Major Depressive DisorderPhase 2NCT02376257
Improving Therapeutic Learning in Depression: Proof of Concept
A Phase 2 study testing 250 mg DCS and 100 mg Modafinil in people with Major Depressive Disorder, run by Boston University Charles River Campus at 1 site in United States.
Trial summary
Despite advances in both pharmacotherapy and psychotherapy for major depression, non-response and partial-response remain relatively common outcomes, motivating the search for new treatments. 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?
- 250 mg DCS and 100 mg Modafinil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2014to May 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Must have a DSM diagnosis of major depression as determined by structured diagnostic interview
- Must be free of psychotropic medications other than serotonin selective reuptake inhibitors (SSRIs) for at least 2 weeks
- No current suicidal ideation
- Able to speak and understand English
- Must be between the ages of 18 and 65, inclusive
- Must be a male, or a female who is not of childbearing potential (i.e., surgically sterile, postmenopausal for at least 1 year) or who is non-pregnant, non-lactating and using a medically accepted method of contraception. Acceptable methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, hormonal contraceptives. A woman of childbearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the trial
Who cannot join
- A DSM diagnosis of dementia, neurodegenerative disease, or other organic mental disorder; substance use disorder other than nicotine or caffeine in the last 3 months; bulimia or anorexia within the last 3 months; lifetime history of psychotic disorder or, bipolar disorder, or developmental disorder;
- A diagnosis of organic brain syndrome, mental retardation, or other cognitive dysfunction that could interfere with a participants capacity to participate in CBT or to complete safety and efficacy assessments
- A history of seizures (apart from childhood febrile seizures) or head trauma causing ongoing cognitive impairment
- An uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy, or poorly controlled hypertension (> 150/90mmHg) that may interfere with the interpretation of safety and efficacy evaluations in the opinion of the study physician or investigator
- Medical illness including hypertension, cardiac disease, liver disease, pulmonary diseases, central nervous system disease, and epilepsy;
- Recent (1 year) suicidal attempts or current suicidal ideation
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- For women, currently pregnant, plans to be pregnant in the next 2 months, or currently breastfeeding
- Treatment with phenytoin, isoniazid, or propranolol or known sensitivity to modafinil or cycloserine
- A history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment
- Use of psychotropic medication (including stimulants) other than SSRIs
- Current daily use of alcohol or regular binge alcohol use as determined on the medical screen
- Insufficient command of the English language (i.e., cannot carry on a conversation with an interviewer in the English language or read associated text)
- Receipt of CBT in the previous five years
Trial locations and contacts
1 site in 1 country.
About this study
Despite advances in both pharmacotherapy and psychotherapy for major depression, non-response and partial-response remain relatively common outcomes, motivating the search for new treatments. This study is concerned with the development of one such novel treatment, the augmentation of exposure-based cognitive-behavior therapy (CBT) with d-cycloserine (DCS).
Read the detailed description
Investigators will study the efficacy of DCS for augmenting therapeutic learning relevant for the treatment of depression (i.e., outside the extinction learning where DCS has been shown to have success). Specifically, the study investigates the role of DCS in enhancing declarative memory in depressed individuals, as evaluated by standardized tests and the retention of cognitive therapy session material. Investigators will also study an active comparison agent, modafinil, which appears to offer cognitive enhancing effects among both sleep-deprived and non-sleep-deprived individuals, but also appears to have drug-state (e.g., mood and side) effects that are not characteristic of DCS augmentation. Therefore, drug-context effects may affect memory retention over time. Hence, the study will evaluate memory enhancement effects both during the period of drug action as well as one week later when no drug is taken. Overall, investigators will examine cognitive function and memory performance over 4 study sessions in 96 men and women with major depression, who, in a double-blind fashion, will be randomly assigned to either: (1) 250mg DCS, (2) 100mg modafinil, or (3) placebo administered on Study Weeks 2 and 3. The memory tests include both items unique to a given study week and memory tasks that are repeated over time that allow assessment of memory and retention effects across one-week periods.
- Conditions
- Major Depressive Disorder
- Being tested
- 250 mg DCS, 100 mg Modafinil, Placebo
- Keywords
- Cognitive behavior therapy (CBT), d-cycloserine (DCS), Modafinil
- 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.
250 mg DCSDrug
Also called d-cycloserine
Drug
100 mg ModafinilDrug
Drug
PlaceboDrug
Drug
| Study group | Role | What they receive |
|---|---|---|
| 250 mg DCS | Active comparator | Baseline assessment (week 1), two weekly sessions when 250mg DCS is administered, and final week (week 4) when retention is assessed. Receives: Drug: 250 mg DCS |
| 100 mg modafinil | Active comparator | Baseline assessment (week 1), two weekly sessions when 100 mg modafinil is administered, and final week (week 4) when retention is assessed. Receives: Drug: 100 mg Modafinil |
| Placebo | Placebo comparator | Baseline assessment (week 1), two weekly sessions when placebo is administered, and final week (week 4) when retention is assessed. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recall of Cognitive Therapy Content
A modified Cognitive Therapy Awareness Scale (CTAS) was used to assess delayed memory for cognitive therapy content from the computerized CBT. Higher scores indicate better memory for CBT skills. Scores range from 0 to 40.
Measured: Week 2 and Week 3
1 Week Delayed Recall of Emotional Story Items
1 Week Delayed Recall of a Threat-Related Story. Scores can range from 0 to 74, with higher scores reflect greater memory for story items.
Measured: Week 2 and Week 3
1 Week Delayed Recall Logical Memory
Higher scores reflect greater recall of Wechsler Memory Scale (WMS) Story B content assessed one week after last rehearsal. Possible scores range from 0 to 25.
Measured: Week 2 and Week 3
Secondary outcomes (5)
Logical Memory Immediate Recall
Immediate Story Recall from the Wechsler Memory Scale Story B. Higher scores reflect greater recall of the story material from the previous week. Possible scores range from 0 to 25.
Measured: Week 1, Week 2, Week 3
Immediate Memory Measured by the Hopkins Verbal Learning Task
The Hopkins Verbal Learning Test (HVLT) consists of a 12-item word list, composed of four words from each of the three semantic categories. The patient's free recall of the list is recorded. The same procedure is repeated for two more trials. The total recall score for the third trial was used as the recorded score and ranged from a minimum of zero to a maximum of 12 correct answers.
Measured: Baseline, Week 1, Week 2, Week 3
Immediate Recall of Emotional Story Items
Immediate recall score of items from the Emotional Story presentation. Scores can range from 0 to 74, with higher scores reflect greater memory for story items.
Measured: Week 1, Week 2, Week 3
Skills of Cognitive Therapy
This measure assesses the self-reported use of skills from cognitive therapy. Scores can range from 8 to 40, and higher scores indicate greater use.
Measured: Week 2 and Week 3
Digits Backward
The examiner reads a list of digits and asks that each digit be read backwards. The score is the total number of trials completed correctly; scores range from 0 to 16. Higher scores indicate better performance.
Measured: Baseline, Week 1, Week 2, Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study start16 Sep 2014
- Primary completion21 Apr 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University Charles River Campus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Otto, Boston University Charles River Campus
- Investigators
- Michael W Otto, Ph. D, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02376257
- Sponsor's protocol ID
- R21MH102646
- Status last verified
- Aug 2018
- First submitted
- 11 Jul 2014
- Last updated
- 19 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Otto MW, Lee J, Hofmann SG, Hearon BA, Smits JA, Rosenfield D, Fava M, Wright JH. Examining the efficacy of d-cycloserine to augment therapeutic learning in depression. Contemp Clin Trials. 2016 May;48:146-52. doi: 10.1016/j.cct.2016.03.009. Epub 2016 Apr 16.
PubMed 27094721
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Therapeutic Learning in Depression: Proof of Concept
- ClinicalTrials.gov ID
- NCT02376257
- Acronym / sponsor ID
- R21MH102646
- Conditions
- Major Depressive Disorder
- Keywords
- Cognitive behavior therapy (CBT), d-cycloserine (DCS), Modafinil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Boston University Charles River CampusUniversity, hospital or other
- Study start
- 16 Sep 2014 (actual)
- Primary completion
- 21 Apr 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Posted 19 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite advances in both pharmacotherapy and psychotherapy for major depression, non-response and partial-response remain relatively common outcomes, motivating the search for new treatments. This study is concerned with the development of one such novel treatment, the augmentation of exposure-based cognitive-behavior therapy (CBT) with d-cycloserine (DCS).
Detailed description
Investigators will study the efficacy of DCS for augmenting therapeutic learning relevant for the treatment of depression (i.e., outside the extinction learning where DCS has been shown to have success). Specifically, the study investigates the role of DCS in enhancing declarative memory in depressed individuals, as evaluated by standardized tests and the retention of cognitive therapy session material. Investigators will also study an active comparison agent, modafinil, which appears to offer cognitive enhancing effects among both sleep-deprived and non-sleep-deprived individuals, but also appears to have drug-state (e.g., mood and side) effects that are not characteristic of DCS augmentation. Therefore, drug-context effects may affect memory retention over time. Hence, the study will evaluate memory enhancement effects both during the period of drug action as well as one week later when no drug is taken. Overall, investigators will examine cognitive function and memory performance over 4 study sessions in 96 men and women with major depression, who, in a double-blind fashion, will be randomly assigned to either: (1) 250mg DCS, (2) 100mg modafinil, or (3) placebo administered on Study Weeks 2 and 3. The memory tests include both items unique to a given study week and memory tasks that are repeated over time that allow assessment of memory and retention effects across one-week periods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 250 mg DCS | Active comparator | Drug: 250 mg DCSBaseline assessment (week 1), two weekly sessions when 250mg DCS is administered, and final week (week 4) when retention is assessed. |
| 100 mg modafinil | Active comparator | Drug: 100 mg ModafinilBaseline assessment (week 1), two weekly sessions when 100 mg modafinil is administered, and final week (week 4) when retention is assessed. |
| Placebo | Placebo comparator | Drug: PlaceboBaseline assessment (week 1), two weekly sessions when placebo is administered, and final week (week 4) when retention is assessed. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Must have a DSM diagnosis of major depression as determined by structured diagnostic interview
- Must be free of psychotropic medications other than serotonin selective reuptake inhibitors (SSRIs) for at least 2 weeks
- No current suicidal ideation
- Able to speak and understand English
- Must be between the ages of 18 and 65, inclusive
Key exclusion criteria (13 listed)
- A DSM diagnosis of dementia, neurodegenerative disease, or other organic mental disorder; substance use disorder other than nicotine or caffeine in the last 3 months; bulimia or anorexia within the last 3 months; lifetime history of psychotic disorder or, bipolar disorder, or developmental disorder;
- A diagnosis of organic brain syndrome, mental retardation, or other cognitive dysfunction that could interfere with a participants capacity to participate in CBT or to complete safety and efficacy assessments
- A history of seizures (apart from childhood febrile seizures) or head trauma causing ongoing cognitive impairment
- An uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic or cerebrovascular disease, or malignancy, or poorly controlled hypertension (> 150/90mmHg) that may interfere with the interpretation of safety and efficacy evaluations in the opinion of the study physician or investigator
- Medical illness including hypertension, cardiac disease, liver disease, pulmonary diseases, central nervous system disease, and epilepsy;
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 |
|---|---|---|
| 250 mg DCSAlso: d-cycloserineDrug | Drug | 250 mg DCS |
| 100 mg ModafinilDrug | Drug | 100 mg modafinil |
| PlaceboDrug | Drug | Placebo |
Primary outcome
Recall of Cognitive Therapy Content
Time frame: Week 2 and Week 3
A modified Cognitive Therapy Awareness Scale (CTAS) was used to assess delayed memory for cognitive therapy content from the computerized CBT. Higher scores indicate better memory for CBT skills. Scores range from 0 to 40.
1 Week Delayed Recall of Emotional Story Items
Time frame: Week 2 and Week 3
1 Week Delayed Recall of a Threat-Related Story. Scores can range from 0 to 74, with higher scores reflect greater memory for story items.
1 Week Delayed Recall Logical Memory
Time frame: Week 2 and Week 3
Higher scores reflect greater recall of Wechsler Memory Scale (WMS) Story B content assessed one week after last rehearsal. Possible scores range from 0 to 25.
5 secondary outcomes
Logical Memory Immediate Recall
Time frame: Week 1, Week 2, Week 3
Immediate Memory Measured by the Hopkins Verbal Learning Task
Time frame: Baseline, Week 1, Week 2, Week 3
Immediate Recall of Emotional Story Items
Time frame: Week 1, Week 2, Week 3
Skills of Cognitive Therapy
Time frame: Week 2 and Week 3
Digits Backward
Time frame: Baseline, Week 1, Week 2, Week 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27094721Otto MW, Lee J, Hofmann SG, Hearon BA, Smits JA, Rosenfield D, Fava M, Wright JH. Examining the efficacy of d-cycloserine to augment therapeutic learning in depression. Contemp Clin Trials. 2016 May;48:146-52. doi: 10.1016/j.cct.2016.03.009. Epub 2016 Apr 16.
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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.
Michael W Otto, Ph. D principal investigator
Boston University
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 250 mg DCS and 100 mg Modafinil in people with Major Depressive Disorder, run by Boston University Charles River Campus at 1 site in United States.
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 6 inclusion and 13 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 19 Sep 2018. 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 United States. 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?
Yes. Results are posted in the registry (first posted 19 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Recall of Cognitive Therapy Content (time frame: Week 2 and Week 3). The study lists 3 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 NCT02376257, 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 19 Sep 2018.