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

NCT01934972 | Completed Phase 3 Results DMC

• 1 other identifier: 12-0926-01 Breitborde DCS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Disorder

Keywords

Bipolar disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Cognitive Functioning

  Level of cognitive functioning will be assessed via overall cognitive composite score from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery. Scores on the MATRICS are presented at T-scores with a mean of 50 and standard deviation of 10 as compared to a normative sample. The possible range of scores are 0-100. Higher scores are indicative of better cognitive functioning. Change from baseline in cognitive functioning was calculated by taking the MATRICS overall cognitive functioning score at 26-week follow-up and subtracting the MATRICS overall cognitive composite score from baseline. Positive values on this score are indicative of improvements in cognitive functioning from baseline. Missing values on the MATRICS were addressed using multiple imputation

  26 weeks

Secondary Outcomes (4)

• Change From Baseline in Manic Symptomatology

  26 weeks

• Change From Baseline in Depressive Symptomatology

  26 Weeks

• Change From Baseline in Social Functioning

  26 Weeks

• Change From Baseline in Functional Capacity

  26 Weeks

Other Outcomes (7)

• Change From Baseline in Health-related Quality of Life

  26 weeks

• Change From Baseline in Medication Adherence

  26 Weeks

• Change From Baseline in Quality of Life

  26 Weeks

Study Arms (2)

CR + DCS

EXPERIMENTAL

Subjects will receive Cognitive Remediation and active study drug.

Other: CR + DCS (D-cycloserine)

CR + placebo

ACTIVE COMPARATOR

Cognitive Remediation and placebo

Other: CR + placebo

Interventions

CR + DCS (D-cycloserine) OTHER

CR + DCS

Also known as: DCS and Cognitive Remediation

CR + DCS

CR + placebo OTHER

CR + placebo

Also known as: Cognitive Remediation

CR + 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:

• \[v\] 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

You may not qualify if:

• \[i\] 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.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Medical Center South Campus

Tucson, Arizona, 85713, United States

Location

Related Publications (1)

• Breitborde NJ, Dawson SC, Woolverton C, Dawley D, Bell EK, Norman K, Polsinelli A, Bernstein B, Mirsky P, Pletkova C, Grucci F 3rd, Montoya C, Nanadiego B, Sarabi E, DePalma M, Moreno F. A randomized controlled trial of cognitive remediation and d-cycloserine for individuals with bipolar disorder. BMC Psychol. 2014 Oct 10;2(1):41. doi: 10.1186/s40359-014-0041-4. eCollection 2014.

  PMID: 25566387 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Cycloserine; Cognitive Remediation

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; 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; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Limitations and Caveats

Study was terminated early due to PI leaving previous institution. A high number of participants did not complete full duration of study interventions.

Results Point of Contact

• Title: Nicholas Breitborde, PhD
• Organization: The Ohio State University

nicholas.breitborde@osumc.edu

614-685-6052

Study Officials

• Nicholas Breitborde, PhD

  The University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Psychiatry

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: September 4, 2013
• Study Start: March 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: June 16, 2020
• Results First Posted: June 4, 2020

Record last verified: 2020-06

Locations

US (1)