Improving Therapeutic Learning in Depression: Proof of Concept

NCT02376257 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: R21MH102646
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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).

Conditions

Major Depressive Disorder

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Week 2 and Week 3

Secondary Outcomes (5)

• Logical Memory Immediate Recall

  Week 1, Week 2, Week 3

• Immediate Memory Measured by the Hopkins Verbal Learning Task

  Baseline, Week 1, Week 2, Week 3

• Immediate Recall of Emotional Story Items

  Week 1, Week 2, Week 3

• Skills of Cognitive Therapy

  Week 2 and Week 3

• Digits Backward

  Baseline, Week 1, Week 2, Week 3

Study Arms (3)

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.

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.

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.

Drug: Placebo

Interventions

250 mg DCS DRUG

Drug

Also known as: d-cycloserine

250 mg DCS

100 mg Modafinil DRUG

Drug

100 mg modafinil

Placebo DRUG

Drug

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston University Charles River Campus: lead

Study Sites (1)

Boston University

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 27094721 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Cycloserine; Modafinil

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Michael Otto, PhD
• Organization: Boston UCRC

mwotto@bu.edu

617-353-9610

Study Officials

• Michael W Otto, Ph. D

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D.

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: March 3, 2015
• Study Start: September 16, 2014
• Primary Completion: April 21, 2017
• Study Completion: May 1, 2017
• Last Updated: September 19, 2018
• Results First Posted: September 19, 2018

Record last verified: 2018-08

Locations

US (1)