Effects of Risperdal Consta on Ability to Benefit From Social Skills Training in Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      The specific aim of this study is to determine whether the new, long-acting, form of
      risperidone, Risperdal Consta, improves the ability of schizophrenia patients to benefit from
      skills training. The hypothesis guiding this study is that Risperdal Consta, by improving
      verbal memory, will improve the ability to benefit from skills training interventions among
      schizophrenia patients. The primary objective of this study is to compare patients on
      Risperdal Consta to patients on other atypical antipsychotic medications in terms of their
      ability to benefit from skills training interventions. A secondary objective of this study is
      to determine whether patients taking Risperdal Consta improve in other areas of cognitive
      functioning and social functioning.
    

Detailed description: 
      The study will be conducted at the University of Illinois at Chicago and New York
      Presbyterian Hospital-Westchester Division. Patients with schizophrenia or schizoaffective
      disorder who are considered by their clinicians to not be clinically stable, or to be stable
      but still symptomatic, will be referred to the study. After obtaining informed consent,
      patients will be randomized either to the Risperdal Consta or control conditions. Patients in
      the control condition will remain on their oral antipsychotic medication for the duration of
      the study (note - patients currently taking oral risperidone will not be eligible for the
      study). Patients randomized to the Consta condition will take oral risperidone for 3 days,
      and if there are no adverse effects, they will begin receiving injections of Consta every 2
      weeks over the next 6 months. During the first month, they will remain on oral risperidone,
      which will be tapered by the end of the month along with other antipsychotic medications
      other than Consta. At baseline, and every 4 weeks for 6 months, all patients will complete a
      computerized cognitive testing battery (CogTest), and be interviewed about social functioning
      and symptomatology. During months 4-6 of study participation, all patients will participate
      in a social skills group, the UCLA Basic Conversation Skills Module. Before and after this
      group, patients will be interviewed and participate in role-play based assessments regarding
      skills to be taught in the group. Patients will also receive physical exams, including and
      ECG, at baseline, and be monitored for side effects and adverse events every 2 weeks. The
      hypothesis driving this study is that patients in the Consta group will demonstrate greater
      improvement in verbal learning, skill acquisition in the training group, and improved social
      functioning, over the course of the 6 months. This hypothesis is based on prior data
      demonstrating that oral risperidone improves verbal memory, which is a mediator of skill
      acquisition in structured skills training groups. If this hypothesis is supported, it would
      be an important demonstration that a novel medication preparation (injectable Risperdal
      Consta) can, when combined with psychiatric rehabilitation, improve functional outcomes for
      patients participating in rehabilitation.

      Efficacy Measures:

        1. The primary efficacy measure for this study will be the Micro-Module Learning Tests
           (MMLT) (Silverstein et al., in press). This is a set of 7 psychometrically equivalent
           tests that assess responsiveness to the key components of skills training. Each test has
           3 parts: 1) a verbal learning component wherein the patient is read material from an
           actual skills training group and then asked questions about the material; 2) a modeling
           component in which the patient views a model performing a specific behavior on a
           videotape, and is then asked questions about what was viewed; and 3) a role-play
           component in which the patient is asked to demonstrate, via a role-play, the behavior
           that the model demonstrated in the prior section. The MMLT is a dynamic assessment
           measure in that, in addition to measuring what people can recall/perform after an
           initial presentation of information, it allows for a determination of learning potential
           after repeated exposure to the information. With the MMLT, each time a question is
           initially answered incorrectly, a briefer version of the material, that highlights the
           most relevant information is presented. If an incorrect answer is given at this point,
           an even more focused version of the item is presented. With this scoring system,
           responsiveness to skills training as it occurs in the real world (where repetition of
           material is built into the teaching method) can be assessed more accurately than when
           using a static assessment (where information is only presented once).

        2. A second primary efficacy measure will be the Comprehensive Module Test for the Basic
           Conversation Skills Module. This measure is administered before and after the group.

        3. A secondary efficacy measure is the CogTest computerized cognitive battery. This battery
           was developed by Tonmoy Sharma, M.D. and colleagues, and has been used with over 2000
           schizophrenia patients in studies of risperidone or Consta to date.

        4. Another secondary efficacy measure is the Social Functioning Scale (SFS) (Birchwood et
           al., 1990). This is a 74 item scale that is rated by the patient. The SFS has seven
           subscales: 1) social engagement/withdrawal; 2) interpersonal communication; 3)
           independence-performance of activities of daily living; 4) independence-competence to
           perform activities of daily living; 5) frequency of engagement in recreational
           activities; 6) frequency of participation in social activities; and 7) employment.

        5. A third secondary efficacy measure will be the observational measure of attentiveness in
           groups that was developed as part of the PI's current NIMH grant on cognitive
           rehabilitation in schizophrenia. This measure will allow us to determine: 1) if
           Risperdal Consta is improving a real-world measure of attention; and 2) whether there
           are any relationships between skill acquisition, medication, and attention.

        6. The final efficacy measure will be the Positive and Negative Syndrome Scale, which will
           be used to measure symptoms.

      Adverse Events: Side effects and adverse events will be assessed using a semi-structured
      interview given by a research nurse or psychiatrist. There are 40 specific side effects in 6
      categories (general, neurological, cardiovascular, autonomic, urologic, muscular skeletal).
      Adverse events will be rated on an intensity scale of 0 to 4 and a relationship to medication
      of 0 to 5. Side effects will be counted as adverse events for scores of 3 or 4 on intensity
      (moderate or severe) and scores of 3-5 for relationship (possible to definite). These adverse
      events will then be aggregated into one of the 6 groups for analysis across groups.

      Serious adverse events will include those that require medical intervention such as
      additional monitoring by the subject's primary physician or medical hospitalization. All
      significant adverse events (such as those listed above or any side effect with an intensity
      level of 4) will be reviewed with the treating psychiatrist and the independent medical
      reviewers. Each site will have two independent medical reviewers (one internist, one
      psychiatrist) to examine any serious or significant adverse events and determine if the
      subject should be withdrawn from the study. The two reviewers will not be directly connected
      to the research group and will not be investigators in the protocol.

      In addition to the assessment of side effects, other scales will be used to measure side
      effects commonly associated with antipsychotic medications. Each month, a blinded research
      assistant will perform an Abnormal Involuntary Movement Scale (AIMS, to assess for tardive
      dyskinesia), Barnes Akathisia Scale, and Simpson-Angus Scale (to assess for dystonia and
      parkinsonian side effects). Movement disorders can affect the ability of patients to perform
      on cognitive tests and in skills training groups. Patients with akathisia often have reduced
      attention and reduced ability to concentrate in groups. Patients with parkinsonian symptoms
      can be slower on manual tasks and may have slower mental abilities.

      Laboratory Assessment (to be done at baseline and last month of participation):

        1. Complete Blood Count (CBC) to determine major hematological indices as some
           antipsychotic medications affect the white count.

        2. Complete Chemistries including electrolytes, BUN, creatinine, liver function tests, and
           glucose. Some antipsychotic medications may increase the risk of diabetes and some
           medications may cause an increase in liver enzymes.

        3. Lipid profile including cholesterol, triglycerides, LDL, and HDL. Some antipsychotic
           medications cause an increase in lipids particularly triglycerides

        4. Prolactin: some antipsychotics may increase prolactin leading to menstrual
           irregularities, sexual dysfunction, and possibly osteoporosis. Months 0, 3, 6, only.

        5. Thyroid stimulating hormone (TSH): thyroid functioning can affect cognition. Patients
           with a history of hypothyroidism will be allowed in the study if they are on stable dose
           of replacement and the TSH is in the normal range. Months 0, 3, 6, only.

        6. Glycohemoglobin (HgA1c): to measure the overall level of glucose over the prior 2-3
           months. Months 0, 3, 6, only.

      Laboratory Assessment (monthly)

      1. For women of childbearing potential, urine screen for pregnancy.
    

Intervention name(s): Risperdal Consta (drug); Social Skills Training
Intervention type(s): Drug; Behavioral
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single
Primary purpose: Treatment
Keywords: Schizophrenia; Cognition; Clinical Trial