Improving Therapeutic Learning in Depression: Proof of Concept
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Intervention: 250 mg DCS; 100 mg Modafinil; Placebo
Intervention description: Drug; Drug; Drug
Intervention MeSH terms: Cycloserine; Modafinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Cognitive behavior therapy (CBT); d-cycloserine (DCS); Modafinil

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).
    

Eligibility 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