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Improving Therapeutic Learning in Depression: Proof of Concept

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02376257
Recruitment Status : Completed
First Posted : March 3, 2015
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
Michael Otto, Boston University Charles River Campus

Brief 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).

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: 250 mg DCS Drug: 100 mg Modafinil Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Improving Therapeutic Learning in Depression: Proof of Concept
Actual Study Start Date : September 16, 2014
Actual Primary Completion Date : April 21, 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug
Other Name: d-cycloserine

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
Drug

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
Drug




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. Logical Memory Immediate Recall [ Time Frame: Week 1, Week 2, Week 3 ]
    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.

  2. Immediate Memory Measured by the Hopkins Verbal Learning Task [ Time Frame: Baseline, Week 1, Week 2, Week 3 ]
    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.

  3. Immediate Recall of Emotional Story Items [ Time Frame: Week 1, Week 2, Week 3 ]
    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.

  4. Skills of Cognitive Therapy [ Time Frame: Week 2 and Week 3 ]
    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.

  5. Digits Backward [ Time Frame: Baseline, Week 1, Week 2, Week 3 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02376257


Locations
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United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Boston University Charles River Campus
Investigators
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Principal Investigator: Michael W Otto, Ph. D Boston University
  Study Documents (Full-Text)

Documents provided by Michael Otto, Boston University Charles River Campus:
Study Protocol  [PDF] November 15, 2013
Statistical Analysis Plan  [PDF] November 15, 2013

Publications:
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Responsible Party: Michael Otto, Ph.D., Boston University Charles River Campus
ClinicalTrials.gov Identifier: NCT02376257    
Other Study ID Numbers: R21MH102646 ( U.S. NIH Grant/Contract )
First Posted: March 3, 2015    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Otto, Boston University Charles River Campus:
Cognitive behavior therapy (CBT)
d-cycloserine (DCS)
Modafinil
Additional relevant MeSH terms:
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Depressive Disorder
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Cycloserine
Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites