A Randomized Controlled Trial of Cognitive Remediation and D-cycloserine for Individuals With Bipolar Disorder (DCS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Arizona
Sponsor:
Information provided by (Responsible Party):
Nicholas Breitborde, University of Arizona
ClinicalTrials.gov Identifier:
NCT01934972
First received: August 19, 2013
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

Individuals with bipolar suffer from problems in basic cognitive skills such as memory and concentration. Unfortunately, there are no current treatments that have been shown to improve cognitive skills among individuals with bipolar disorder.

Computerized cognitive remediation (CR) is a treatment that has been shown to improve cognitive skills among individuals with serious mental illnesses other than bipolar disorder, such as schizophrenia. This treatment involves completing a series of activities on a computer that have been shown to improve cognitive skills.

D-cycloserine (DCS) is an antibiotic traditionally used in the treatment of tuberculosis. Recent studies have suggested that this drug may also improve individuals' ability to learn. Thus, the goal of our study is to examine whether receipt of d-cycloserine increases the benefit that individuals receive from participation in cognitive remediation.

To test this hypothesis, approximately forty subjects will be randomized to one of two study arms: [i] CR + DCS or [ii] CR + placebo. We will examine whether d-cycloserine increases the benefit that individuals with bipolar disorder receive from participation in cognitive remediation.


Condition Intervention Phase
Bipolar Disorder
Other: CR + DCS (D-cycloserine)
Other: CR + placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Cognitive Remediation and D-cycloserine for Individuals With Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Change from baseline in cognitive functioning [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

    Level of cognitive functioning will be assessed via the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery & Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) battery.

    Per existing recommendations for assessment of cognition in individuals w/bipolar disorder, the MATRICS battery will be supplement with (i) the California Verbal Learning Test; (ii) the Stroop Test; (iii) Trail Making Test-part B; and (iv) Wisconsin Card Sorting Test



Secondary Outcome Measures:
  • Change from baseline in Manic Symptomatology [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Manic symptomatology assesed using the Yung Mania Sclare and the Altman Self-Rating Mania Scale

  • Change from baseline in Depressive Symptomatology [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Depressive symptomatology assessed using the Inventory or Depressive Symptomatology (Clinician-Rated), Inventory for Depressive Symptomatology (Self-Rated), and Bipolar Depression Rating Scale

  • Change from Baseline in Social Functioning [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Social functioning assessed using the Social Functioning Scale

  • Change from Baseline in Performance of Tasks of Everyday Living [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Performances of tasks of everyday living assessed using the Brief University of California, San Diego Performance-Based Skills Assessment and the Specific Level of Functioning Assessment Scale

  • Change from baseline in emotional, motor, and sensory functioning [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Assessed using the NIH Toolbox


Other Outcome Measures:
  • Change from baseline in health-related quality of life [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Health-related quality of life assessed using the RAND 36-Item Health Survey

  • Change from baseline in service utilization [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Service utilization assessed using the Service Utilization and Resources Form

  • Change from baseline in medication adherence [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Medication adherence assessed using the Medication Adherence Rating Scale

  • Change from baseline in quality of life [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    Quality of life assessed using the World Health Organization Quality of Life Scale

  • Change from baseline in stage of recovery [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Stage of recovery assessed using the Stages of Recovery Instrument

  • Change from baseline in personality traits [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Personality traits assessed using the Ten Item Personality Inventory

  • Change from baseline in metacognition [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Metacognition assessed using the Metacognitive Awareness Inventory

  • Change in instrinsic motivation from baseline [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Intrinsic motivation assessed using the Intrinsic Motivation Inventory

  • Frequency of side effects during study participation [ Time Frame: 26 Weeks ] [ Designated as safety issue: Yes ]
    Assessed using the Systematic Assessment for Treatment Emergent Events


Estimated Enrollment: 40
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CR + DCS
Subjects will receive Cognitive Remediation and active study drug.
Other: CR + DCS (D-cycloserine)
CR + DCS
Other Name: DCS and Cognitive Remediation
Active Comparator: CR + placebo
Cognitive Remediation and placebo
Other: CR + placebo
CR + placebo
Other Name: Cognitive Remediation

Detailed Description:

Individuals with bipolar disorder suffer from a broad array of cognitive deficits that may hinder their ability to achieve successful community functioning. Consequently, greater attention has recently been directed toward the development of strategies to ameliorate these cognitive deficits. One strategy which has been shown to be successful in this endeavor is cognitive remediation (CR). This intervention, which is recognized as a "best practice" in the treatment of serious mental illness, is typically comprised of a series of repeated exercises delivered by a clinician or via a computer that are designed to improve performance in cognitive functioning. Yet, despite the promise of cognitive remediation, the benefit of this intervention among individuals with bipolar disorder has yet to be investigated.

Recently, studies have demonstrated that d-cycloserine (DCS), an N-methyl-D-aspartate receptor (NMDAR) agonist, may facilitate the learning process for emotional and non-emotional information in both humans and animals. These results raise the possibility that DCS may increase the benefits associated with the receipt of cognitive remediation among individuals with bipolar disorder. To date, we are unaware of any study which has examined whether concurrent receipt of DCS may increase the benefits produced by cognitive remediation among individuals with a severe mental illness.

Thus, we propose to complete an exploratory investigation of augmenting cognitive remediation with DCS among individuals with bipolar disorder. Approximately forty subjects will be randomized to one of two study arms: [i] CR + DCS; or [ii] CR + placebo. The primary outcome of interest will be changes in cognitive functioning before and after receipt of the cognitive remediation intervention. Secondary outcomes of interest will be changes in symptomatology, social and vocational functioning, and performance of tasks of everyday living.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

- Inclusion Criteria: [i] Diagnosis of Bipolar I or Bipolar II Disorder determined by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM) [ii] Ages 18-65 [iii] No evidence of mental retardation, dementia, or other organic disorder that may reduce cognitive functioning [iv] premorbid intelligence quotient (IQ) greater than or equal to 70 as determined by reading subtest of the Wide Range Achievement Test.

[v] Able to provide informed consent as evidenced by passing the informed consent quiz with a score of 80% or greater.

[vi] Fluent in English as assessed per self-report from participant [vii] Female subjects cannot be pregnant or breastfeeding. All subjects must consent to using at least one form of birth control during study participation.

[viii] Current remission of depressive symptoms as indicated by a score of 8 or less on the Bipolar Depression Rating Scale.

[ix] Current remission of manic symptoms as indicated by a score of 7 or less on the Young Mania Scale

Exclusion criteria:

[i] Hypersensitivity to previous receipt of cycloserine per subject report [ii] Epilespy or history of seizures as assessed using the Medical History form [iii] Meets DSM-IV criteria for alcohol or drug abuse in the past month or dependence in the past three months.

[iv] Active suicidal or homicidal ideation [v] Initiation or increase in dosage of any antidepressant within six weeks, or mood stabilizer within four weeks as assessed using the Medication Checklist.

[vi] Previous or current participation in cognitive remediation per subject report [vii] Currently taking d-cycloserine [viii] Reduced kidney or liver functioning, vitamin B12 deficiency, folic acid deficiency, megaloblastic anemia, or sideroblastic anemia per baseline safety labs.

[ix] Currently taking medication known to have problematic interactions with d-cycloserine, including etionamide and isoniazid.

[x] History of the blood disease porphyria as assessed using the Medical History form [xi] Current active symptoms of psychosis defined as not meeting existing guidelines [12] for remission of psychotic symptoms using the Positive and Negative Syndrome Scale.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01934972

Contacts
Contact: Nicholas Breitborde, PhD 520-874-7531 breitbor@email.arizona.edu
Contact: Joseph Yee, BS 520-626-5105 jyee@psychiatry.arizona.edu

Locations
United States, Arizona
University of Arizona Medical Center South Campus Recruiting
Tucson, Arizona, United States, 85713
Principal Investigator: Nicholas Breitborde, PhD         
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Nicholas Breitborde, PhD The University of Arizona
  More Information

No publications provided

Responsible Party: Nicholas Breitborde, Assistant Professor, Psychiatry, University of Arizona
ClinicalTrials.gov Identifier: NCT01934972     History of Changes
Other Study ID Numbers: 12-0926-01 Breitborde DCS
Study First Received: August 19, 2013
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arizona:
Bipolar disorder

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014