Major Depressive DisorderPhase 2NCT00408031
D-cycloserine for Major Depressive Disorder
A Phase 2 study testing D-cycloserine in people with Major Depressive Disorder, run by Herzog Hospital at 2 sites in Israel.
Trial summary
For many depression patients treatment changes are required, including switching to another antidepressant and addition of a second antidepressant or a non-antidepressant agent ("augmentation"). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- D-cycloserine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesIsrael
- Study dates
- Jan 2007to May 2010
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DSM-IV diagnosis of major depression .
- HAMD scale score of ≥20 despite at least two adequate antidepressant treatment trials during the current episode.
Who cannot join
- Underwent ECT treatment during the 3 months preceding the study.
- Change in psychotropic medications doses during the 3 weeks preceding the study.
- Concurrent unstable medical or neurological illness.
- Patients are judged to be potentially violent towards themselves or others, or have a history of drug/alcohol abuse.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
Jerusalem
Ezrath Nashim - Herzog Memorial Hospital
Jerusalem
About this study
Official title: N-methyl-D-aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-cycloserine for Treatment-resistant Major Depressive Disorder
For many depression patients treatment changes are required, including switching to another antidepressant and addition of a second antidepressant or a non-antidepressant agent ("augmentation"). The need to modify treatment is usually necessary because of partial or no response to first-line monotherapy or the failure to achieve remission although treatment response (improvement) has been obtained. These caveats of presently available antidepressant drugs highlight the need for innovative pharmacological treatment strategies. Recent data suggest that N-methyl-D-aspartate receptor (NMDAR) antagonists and partial agonists at the NMDAR-associated glycine binding site may represent a novel type of antidepressant medications. These types of compounds protect vulnerable neurons against a variety of insults, including stress-induced damage, and may serve to enhance and maintain normal synaptic connectivity. In animal models, these compounds mimic the effects of clinically effective antidepressants. Furthermore, down-regulation of the glycine site of the NMDAR was found to be a common feature of currently used antidepressant medications. D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated glycine site. Beneficial antidepressant effects have been reported with 500-1000 mg/day DCS regimens in depressed tuberculosis patients and recent preliminary findings suggest that DCS may also be beneficial in the treatment of major depressive disorder. The antidepressant effects of DCS seem to reflect consequences of its capacity to reduce NMDAR receptor function. In the present project, it is proposed to assess, using a random assignment, parallel-group, double blind, placebo controlled design, the effects of a NMDAR -antagonist DCS dose regimen, 250 --> 1000 mg/day for 6 wks, as adjuvant pharmacotherapy for treatment-resistant major depressive disorder patients. The study methodology includes the assessment of DCS effects upon symptoms profile, neurocognitive tests performance, amino acids serum levels, and brain electrophysiology parameters associated with the prepulse inhibition-startle response paradigm. It is hypothesized that significant beneficial DCS treatment effects will be registered.
- Conditions
- Major Depressive Disorder
- Being tested
- D-cycloserine
- Keywords
- Major depressive disorder, NMDA receptor, Treatment-Resistant, D-cycloserine
- 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
D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated GLY site.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Randomization to 2 treatment groups. One group receives adjuvant treatment with D-cycloserine, up to 1 g/day. The second group receives adjuvant treatment with placebo, up to 1 g/day. Receives: Drug: D-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA)
Measured: 6 weeks
Change in Hamilton Rating Scale for Anxiety (HAMA) scores.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2006 (estimated)
- Study startJan 2007
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herzog Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Principal investigator, Heresco-Levi Uriel, Herzog Hospital
- Investigators
- Uriel Heresco-Levy, M.D., Principal investigator, Ezrath Nashim - Herzog Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00408031
- Sponsor's protocol ID
- Heresco 4 CTIL
- Other IDs
- Herzog - protocol 5372
- Status last verified
- Aug 2012
- First submitted
- 3 Dec 2006
- Last updated
- 3 Aug 2012
- Results posted
- No
Publications
Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.
PubMed 34510411
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-methyl-D-aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-cycloserine for Treatment-resistant Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT00408031
- Acronym / sponsor ID
- Heresco 4 CTIL
- Conditions
- Major Depressive Disorder
- Keywords
- Major depressive disorder, NMDA receptor, Treatment-Resistant, D-cycloserine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Herzog HospitalUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Jan 2007
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 5 Dec 2006 (estimated)
- 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.
For many depression patients treatment changes are required, including switching to another antidepressant and addition of a second antidepressant or a non-antidepressant agent ("augmentation"). The need to modify treatment is usually necessary because of partial or no response to first-line monotherapy or the failure to achieve remission although treatment response (improvement) has been obtained. These caveats of presently available antidepressant drugs highlight the need for innovative pharmacological treatment strategies. Recent data suggest that N-methyl-D-aspartate receptor (NMDAR) antagonists and partial agonists at the NMDAR-associated glycine binding site may represent a novel type of antidepressant medications. These types of compounds protect vulnerable neurons against a variety of insults, including stress-induced damage, and may serve to enhance and maintain normal synaptic connectivity. In animal models, these compounds mimic the effects of clinically effective antidepressants. Furthermore, down-regulation of the glycine site of the NMDAR was found to be a common feature of currently used antidepressant medications. D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated glycine site. Beneficial antidepressant effects have been reported with 500-1000 mg/day DCS regimens in depressed tuberculosis patients and recent preliminary findings suggest that DCS may also be beneficial in the treatment of major depressive disorder. The antidepressant effects of DCS seem to reflect consequences of its capacity to reduce NMDAR receptor function. In the present project, it is proposed to assess, using a random assignment, parallel-group, double blind, placebo controlled design, the effects of a NMDAR -antagonist DCS dose regimen, 250 --> 1000 mg/day for 6 wks, as adjuvant pharmacotherapy for treatment-resistant major depressive disorder patients. The study methodology includes the assessment of DCS effects upon symptoms profile, neurocognitive tests performance, amino acids serum levels, and brain electrophysiology parameters associated with the prepulse inhibition-startle response paradigm. It is hypothesized that significant beneficial DCS treatment effects will be registered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: D-cycloserineRandomization to 2 treatment groups. One group receives adjuvant treatment with D-cycloserine, up to 1 g/day. The second group receives adjuvant treatment with placebo, up to 1 g/day. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- DSM-IV diagnosis of major depression .
- HAMD scale score of ≥20 despite at least two adequate antidepressant treatment trials during the current episode.
Key exclusion criteria (4 listed)
- Underwent ECT treatment during the 3 months preceding the study.
- Change in psychotropic medications doses during the 3 weeks preceding the study.
- Concurrent unstable medical or neurological illness.
- Patients are judged to be potentially violent towards themselves or others, or have a history of drug/alcohol abuse.
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-cycloserineD-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated GLY site. | Drug | 1 |
Primary outcome
Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA)
Time frame: 6 weeks
Change in Hamilton Rating Scale for Anxiety (HAMA) scores.
Time frame: 6 weeks
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 3 Aug 2012.
- Derived from this study: PubMed 34510411Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.
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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.
Uriel Heresco-Levy, M.D. principal investigator
Ezrath Nashim - Herzog Memorial Hospital
2 sites 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 in people with Major Depressive Disorder, run by Herzog Hospital at 2 sites in Israel.
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 2 inclusion and 4 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 3 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. 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 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?
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?
Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA) (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00408031, which also lists 1 linked publication.
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 3 Aug 2012.