Clinical trial NCT01934972: A Randomized Controlled Trial of Cognitive Remediation and D-cycloserine for Individuals With Bipolar Disorder
Official title: A Randomized Controlled Trial of Cognitive Remediation and D-cycloserine for Individuals With Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Keywords: Bipolar disorder
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2013-09-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Change From Baseline in Cognitive Functioning
timeFrame: 26 weeks
Secondary outcomes:
measure: Change From Baseline in Manic Symptomatology
timeFrame: 26 weeks
measure: Change From Baseline in Depressive Symptomatology
timeFrame: 26 Weeks
measure: Change From Baseline in Social Functioning
timeFrame: 26 Weeks
measure: Change From Baseline in Functional Capacity
timeFrame: 26 Weeks
Other outcomes:
measure: Change From Baseline in Health-related Quality of Life
timeFrame: 26 weeks
measure: Change From Baseline in Medication Adherence
timeFrame: 26 Weeks
measure: Change From Baseline in Quality of Life
timeFrame: 26 Weeks
measure: Change From Baseline in Stage of Recovery
timeFrame: 26 weeks
measure: Change From Baseline in Metacognition
timeFrame: 26 weeks
measure: Change in Instrinsic Motivation From Baseline
timeFrame: 26 weeks
measure: Frequency of Side Effects During Study Participation
timeFrame: 26 Weeks
Locations:
city: Tucson
country: United States
facility: University of Arizona Medical Center South Campus
state: Arizona
Study officials:
affiliation: The University of Arizona
name: Nicholas Breitborde, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.