18 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Individuals aged 18 to 24 years
- Any sex or gender
- Are competent to consent to treatment
- Have previously attempted suicide as defined by the Columbia Suicide Severity Rating Scale
- Currently have suicidal ideation as defined by a score ≥4 on item 10 of the MADRS in the past week. Individuals with active suicidal ideation, defined as suicidal ideation with the intention to act on a plan that might result in death, are only eligible if currently hospitalized
Key exclusion criteria (11 listed)
- Allergy to cycloserine or any excipients due to possible anaphylaxis or other reactions.
- Current alcohol or substance misuse.
- Current symptoms or history of psychosis, as this can be aggravated by D-Cycloserine.
- Are currently pregnant, breast feeding or plan to become pregnant during the study, as the effects of D-Cycloserine on the fetus are unknown. Health Canada requires that women of reproductive potential utilize either highly effective birth control or double barrier method of contraception. Abstinence is only acceptable when it is the usual and preferred lifestyle of the participant.
- Have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-CycloserineParticipants will orally ingest a capsule containing a 100mg dose of the antibiotic d-cycloserine daily (Monday-Friday) during 2 weeks of twice daily rTMS treatment (20 sessions) 60-120 minutes prior to the first rTMS treatment of the day. | Drug | D-Cycloserine |
| intermittent Theta-Burst-repetitive Transcranial Magnetic StimulationRepetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive twice daily treatments (Monday-Friday) over two weeks (20-sessions). | Device | D-Cycloserine, Placebo |
| Placebo oral tabletParticipants 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 2 weeks of twice-daily rTMS treatment (20 sessions) 60 - 120 minutes prior to the first rTMS treatment of the day. | Drug | Placebo |
Primary outcome
Performance on the Death Implicit Association Test (D-IAT) at treatment end
Time frame: Change from baseline to end of treatment (week 2)
The D-IAT measures reaction time in categorizing life and death-related words. Different pairings of target attributes (Life/Death) and attribute dimensions (Me/Not Me) create implicit associations between the self with life and death. The D-IAT score is interpreted as a difference in strength of implicit association of the self with life and death. Scores range from -2 (strong implicit association with life) to +2 (strong implicit association with death).
20 secondary outcomes
Performance on the Death Implicit Association Test (D-IAT) at follow up
Time frame: Baseline, treatment end (2-weeks), 1-month, 6-months
Change on the Scale for Suicidal Ideation (SSI) at end of treatment (week 2)
Time frame: SSI score from baseline to end of treatment (week 2)
SSI at 1-month post treatment
Time frame: SSI score at 1-month post treatment
SSI at 6-months post treatment
Time frame: Administered at 6-months post treatment
Change on the Montgomery Asberg Depression Rating Scale (MADRS) post treatment
Time frame: MADRS score at week 2 (post treatment)
Montgomery Asberg Depression Rating Scale (MADRS) at 1-month
Time frame: MADRS score at 1-month follow up
Montgomery Asberg Depression Rating Scale (MADRS) at 6-months
Time frame: MADRS score assessed at 6-month follow up
Clinical Global Impression (CGI) - Severity
Time frame: The CGI will be administerd at baseline, week 1, week 2 (end of treatment), 1-month follow up (week 6), and 6-month follow up.
Clinical Global Impression (CGI) - Improvement
Time frame: The CGI will be administerd at baseline, week 1, week 2 (end of treatment), 1-month follow up (week 6), and 6-month follow up.
Change on the Borderline Symptom List-23 (BSL-23)
Time frame: The BSL-23 will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up visits
Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR)
Time frame: The QIDS-SR will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Generalized Anxiety Disorder-7 item questionnaire (GAD-7)
Time frame: The GAD-7 will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Difficulties in Emotional Regulation Scale (DERS)
Time frame: The DERS will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
WHO Quality of Life Questionnaire (WHOQOL-BREF)
Time frame: The WHOQOL-BREF will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Beck Hopelessness Scale (BHS)
Time frame: The BHS will be completed at baseline, week 2, 1-month, and 6-month follow up visits.
Performance on the Spatial Working Memory Task (SWM; CANTAB)
Time frame: the SWM task will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up
Performance on the Stroop Word-Colour Task (SWCT)
Time frame: The SWCT will be completed at baseline, week 2 (end of treatment), 1-month and 6-month follow up
Performance on the Intra-Extra Dimensional Set Shift (IED; CANTAB)
Time frame: The IED will be completed at baseline, week 2 (end of treatment), 1-month, and 6-month follow up
Suicidal behaviors over 6-months post-treatment
Time frame: Columbia Suicide Severity Rating Scale and electronic medical record verification assessed 6-months post treatment
Change in psychiatric emergency department visits and hospitalizations over 6 months pre and post-treatment
Time frame: The medical record will be accessed six months after the completion of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander McGirr, MD PhD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing D-Cycloserine and intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation in people with Suicidal Ideation and Suicide, Attempted, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexander McGirr, MD PhD (403 210 6410, alexander.mcgirr@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Performance on the Death Implicit Association Test (D-IAT) at treatment end (time frame: Change from baseline to end of treatment (week 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.