Efficacy of Cognitive Remediation in Patients With Schizophrenia or Schizoaffective Disorder Stabilized on Lurasidone
Condition: Schizophrenia
MeSH terms: Schizophrenia; Psychotic Disorders
Intervention: Cognitive Remediation
Intervention description: Cognitive remediation intervention will be administered in small group settings twice weekly for 30 sessions and will utilize computerized and verbal group training exercises to address basic skills such as auditory processing, attention, processing speed, and verbal working memory and learning, as well as intermediate and complex skills such as deductive reasoning, planning and sequencing, set shifting, and complex problem solving.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Cognition; Function; Attention; Vigilance; Verbal Memory; Visual Memory; Processing Speed; Problem Solving; Social Cognition

Summary:

      The investigators hypothesize that cognitive remediation will be superior to the active
      control group on the change from baseline to study end point of cognitive remediation phase
      on both co-primary outcome measures (standardized composite MATRICS score and Cognitive
      Assessment Interview).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between 18-55 years of age who meet DSM-IV-TR criteria for
             schizophrenia or schizoaffective disorder confirmed by the Structured Clinical
             Interview for DSM-IV Clinical trial version (SCID-CT version). Duration of illness > 1
             year. Outpatient status.

          -  Change in antipsychotic medication is clinically warranted as evidenced by

               -  persistent psychosis despite adequate dose and duration of antipsychotic, or *
                  inability to achieve therapeutic dose because of dose-limiting side effects,

               -  persistent side effects that either cause significant subjective distress or
                  significantly increase medical risks, such as substantial weight gain or
                  metabolic disturbances, or

               -  patient preference to switch and treating psychiatrist is in agreement.

          -  No behaviors suggesting potential danger to self or others over the 6 months prior to
             participation.

          -  For the last 2 weeks of lurasidone stabilization phase, a score of 4 or less on PANSS
             items of conceptual disorganization, hallucinations, suspiciousness and unusual
             thought content items.

          -  At end of lurasidone stabilization phase, Simpson-Angus Scale total score <

          -  At end of lurasidone stabilization phase, Calgary Depression Scale total score <10.

          -  No acute medical problems; any chronic medical condition (e.g. hypertension)
             consistently treated and stable during the 1 month prior to participation.

          -  Able to provide signed informed consent and to cooperate with all study procedures.

          -  Able to attend twice weekly sessions (each lasting approximately 75 minutes) for
             cognitive remediation or active control sessions for the ~6 month duration of the
             cognitive remediation phase of the study.

          -  Must meet the following cognitive performance criteria:

               -  Able to complete the baseline MATRICS validly at baseline as assessed by NP
                  tester.

               -  Raw score of 12 or greater on the WTAR (Wechsler Test of Adult Reading) at
                  screening.

          -  Women who can become pregnant must be using an adequate method of contraception to
             avoid pregnancy throughout the study and for up to 4 weeks after the study in such a
             manner that the risk of pregnancy is minimized. Acceptable methods include oral,
             injectable or implanted contraceptives, intrauterine devices or barrier methods such
             as condoms, diaphragm and spermicides. Women who can become pregnant must have a
             negative urine pregnancy test at the Screening Visit. Women who can become pregnant
             include anyone who has experienced menarche and who has not undergone successful
             surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral
             oophorectomy), or is not postmenopausal (defined as amenorrhea 12 consecutive months).

        Exclusion Criteria:

          -  Documented history of learning disability.

          -  Hearing or visual impairment; not fluent in English.

          -  Current treatment with clozapine or history of treatment resistance as evidenced by
             failure to improve (in the judgment of the investigator) with 2 or more adequate dose
             antipsychotic trials of at least 6 weeks duration in preceding 1 year.

          -  Concomitant or anticipated treatment with potent CYP 3A4 inhibitor such a cimetidine,
             cyclosporine, erythromycin or erythromycin-like drugs (e.g., azithromycin,
             clarithromycin except short term acute treatment for 1 week or less), diltiazem,
             itraconazole, ketoconazole or other systemic antifungal agents in the azole class,
             nefazodone; or potent CYP3A4 inducer including: carbamazepine, modafinil,
             Phenobarbital, phenytoin, rifampin, St. Johns Wort, and troglitazone.

          -  Current treatment with psychotropic agents known to affect cognition such as
             amphetamines, topiramate.

          -  History of treatment with electroconvulsive therapy within the 6 months prior to
             participation or expectation that patient may require ECT during the study.

          -  History of neurological or neuropsychiatric conditions (e.g. stroke, traumatic brain
             injury, epilepsy, etc).

          -  Subjects with a history of clinically significant neurological, metabolic, hepatic,
             renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological
             disorders (e.g. unstable angina, decompensate congestive heart failure, CNS infection
             or history of HIV seropositivity), which would pose a risk to the patient if they were
             to participate in the study or that might confound the results of the study. Active
             medical conditions that are minor or well controlled are not exclusionary if they do
             not affect risk to the patient of the study results. For example, the following are
             not exclusionary: a) stable and well-controlled hypertension; b) asthma (no serious
             attacks in the past year); c) hypothyroidism (TSH within normal limits).

          -  A positive test for Hepatitis C antibody with concurrent evidence of impaired hepatic
             function (increased AST or ALT greater than 2 times the upper limit of normal) or
             positive tests for Hepatitis A antibody IgM fraction or Hepatitis B surface antigen,
             irrespective of the AST or ALT values.

          -  History of alcohol or substance abuse or dependence during the 6 months prior to
             participation.

          -  Participation in a clinical trial involving an investigational medication within 3
             months prior to participation or 2 or more investigational drug trials in the
             preceding 12 months.

          -  Pregnant women or women of child-bearing potential who are not using adequate birth
             control.

          -  Woman who are breast feeding.

          -  Individuals who: a) received any cognitive remediation in the 6 months prior to study
             entry or b)received more than 6 hours of cognitive remediation in the 12 months prior
             to study entry or c) received more than 15 hours in the 24 months prior to study
             entry. Cognitive remediation is defined as any behavioral intervention consisting of
             training activities that aim to target impairments in cognitive domains of sensory
             processing, attention, memory, processing speed, working memory, and executive
             functioning.