Major Depressive DisorderPhase 1NCT05731323
D-Cycloserine+iTBS PK Study
A Phase 1 study testing D-cycloserine and Transcranial Magnetic Stimulator in people with Major Depressive Disorder, run by University of Calgary at 1 site in Canada.
Trial summary
Background \& Rationale: Major Depressive Disorder (MDD) is a common and debilitating illness that that commonly does not respond to conventional treatments. Transcranial magnetic stimulation (TMS) and intermittent theta-burst stimulation (iTBS) are non-invasive neurostimulation treatments for depression that are… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- D-cycloserine and Transcranial Magnetic Stimulator
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 12 Oct 2022to 22 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged 18 to 65 years
- are competent to consent to treatment
- have a confirmed diagnosis of DSM-5 criteria Major Depressive Disorder with a current episode of at least moderate severity of depression, single or recurrent
- have failed to achieve a clinical response to one adequate trial of antidepressant medication within the current episode, or been unable to tolerate antidepressant medications.
- have current episode of at least moderate severity of depression, as defined by a score ≥ 18 on the HAMD-17 item
- have had no change in dose, or initiation of any psychotropic medication in the 4 weeks prior to randomization
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- are able to adhere to the treatment schedule
- pass the TMS adult safety screening (TASS) questionnaire
- have had blood work (complete blood count, electrolytes, BUN, creatinine, eGFR, AST, ALT and GGT, and ECG) within the reference range. Female participants must have a negative pregnancy test.
Who cannot join
- Allergy to cycloserine.
- have failed adequate trials of ≥4 antidepressant treatments in the current episode.
- 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
Show all 18Show fewer
- history of psychosis
- are currently pregnant, breast feeding or plan to become pregnant over the duration of the study
- have a diagnosis of other primary psychiatric diagnoses as assessed by a study investigator to be primary and causing greater impairment than Major Depressive Disorder.
- have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
- history of non-response to TMS 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 any benzodiazepine, cyclopyrrolone, gabapentin/pregabalin or anticonvulsant due to the potential to limit TMS efficacy
- have an exclusion criteria for MRI: Those with a history of cranial, thoracic or abdominal surgery, with pacemakers, artificial joints or other metallic implants will be excluded from the MRI scan. Subjects that have agreed to participate in the MRI portion of the study will be pre-screened for any potential metal fragments in the body (particularly in the orbits) if they have had any history of doing metal work or have been involved in use/deployment of ammunitions/explosives, welding, piping etc).
- are being currently treated with ethionamide or isoniazid (contraindicated with D-cycloserine)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pharmacokinetic Study of Adjunctive D-cycloserine to Intermittent Theta Burst Stimulation in Major Depressive Disorder
Background \& Rationale: Major Depressive Disorder (MDD) is a common and debilitating illness that that commonly does not respond to conventional treatments. Transcranial magnetic stimulation (TMS) and intermittent theta-burst stimulation (iTBS) are non-invasive neurostimulation treatments for depression that are Health Canada approved. These work by generating magnetic fields outside of the body to change the activity of brain cells to change how the brain works. They have a very favorable profile, with many patients experiencing improvement with minimal side effects.
The investigators recently completed a study pairing iTBS with an FDA approved medication that was chosen because it might enhance iTBS improvements. This medication is called D-cycloserine, an old antibiotic that is rarely used in modern times. Years after it stopped being useful as an antibiotic, scientists recognized other properties that the molecule has, and it is some of these that make it interesting to pair with iTBS. When the investigators did so, they found that compared to iTBS with a placebo, participants who received iTBS+D-cycloserine were more likely to benefit from treatment.
Read more
In this original study, all participants received a fixed dose of 100mg daily. This means that people of very different sizes could have had different drug levels, and the investigators do not know how that impacted outcomes. With this study, there will be no placebo condition because the purpose is to understand whether dosing according to weight matters.
Research Question and Objectives: To describe the pharmacokinetic profile of 100mg oral D-cycloserine and weight-based oral D-cycloserine dosed 25mg/17.5kg among individuals with depression undergoing non-invasive intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) in Major Depressive Disorder.
Read the detailed description
Methods: An open-label study of D-cycloserine (DCS) pharmacokinetics will be performed in patients undergoing iTBS to the left DLPFC as a treatment for Major Depressive Disorder. Twelve patients (males and females aged 18-65, with a score ≥18 on the Hamilton Rating Scale for Depression-17 items, and stable pharmacological and psychological regimens) with an acute Major Depressive Episode will be recruited. Bloodwork and an echocardiogram will be obtained prior to the initiation of the study, and enrollment in the study will be contingent on normal lab results.
Prior to initiating iTBS treatment, participants will receive one oral dose of 100mg DCS. A pharmacokinetic curve will be generated from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs.
Participants will receive iTBS daily for 4 weeks (20 sessions). All participants will be provided with weight-based dosing of DCS to take 120 minutes prior to each iTBS session. Serum levels of weight-based DCS dosing will be measured by blood draws at several time points throughout iTBS treatment. Specifically, a pharmacokinetic curve will be generated on Day 1 of iTBS treatment from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs. Additional time points will be obtained prior to and 120 minutes after the fifth dose (Day 5 of TMS) and prior to and 120 minutes after the sixth dose (Day 6 of TMS, corresponding to the beginning of the second week of TMS).
Antidepressant effects will be quantified using the Montgomery Asberg Depression Rating Scale, a gold standard clinician rated instrument. Participants will complete a short battery of cognitive tests at the beginning and end of the study. Blood work and echocardiogram will be repeated after 4 weeks to confirm safety of low-dose DCS.
Participants will return to the lab for a follow-up assessment 4 weeks after they have finished the TMS protocol (week 8).
- Conditions
- Major Depressive Disorder
- Being tested
- D-cycloserine, Transcranial Magnetic Stimulator
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Also called Seromycin
Daily oral D-cycloserine dosed 25mg/17.5kg body weight during TMS treatment days (20 days).
Transcranial Magnetic StimulatorDevice
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 daily treatments (Monday-Friday) over four weeks.
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Experimental | Prior to initiating TMS therapy, participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine.
During TMS therapy, participants will orally ingest a capsule containing a weight-based dose of the antibiotic d-cycloserine (dosed 25mg/17.5kg body weight) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions). Receives: Drug: D-cycloserine; Device: Transcranial Magnetic Stimulator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
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: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Individual differences in D-cycloserine serum concentration will be correlated with clinical outcomes
Examine whether differential change in clinical outcomes will be mediated by D-Cycloserine plasma levels following weight-based dosing. Participants will provide 10 blood samples to characterize plasma levels of D-Cycloserine following a weight-based dose. The primary efficacy measures will be examined in relation to drug blood levels.
Measured: 10 blood samples: PK curve over the first 2 days of TMS treatment (6 draws) and prior to ingestion and after 120 minutes on day 5 and day 6
Individual fidelity to the protocol will be correlated with differential change in primary outcomes
All participants will be instructed to take the blinded capsule 90 - 120 minutes prior to TMS treatment, ensuring adequate time for drug absorption. Daily logs will be kept by the study staff to confirm time of capsule ingestion and TMS treatment. Any TMS sessions missed, capsule doses missed and/or capsule doses taken at the incorrect time will be tracked. The primary efficacy measures will be examined in relation to adherence to the protocol (20/20 TMS session completed with oral capsule taken between 90 - 120 minutes prior).
Measured: Daily Monday-Friday throughout study (4 weeks)
The variance in D-cycloserine level will be greater in the 100mg dosing condition than in the weight-based dosing condition.
The maximum serum concentration of D-cycloserine in blood serum will be measured by taking blood samples at various timepoints following oral D-cycloserine. Maximum serum concentration following 100mg oral D-cycloserine and weight-based oral D-cycloserine (dosed 25mg/17.5kg) will be compared. Blood samples will be drawn at baseline (pre-ingestion), +30 minutes, +60 minutes, +90 minutes and +24hours after a uniform dosing of 100mg of D-cycloserine and after a weight-based dosing of 25mg D-cycloserine per 17.5kg of body weight.
Measured: PK curve done at baseline (fixed dose) and Day 1 of TMS (weight-based dose). Samples at pre-ingestion, +30 minutes, +60 minutes, +90 minutes, +120 minutes, and +24hours.
Determine whether blood serum levels of D-cycloserine achieved by weight-based dosing is consistent across time.
Serum concentrations of weight-based oral D-cycloserine (dosed 25mg/17.5kg body weight) will be described by collecting blood samples 120 minutes after ingestion of the first, fifth and sixth dose.
Measured: Day 1 of TMS, Day 5 of TMS, and Day 6 of TMS.
Secondary outcomes (14)
Number of participants that achieve clinical remission of depression
Clinical remission of depressive symptoms will be measured by the Montgomery-Asberg Depression Rating Scale (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. A score of </= 10 on the MADRS indicates clinical remission.
Measured: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Number of participants that achieve clinical response (>=50% improvement in depression)
Clinical depression response will be measured by the Montgomery-Asberg Depression Rating Scale (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. A reduction of >/= 50% in the MADRS score indicates clinical response.
Measured: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Changes in self-reported depression as measured by the 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: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Changes in self-reported anxiety as measured by the Generalized Anxiety Disorder (GAD-7) questionnaire
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: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in suicidal intentions
The Scale for Suicide Ideation (SSI) is a brief 19-item scale that assesses the person's current intensity of attitudes, plans, and behaviors to commit suicide. Each question has 3 answer choices. The answer choice suggesting the least suicide intentions is scored as 0, and answer choice suggesting the most suicide intentions are scored as 2.
Total score is determined based on the sum of all individual scores.
Measured: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Choice Reaction Time
Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire.
The first objective cognitive test is called "spotter" and measures choice reaction time by calculating the total time that elapses between the presentation of a stimulus and the occurrence of a response in a task that requires a participant to make one of two different responses depending on which stimuli is presented. Less time between presentation of stimulus and occurrence of a response can be used as an indicator for better reaction time.
Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Working Memory
Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire.
The second objective cognitive test is called "Symbol Check" and is an n-back test. N-back tests measure working memory by presenting the subject with a sequence of stimuli, and the task consists of selecting the stimuli that was presented n steps earlier in the sequence. The greater amount of correct responses can be used as an indicator of better working memory.
Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Digit Symbol Substitution
Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire.
The third objective cognitive test is called "CodeBreaker" and is a Digit Symbol Substitution Test (DSST). DSST involves a key consisting of the numbers 1-6, each paired with a unique symbol. Below the key are a series of the numbers 1-6 in random order and repeated several times. Subjects must select the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured, with higher number of correct symbols indicating greater cognitive function.
Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Trail Making Test part B
Cognitive function will be assessed using the THINC-it brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire.
The fourth objective cognitive test is called "Trails" and is a version of the Trail Making Test part B (TMT-B). The subject is presented with numbers and letters in circles placed in random array on the screen. The subject must draw a line from one circle to the next in ascending order; however, s/he must alternate the circles with numbers in them and circles with letters in them (ie, 1-A-2-B-3-C etc). The TMT is a timed test and the goal is to complete the tests accurately and as quickly as possible. Less time to accurately complete the trial indicates greater cognitive function.
Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Implicit Suicidality
Death Implicit Association Test (D-IAT) is a behavioral test that measures the strength of automatic (implicit) associations between concepts in people's minds relying on latency measures in a simple sorting task. The strength of an association between concepts of "death" and "ones self" is measured by the standardized mean difference score of the 'hypothesis-inconsistent' pairings and 'hypothesis-consistent' pairings
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Clinical Global Impression- Severity
The CGI-Severity scale is clinician rated from 1-7 representing 'Not at all ill' to 'Severely ill'.
Measured: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Clinical Global Impression- Improvement
The CGI-Improvement scale is a clinician rated 1-7, representing the range between 'Very much improved' and 'Very much worse' from the baseline visit.
Measured: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Improvements in depressive symptoms will persist until the 8 week timepoint
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: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Perceived Deficits Questionnaire - 5 item scale (PDQ-5)
Cognitive function will be assessed using the THINC-integrated tool (THINC-it) brief cognitive assessment tool. THINC-it includes a summation of four objective cognitive tests and a subjective cognitive questionnaire.
The cognitive questionnaire is called the Perceived Deficits Questionnaire - 5 item scale (PDQ-5). The questionnaire assesses self perceived cognition by asking questions about attention/concentration, retrospective memory, prospective memory, and planning/organization. Each item is rated on a 5-point scale ranging from 0 (never) to 5 (almost always). Higher scores indicate greater perceived deficits in cognition.
Total results from the THINC-it assessment indicate cognitive performance compared to healthy age-, sex- and education-matched individuals. Change between the two arms will be assessed.
Measured: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2023
- Study start12 Oct 2022
- Primary completion22 Jun 2023
- Study completion22 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexander McGirr, MD PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05731323
- Sponsor's protocol ID
- REB22-0547
- Status last verified
- Sep 2023
- First submitted
- 2 Nov 2022
- Last updated
- 11 Sep 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Study of Adjunctive D-cycloserine to Intermittent Theta Burst Stimulation in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05731323
- Acronym / sponsor ID
- REB22-0547
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 12 Oct 2022 (actual)
- Primary completion
- 22 Jun 2023 (actual)
- Study completion
- 22 Jun 2023 (actual)
- First posted
- 16 Feb 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 \& Rationale: Major Depressive Disorder (MDD) is a common and debilitating illness that that commonly does not respond to conventional treatments. Transcranial magnetic stimulation (TMS) and intermittent theta-burst stimulation (iTBS) are non-invasive neurostimulation treatments for depression that are Health Canada approved. These work by generating magnetic fields outside of the body to change the activity of brain cells to change how the brain works. They have a very favorable profile, with many patients experiencing improvement with minimal side effects.
The investigators recently completed a study pairing iTBS with an FDA approved medication that was chosen because it might enhance iTBS improvements. This medication is called D-cycloserine, an old antibiotic that is rarely used in modern times. Years after it stopped being useful as an antibiotic, scientists recognized other properties that the molecule has, and it is some of these that make it interesting to pair with iTBS. When the investigators did so, they found that compared to iTBS with a placebo, participants who received iTBS+D-cycloserine were more likely to benefit from treatment.
In this original study, all participants received a fixed dose of 100mg daily. This means that people of very different sizes could have had different drug levels, and the investigators do not know how that impacted outcomes. With this study, there will be no placebo condition because the purpose is to understand whether dosing according to weight matters.
Research Question and Objectives: To describe the pharmacokinetic profile of 100mg oral D-cycloserine and weight-based oral D-cycloserine dosed 25mg/17.5kg among individuals with depression undergoing non-invasive intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) in Major Depressive Disorder.
Detailed description
Methods: An open-label study of D-cycloserine (DCS) pharmacokinetics will be performed in patients undergoing iTBS to the left DLPFC as a treatment for Major Depressive Disorder. Twelve patients (males and females aged 18-65, with a score ≥18 on the Hamilton Rating Scale for Depression-17 items, and stable pharmacological and psychological regimens) with an acute Major Depressive Episode will be recruited. Bloodwork and an echocardiogram will be obtained prior to the initiation of the study, and enrollment in the study will be contingent on normal lab results.
Prior to initiating iTBS treatment, participants will receive one oral dose of 100mg DCS. A pharmacokinetic curve will be generated from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs.
Participants will receive iTBS daily for 4 weeks (20 sessions). All participants will be provided with weight-based dosing of DCS to take 120 minutes prior to each iTBS session. Serum levels of weight-based DCS dosing will be measured by blood draws at several time points throughout iTBS treatment. Specifically, a pharmacokinetic curve will be generated on Day 1 of iTBS treatment from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs. Additional time points will be obtained prior to and 120 minutes after the fifth dose (Day 5 of TMS) and prior to and 120 minutes after the sixth dose (Day 6 of TMS, corresponding to the beginning of the second week of TMS).
Antidepressant effects will be quantified using the Montgomery Asberg Depression Rating Scale, a gold standard clinician rated instrument. Participants will complete a short battery of cognitive tests at the beginning and end of the study. Blood work and echocardiogram will be repeated after 4 weeks to confirm safety of low-dose DCS.
Participants will return to the lab for a follow-up assessment 4 weeks after they have finished the TMS protocol (week 8).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Experimental | Drug: D-cycloserine, Device: Transcranial Magnetic StimulatorPrior to initiating TMS therapy, participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine. During TMS therapy, participants will orally ingest a capsule containing a weight-based dose of the antibiotic d-cycloserine (dosed 25mg/17.5kg body weight) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males and females aged 18 to 65 years
- are competent to consent to treatment
- have a confirmed diagnosis of DSM-5 criteria Major Depressive Disorder with a current episode of at least moderate severity of depression, single or recurrent
- have failed to achieve a clinical response to one adequate trial of antidepressant medication within the current episode, or been unable to tolerate antidepressant medications.
- have current episode of at least moderate severity of depression, as defined by a score ≥ 18 on the HAMD-17 item
Key exclusion criteria (18 listed)
- Allergy to cycloserine.
- have failed adequate trials of ≥4 antidepressant treatments in the current episode.
- 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
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-cycloserineAlso: SeromycinDaily oral D-cycloserine dosed 25mg/17.5kg body weight during TMS treatment days (20 days). | Drug | D-Cycloserine |
| Transcranial Magnetic StimulatorRepetitive 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 daily treatments (Monday-Friday) over four weeks. | Device | D-Cycloserine |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
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.
Individual differences in D-cycloserine serum concentration will be correlated with clinical outcomes
Time frame: 10 blood samples: PK curve over the first 2 days of TMS treatment (6 draws) and prior to ingestion and after 120 minutes on day 5 and day 6
Examine whether differential change in clinical outcomes will be mediated by D-Cycloserine plasma levels following weight-based dosing. Participants will provide 10 blood samples to characterize plasma levels of D-Cycloserine following a weight-based dose. The primary efficacy measures will be examined in relation to drug blood levels.
Individual fidelity to the protocol will be correlated with differential change in primary outcomes
Time frame: Daily Monday-Friday throughout study (4 weeks)
All participants will be instructed to take the blinded capsule 90 - 120 minutes prior to TMS treatment, ensuring adequate time for drug absorption. Daily logs will be kept by the study staff to confirm time of capsule ingestion and TMS treatment. Any TMS sessions missed, capsule doses missed and/or capsule doses taken at the incorrect time will be tracked. The primary efficacy measures will be examined in relation to adherence to the protocol (20/20 TMS session completed with oral capsule taken between 90 - 120 minutes prior).
The variance in D-cycloserine level will be greater in the 100mg dosing condition than in the weight-based dosing condition.
Time frame: PK curve done at baseline (fixed dose) and Day 1 of TMS (weight-based dose). Samples at pre-ingestion, +30 minutes, +60 minutes, +90 minutes, +120 minutes, and +24hours.
The maximum serum concentration of D-cycloserine in blood serum will be measured by taking blood samples at various timepoints following oral D-cycloserine. Maximum serum concentration following 100mg oral D-cycloserine and weight-based oral D-cycloserine (dosed 25mg/17.5kg) will be compared. Blood samples will be drawn at baseline (pre-ingestion), +30 minutes, +60 minutes, +90 minutes and +24hours after a uniform dosing of 100mg of D-cycloserine and after a weight-based dosing of 25mg D-cycloserine per 17.5kg of body weight.
Determine whether blood serum levels of D-cycloserine achieved by weight-based dosing is consistent across time.
Time frame: Day 1 of TMS, Day 5 of TMS, and Day 6 of TMS.
Serum concentrations of weight-based oral D-cycloserine (dosed 25mg/17.5kg body weight) will be described by collecting blood samples 120 minutes after ingestion of the first, fifth and sixth dose.
14 secondary outcomes
Number of participants that achieve clinical remission of depression
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Number of participants that achieve clinical response (>=50% improvement in depression)
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Changes in self-reported depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-SR)
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Changes in self-reported anxiety as measured by the Generalized Anxiety Disorder (GAD-7) questionnaire
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in suicidal intentions
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Choice Reaction Time
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Working Memory
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Digit Symbol Substitution
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Trail Making Test part B
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Implicit Suicidality
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Clinical Global Impression- Severity
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Clinical Global Impression- Improvement
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Improvements in depressive symptoms will persist until the 8 week timepoint
Time frame: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Perceived Deficits Questionnaire - 5 item scale (PDQ-5)
Time frame: Administered at baseline, after rTMS treatment (week 4), and at one month follow up (week 8)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2023.
- 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. This study is not recruiting at the moment.
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 1 study testing D-cycloserine and Transcranial Magnetic Stimulator in people with Major Depressive Disorder, 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 18 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: finished, as of the sponsor's last update on 11 Sep 2023. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: Administered at baseline, at the halfway point (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)). The study lists 5 primary outcomes in all. 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 11 Sep 2023; AzTrials last refreshed its copy on 4 Nov 2026.