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SchizophreniaPhase 3NCT01173874

Efficacy of Cognitive Remediation in Patients With Schizophrenia or Schizoaffective Disorder Stabilized on Lurasidone

A Phase 3 study testing Cognitive Remediation in people with Schizophrenia, run by New York State Psychiatric Institute at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Schizophrenia
What is being tested?
Cognitive Remediation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
16 sitesUnited States
Study dates
Jul 2010to Nov 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
Show all 16Show fewer
  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • Medical College of Georgia

    Augusta, Georgia, 30912

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Duke University Medical Center

    Butner, North Carolina, 27509

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Psychiatric Clinical Research Center

    Chicago, Illinois, 60612

  • University of Missouri

    Columbia, Missouri, 65212

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • San Fernando Mental Health Center

    Granada Hills, California, 91344

  • Indiana University

    Indianapolis, Indiana, 46222

  • University of Miami Department of Psychiatry

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55454

  • Yale University

    New Haven, Connecticut, 06519

  • Columbia University

    New York, New York, 10032

  • Psychopharmacology Research Unit- Nathan KIine Institute for Psychiatric Research

    New York, New York, 10035

  • University of California - Irvine

    Orange, California, 92868

  • University of Texas Health Science Center, San Antonio

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Clinical and Biomarker Assessment of Efficacy of Cognitive Remediation in Patients With Schizophrenia or Schizoaffective Disorder Stabilized on Lurasidone

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).

Read the detailed description

OVERVIEW \& SPECIFIC AIMS Marked cognitive impairment underlies much of the social \& occupational dysfunction associated with schizophrenia. Currently available antipsychotic medications are primarily effective in treating psychotic symptoms \& have demonstrated only limited potential in ameliorating cognitive deficits in schizophrenia patients.

Lurasidone is a novel compound synthesized by SEPRACOR, Inc.for the treatment of patients with schizophrenia \& bipolar disorder. It possesses high affinity for dopamine D2, serotonin 5-HT2A, 5-HT7, 5-HT1A \& noradrenaline α2C receptors. Compared with other atypical antipsychotics, lurasidone demonstrates similar binding affinities for the D2 \& 5-HT2A receptors, but greater affinity for serotonin 5-HT1A receptors. Lurasidone displays no affinity for histamine H1 or acetylcholine M1 receptors. In animal studies, lurasidone significantly reversed memory impairment induced by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, in a rat step-through type passive avoidance task. The maximum inhibitory effects of lurasidone were greater than those observed with risperidone, quetiapine, \& olanzapine, while aripiprazole was not effective in reversing the impairment induced by MK-801. Additionally, lurasidone significantly reversed memory impairment induced by the anticholinergic drug scopolamine in the passive avoidance task. The reversal of pharmacologically induced cognitive deficits in rats by lurasidone is promising \& warrants specific investigation in subjects with schizophrenia, given the prominence of cognitive deficits in this disorder.

From a different therapeutic perspective, the utility of cognitive remediation in ameliorating cognitive deficits \& improving functional outcomes in schizophrenia has recently been evaluated in several studies. A meta-analysis of these trials found effect sizes for improvement in cognitive \& psychosocial functioning in the low to moderate range (McGurck 2007). The best outcomes in psychosocial functioning were evident when cognitive remediation was combined with teaching of psychosocial skills.

Given the recalcitrant nature of cognitive deficits in schizophrenia \& their impact on functional capacity we felt that in designing a study to test the effectiveness of cognitive remediation we should maximize the likelihood of therapeutic benefit by administering cognitive remediation in the context of pharmacotherapy that may have potential for precognitive effects. By so doing we could possibly boost the effect sizes seen with cognitive remediation alone. In this study we will transition patients with schizophrenia (in whom a change in antipsychotic therapy is clinically warranted) from their current antipsychotic to lurasidone - clinicians will have eight weeks to complete the switch. Subjects who are successfully switched to lurasidone will then be randomized to receive either cognitive remediation or a non-specific mental activity control condition two times/week for a total of 30 sessions over a 4-6 month period. Our goal is to have 140 patients complete the cognitive remediation phase.

A subset of the sample will participate in 2 biomarker studies. Event related potentials \& fMRI will be done in these subjects at baseline \& study completion.

This study will be done as an Investigator initiated trial (J. Lieberman, M.D. - PI) under a separate IND.

Primary Aim: We 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 \& Cognitive Assessment Interview).

Additional aims

  1. To compare cognitive remediation to active control on functional outcome as assessed by the change in UCSD Performance-Based Skills Assessment (UPSA-Brief) from baseline to end point of cognitive remediation phase.
  2. To compare cognitive remediation to active control on changes from lurasidone stabilized baseline to end point in indices of functional brain activation (ERP \& fMRI) during cognitive activation tasks.
  3. Evaluate the effect of 8 weeks of lurasidone treatment on cognitive \& functional outcomes as assessed by changes from baseline in the MATRICS composite score, CAI, \& UPSA-Brief.
  4. Evaluate the effect of cognitive remediation compared to nonspecific mental activity on cognitive \& functional outcomes as assessed by changes from lurasidone stabilized baseline to end of cognitive remediation phase in the MATRICS composite score, CAI, \& UPSA-Brief.
  5. Evaluate the efficacy, safety, \& tolerability of lurasidone in patients with schizophrenia as assessed by the change from baseline to week 8 \& to end of cognitive remediation phase in the PANSS total score, Side Effect Checklist, AIMS, SAS, BAS, \& frequency of abnormal laboratory values.
Conditions
Schizophrenia
Being tested
Cognitive Remediation
Keywords
Cognition, Function, Attention, Vigilance, Verbal Memory, Visual Memory, Processing Speed, Problem Solving, Social Cognition
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cognitive RemediationDrug

    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.

Study groups in NCT01173874
Study groupRoleWhat they receive
Cognitive RemediationExperimentalCognitive 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.
Receives: Drug: Cognitive Remediation
Cognitive activity control groupNo interventionThis is a non-specific mental activity control condition, conducted two times per week for a total of 30 sessions.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cognitive Function Measured by MCCB Composite Score

    The MATRICS Consensus Cognitive Battery (MCCB) will be used to assess cognitive function. The MCCB composite score is comprised of sub-scale measures of: a) working memory; b) attention and vigilance; c) verbal learning; d) visual learning; e) speed of processing; f) reason and problem solving; and g) social cognition. The MCCB takes 90 minutes or less to complete.

    MCCB assessed 4 times: prestabilization (screening), randomization (after 6-8 weeks of lurasidone stabilization, prior to initial cognitive remediation), midpoint (after 20 cognitive remediation session), and study completion (final visit after 30 cognitive remediation sessions).

    MCCB composite scores are reported as t-scores where a t-score = 50 is the population average. Every 10 points is one standard deviation. There is no range as scores are as far from population average.

    Measured: 4-6 month period

  2. Cognitive Function as Measured by the University of California, San Diego, Performance-Based Skills Assessment-Brief (UPSA-B) Scale

    The UPSA-B assesses functional capacity to perform tasks similar to those in daily life. Raw scores are converted into scaled scores ranging from 0-100, with higher scores indicating better functional capacity.

    Measured: 4-6 month period

Secondary outcomes (2)

  1. Cognition as Measured by Cognitive Assessment Interview (CAI)

    Cognitive Assessment Interview was used to obtain information about cognitive functioning from both subject and an informant. Composite CAI scores were reported. Scale ranges from 1-7 with the following anchors:

    1. Normal, no cognitive impairment
    2. Borderline impairment
    3. Mildly impaired
    4. Moderately impaired
    5. Markedly impaired
    6. Severely impaired
    7. Among the most extremely impaired

    Measured: 4-6 month period

  2. Efficacy as Measured by Positive and Negative Syndrome Scale (PANSS)

    Total PANSS score with 30 items. Each item is rated 1-7 so the minimum Total PANSS score =30 and the maximum is 210. Anchors for each item are as follows, the higher values represent an increase in severity of symptoms:

    1. Absent
    2. Minimal
    3. Mild
    4. Moderate
    5. Moderately severe
    6. Severe
    7. Extremely severe

    Measured: 4-6 month period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionOct 2013
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01173874
Sponsor's protocol ID
#6121
Status last verified
Feb 2017
First submitted
8 Jul 2010
Last updated
11 Apr 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Baddeley A. Working memory. Science. 1992 Jan 31;255(5044):556-9. doi: 10.1126/science.1736359.

    PubMed 1736359

  • Bruder GE, Wexler BE, Sage MM, Gil RB, Gorman JM. Verbal memory in schizophrenia: additional evidence of subtypes having different cognitive deficits. Schizophr Res. 2004 Jun 1;68(2-3):137-47. doi: 10.1016/S0920-9964(03)00156-7.

    PubMed 15099598

  • Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD. Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 1998 Sep;155(9):1285-7. doi: 10.1176/ajp.155.9.1285.

    PubMed 9734557

  • Davidson M, Galderisi S, Weiser M, Werbeloff N, Fleischhacker WW, Keefe RS, Boter H, Keet IP, Prelipceanu D, Rybakowski JK, Libiger J, Hummer M, Dollfus S, Lopez-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rossler A, Kahn RS. Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry. 2009 Jun;166(6):675-82. doi: 10.1176/appi.ajp.2008.08060806. Epub 2009 Apr 15.

    PubMed 19369319

  • Elger CE, Grunwald T, Lehnertz K, Kutas M, Helmstaedter C, Brockhaus A, Van Roost D, Heinze HJ. Human temporal lobe potentials in verbal learning and memory processes. Neuropsychologia. 1997 May;35(5):657-67. doi: 10.1016/s0028-3932(96)00110-8.

    PubMed 9153028

  • Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. Am J Psychiatry. 2009 Jul;166(7):805-11. doi: 10.1176/appi.ajp.2009.08050757. Epub 2009 May 15.

    PubMed 19448187

  • Goldman-Rakic PS. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry. 1999 Sep 1;46(5):650-61. doi: 10.1016/s0006-3223(99)00130-4.

    PubMed 10472417

  • Goldman-Rakic PS. Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci. 1994 Fall;6(4):348-57. doi: 10.1176/jnp.6.4.348.

    PubMed 7841806

  • Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res. 2004 Dec 15;72(1):41-51. doi: 10.1016/j.schres.2004.09.009.

    PubMed 15531406

  • Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. doi: 10.1176/ajp.153.3.321.

    PubMed 8610818

  • Gur RE, Jaggi JL, Shtasel DL, Ragland JD, Gur RC. Cerebral blood flow in schizophrenia: effects of memory processing on regional activation. Biol Psychiatry. 1994 Jan 1;35(1):3-15. doi: 10.1016/0006-3223(94)91160-6.

    PubMed 8167200

  • Kayser J, Bruder GE, Friedman D, Tenke CE, Amador XF, Clark SC, Malaspina D, Gorman JM. Brain event-related potentials (ERPs) in schizophrenia during a word recognition memory task. Int J Psychophysiol. 1999 Dec;34(3):249-65. doi: 10.1016/s0167-8760(99)00082-3.

    PubMed 10610049

  • Kayser J, Tenke CE. Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: I. Evaluation with auditory oddball tasks. Clin Neurophysiol. 2006 Feb;117(2):348-68. doi: 10.1016/j.clinph.2005.08.034. Epub 2005 Dec 13.

    PubMed 16356767

  • Kayser J, Tenke CE. Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: II. Adequacy of low-density estimates. Clin Neurophysiol. 2006 Feb;117(2):369-80. doi: 10.1016/j.clinph.2005.08.033. Epub 2005 Dec 13.

    PubMed 16356768

  • Kayser J, Tenke CE, Gates NA, Kroppmann CJ, Gil RB, Bruder GE. ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia. Psychophysiology. 2006 May;43(3):237-52. doi: 10.1111/j.1469-8986.2006.00398.x.

    PubMed 16805862

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cognitive Remediation in people with Schizophrenia, run by New York State Psychiatric Institute at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cognitive Function Measured by MCCB Composite Score (time frame: 4-6 month period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01173874, which also lists 40 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2017.

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