CompletedNCT02376257Updated Sep 19, 2018Results posted

Improving Therapeutic Learning in Depression: Proof of Concept

A Phase 2 interventional study of 250 mg DCS and 100 mg Modafinil in Major Depressive Disorder, sponsored by Boston University Charles River Campus. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-09-19.

Sponsored by Boston University Charles River Campus · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 36
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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. 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 studied

Major Depressive Disorder

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Keywords

Cognitive behavior therapy (CBT)
d-cycloserine (DCS)
Modafinil

In context

Depressive Disorder

4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.

This study's enrollment of 36 is below the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.

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Lead sponsor

Boston University Charles River Campus is the lead sponsor of 154 studies on the registry; 30 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 8 (57%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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
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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 36 participants (actual)

Study arms

Active comparator
250 mg DCS
Baseline assessment (week 1), two weekly sessions when 250mg DCS is administered, and final week (week 4) when retention is assessed.
Drug: 250 mg DCS
Active comparator
100 mg modafinil
Baseline assessment (week 1), two weekly sessions when 100 mg modafinil is administered, and final week (week 4) when retention is assessed.
Drug: 100 mg Modafinil
Placebo comparator
Placebo
Baseline assessment (week 1), two weekly sessions when placebo is administered, and final week (week 4) when retention is assessed.
Drug: Placebo

Interventions

Drug250 mg DCS
Drug
Also known as: d-cycloserine
Drug100 mg Modafinil
Drug
DrugPlacebo
Drug

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: Week 2 and Week 3

Secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 1, Week 2, Week 3

Results

Posted Sep 19, 2018

Participant flow

Participant flow — Overall Study
Milestone	250 mg DCS	100 mg Modafinil	Placebo
Started	13	12	11
Completed	13	12	11
Not completed	0	0	0

Outcome measures

PrimaryRecall 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.

Time frame:: Week 2 and Week 3
Reported as:: Mean · Number of correct units of information

Recall of Cognitive Therapy Content
Number of correct units of information	250 mg DCS	100 mg Modafinil	Placebo
Week 2	25.4 ± 2.9	26.8 ± 4.0	24.7 ± 4.0
Week 3	28.2 ± 4.2	29.7 ± 3.9	28.7 ± 5.4

Primary1 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.

Time frame:: Week 2 and Week 3
Reported as:: Mean · units on a scale

1 Week Delayed Recall of Emotional Story Items
units on a scale	250 mg DCS	100 mg Modafinil	Placebo
Week 2	13.5 ± 10.4	21.3 ± 8.0	16.1 ± 9.5
Week 3	25.0 ± 13.9	37.3 ± 12.3	26.4 ± 11.9

Primary1 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.

Time frame:: Week 2 and Week 3
Reported as:: Mean · units on a scale

1 Week Delayed Recall Logical Memory
units on a scale	250 mg DCS	100 mg Modafinil	Placebo
Week 2	1.8 ± 2.3	4.4 ± 4.3	5.0 ± 3.8
Week 3	9.5 ± 5.0	12.8 ± 5.5	13.6 ± 5.1

SecondaryLogical 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.

Time frame:: Week 1, Week 2, Week 3
Reported as:: Mean · Number of story units recalled

Logical Memory Immediate Recall
Number of story units recalled	250 mg DCS	100 mg Modafinil	Placebo
Week 1	14.8 ± 4.3	17.1 ± 2.8	16.2 ± 4.7
Week 2	17.7 ± 3.4	17.8 ± 4.1	18.2 ± 2.9
Week 3	18.5 ± 3.0	21.5 ± 2.2	21.2 ± 2.9

SecondaryImmediate 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.

Time frame:: Baseline, Week 1, Week 2, Week 3
Reported as:: Mean · Number of words recalled

Immediate Memory Measured by the Hopkins Verbal Learning Task
Number of words recalled	250 mg DCS	100 mg Modafinil	Placebo
Baseline	8.5 ± 1.3	9.6 ± 1.1	9.6 ± 1.7
Week 1	7.8 ± 1.7	9.9 ± 1.2	9.4 ± 1.5
Week 2	8.7 ± 1.6	9.7 ± 1.3	9.6 ± 1.3
Week 3	8.8 ± 1.8	10.1 ± 1.1	9.4 ± 2.2

SecondaryImmediate 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.

Time frame:: Week 1, Week 2, Week 3
Reported as:: Mean · Number of story units recalled

Immediate Recall of Emotional Story Items
Number of story units recalled	250 mg DCS	100 mg Modafinil	Placebo
Week 1	22.4 ± 11.9	35.2 ± 9.4	32.2 ± 13.3
Week 2	34.4 ± 12.6	46.8 ± 10.9	35.5 ± 11.0
Week 3	38.4 ± 12.9	49.9 ± 12.4	43.4 ± 11.3

SecondarySkills 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.

Time frame:: Week 2 and Week 3
Reported as:: Mean · units on a scale

Skills of Cognitive Therapy
units on a scale	250 mg DCS	100 mg Modafinil	Placebo
Week 2	23.3 ± 6.4	20.5 ± 5.5	24.8 ± 5.6
Week 3	26.4 ± 8.5	24.3 ± 7.2	25.7 ± 4.4

SecondaryDigits 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.

Time frame:: Baseline, Week 1, Week 2, Week 3
Reported as:: Mean · Number of correct trials

Digits Backward
Number of correct trials	250 mg DCS	100 mg Modafinil	Placebo
Baseline	8.3 ± 2.7	9.5 ± 2.5	11.3 ± 2.5
Week 1	9.25 ± 2.8	10.4 ± 2.2	12.2 ± 2.2
Week 2	10.0 ± 3.2	11.3 ± 2.0	12.1 ± 1.7
Week 3	9.6 ± 2.7	11.4 ± 2.2	11.7 ± 2.4

Adverse events

Collected over Adverse events for the visits on which study drugs were administered were assessed at the end of that session and (retrospectively) one week later for events occurring within several hours after that session (at Weeks 2 and 3, and retrospectively at 4). Serious adverse events were reported for the 4-week trial period as a whole.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
250 mg DCS	0/13 (0%)	0/13 (0%)	4/13 (30.8%)
100 mg Modafinil	0/12 (0%)	0/12 (0%)	7/12 (58.3%)
Placebo	0/11 (0%)	0/11 (0%)	7/11 (63.6%)

Most frequent other events

Most frequent other events
Event	250 mg DCS	100 mg Modafinil	Placebo
Fatigue/Low MotivationGeneral disorders	2/13	3/12	5/11
Increased Energy/ConcentrationGeneral disorders	2/13	4/12	2/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	250 mg DCS	100 mg Modafinil	Placebo	Total
<=18 years	0	0	0	0
Between 18 and 65 years	13	12	11	36
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(years)	250 mg DCS	100 mg Modafinil	Placebo	Total
Mean	34.9 ± 14.0	26.4 ± 8.1	27.7 ± 10.8	29.9 ± 11.7

Sex/Gender, Customized
Sex/Gender, Customized(Participants)	250 mg DCS	100 mg Modafinil	Placebo	Total
Male	5	5	4	14
Female	7	6	7	20
Transgender	1	1	0	2

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	250 mg DCS	100 mg Modafinil	Placebo	Total
Hispanic or Latino	3	0	2	5
Not Hispanic or Latino	10	12	9	31
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	250 mg DCS	100 mg Modafinil	Placebo	Total
American Indian or Alaska Native	0	0	0	0
Asian	2	2	3	7
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	2	1	2	5
White	8	9	5	22
More than one race	0	0	0	0
Unknown or Not Reported	1	0	1	2

Immediate Memory measured by the Hopkins Verbal Learning Task
Immediate Memory measured by the Hopkins Verbal Learning Task(number of correctly recalled words)	250 mg DCS	100 mg Modafinil	Placebo	Total
Mean	8.5 ± 1.3	9.6 ± 1.1	9.6 ± 1.7	9.2 ± 1.4

Digits backwards
Digits backwards(Number of correct trials)	250 mg DCS	100 mg Modafinil	Placebo	Total
Mean	8.3 ± 2.7	9.5 ± 2.5	11.3 ± 2.5	9.6 ± 2.8

Study locations

1 site

Boston University
Boston, Massachusetts 02215, United States

References and documents

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 documents

Study protocol · Nov 15, 2013
Statistical analysis plan · Nov 15, 2013

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02376257
Lead sponsor: Boston University Charles River Campus
Responsible party: Michael Otto (Ph.D., Boston University Charles River Campus) — Principal investigator
First posted: Mar 3, 2015
Start date: Sep 16, 2014
Primary completion: Apr 21, 2017
Completion: May 2017
Results posted: Sep 19, 2018
Last update: Sep 19, 2018

Study contacts

Michael W Otto, Ph. D

principal investigator · Boston University

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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