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Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: 1-year Follow-up (PAFIP2_nc1Y)

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ClinicalTrials.gov Identifier: NCT02534363
Recruitment Status : Completed
First Posted : August 27, 2015
Last Update Posted : March 14, 2017
Sponsor:
Collaborators:
Centro de Investigación Biomédica en Red de Salud Mental
Instituto de Investigación Marqués de Valdecilla
Information provided by (Responsible Party):
Benedicto Crespo-Facorro, Fundación Marques de Valdecilla

Brief Summary:
Cognitive enhancement is a primary goal in treating individuals with schizophrenia. Cognitive deficits are already present at the first break of the illness, seem to remain stable during early phases and noticeably influence daily functioning. Differences among antipsychotics in terms of cognitive effectiveness have turned out to be a topic of increasing research interest. The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics (SGAs) compared to first-generation antipsychotics (FGAs) is currently under debate. Long-term studies would be of great value to evaluate the differential benefits exerted by antipsychotic drugs on cognitive performance. The aim of this study is to investigate the cognitive effects of aripiprazole, quetiapine and ziprasidone in first-episode psychosis at 1 year.

Condition or disease Intervention/treatment Phase
Schizophrenia Psychotic Disorders Drug: Aripiprazole Drug: Quetiapine Drug: Ziprasidone Behavioral: Cognitive battery Phase 4

Detailed Description:

Study setting and financial support: data for the present investigation were obtained from an ongoing epidemiological and three-year longitudinal intervention program of first-episode psychosis (PAFIP) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marqués de Valdecilla, Spain. Conforming to international standards for research ethics, this program was approved by the local institutional review board. Patients meeting inclusion criteria and their families provided written informed consent to be included in the PAFIP. The Mental Health Services of Cantabria provided funding for implementing the program. No pharmaceutical company supplied any financial support.

Study design: this is a prospective, randomized, flexible-dose, open-label study. Investigators used a simple randomization procedure: a computer-generated randomization list was drawn up by a statistician. Dose ranges were 5-30 mg/day Aripiprazole, 40-160 mg/day Ziprasidone and 100-600 mg/day Quetiapine. Rapid titration schedule (5-day), until optimal dose was reached, was as a rule used unless severe side effects occur. At the treating physician's discretion, the dose and type of antipsychotic medication could be changed based on clinical efficacy and the profile of side effects during the follow-up period. Antimuscarinic medication, Lormetazepam and Clonazepam were permitted for clinical reasons. No antimuscarinic agents were administered prophylactically. Antidepressants (Sertraline) and mood stabilizers (lithium) were permitted if clinically needed.

Clinical assessment: the severity scale of the Clinical Global Impression (CGI) scale, the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive symptoms (SAPS), the Scale for the Assessment of Negative symptoms (SANS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Young Mania Rating Scale (YMRS) were used to evaluate symptomatology. To assess general adverse event experiences, the Scale of the Udvalg for Kliniske Undersogelser (UKU), the Simpson-Angus Rating Scale (SARS) and the Barnes Akathisia Scale (BAS) were used. The same trained psychiatrist (BC-F) completed all clinical assessments. These clinical data are described at AZQ2005 study.

Neuropsychological assessment. Cognitive functioning was assessed in patients at 2 points: baseline and 1 year after the initialization of antipsychotic treatment. The cognitive assessment at baseline was carried out at 12 weeks after recruitment because this time is considered optimal for patients' stabilization. The evaluation required approximately 2 h and was carried out in the same day by the same neuropsychologist (R.A.-A and E.G.-R). The neuropsychological battery comprises 9 cognitive domains: information processing speed, motor dexterity, working memory, verbal learning, visuospatial abilities, delayed memory, attention, executive function and theory of mind.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: a Randomized Comparison of Aripiprazole, Quetiapine and Ziprasidone Over 1 Year
Actual Study Start Date : October 2005
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2013


Arm Intervention/treatment
Active Comparator: Aripiprazole & cognitive battery
Aripiprazole 5-30 mg/day. Cognitive battery at baseline and at 1 year.
Drug: Aripiprazole
Oral, dose range 5-30 mg/day, once or twice a day, during study duration
Other Name: Abilify

Behavioral: Cognitive battery
Completed in the following standardized sequence: 1-the Rey Auditory Verbal Learning Test (RAVLT); 2-WAIS-III digit symbol subtest; 3-Grooved Pegboard Test; 4-The Zoo Map Test; 5-Tower of London Test (ToL); 6-Rey Complex Figure (RCF); 7-Trail Making Test (TMT); 8-WAIS-III digits forward and backward subtests; 9-WAIS-III letter-number sequencing subtest; 10-WAIS-III vocabulary subtest that was used as measure of premorbid intelligence quotient (IQ); 11-Stroop Test; 12-letter (FAS) and semantic (animal) fluency tests; 14-Eyes Task; 15-Continuous Performance Test (CPT).

Active Comparator: Quetiapine & cognitive battery
Quetiapine 100-600 mg/day. Cognitive battery at baseline and at 1 year.
Drug: Quetiapine
Oral, dose range 100-600 mg/day, once or twice a day, during study duration
Other Name: Seroquel

Behavioral: Cognitive battery
Completed in the following standardized sequence: 1-the Rey Auditory Verbal Learning Test (RAVLT); 2-WAIS-III digit symbol subtest; 3-Grooved Pegboard Test; 4-The Zoo Map Test; 5-Tower of London Test (ToL); 6-Rey Complex Figure (RCF); 7-Trail Making Test (TMT); 8-WAIS-III digits forward and backward subtests; 9-WAIS-III letter-number sequencing subtest; 10-WAIS-III vocabulary subtest that was used as measure of premorbid intelligence quotient (IQ); 11-Stroop Test; 12-letter (FAS) and semantic (animal) fluency tests; 14-Eyes Task; 15-Continuous Performance Test (CPT).

Active Comparator: Ziprasidone & cognitive battery
Ziprasidone 40-160 mg/day. Cognitive battery at baseline and at 1 year.
Drug: Ziprasidone
Oral, dose range 40-160 mg/day, once or twice a day, during study duration
Other Name: Zeldox

Behavioral: Cognitive battery
Completed in the following standardized sequence: 1-the Rey Auditory Verbal Learning Test (RAVLT); 2-WAIS-III digit symbol subtest; 3-Grooved Pegboard Test; 4-The Zoo Map Test; 5-Tower of London Test (ToL); 6-Rey Complex Figure (RCF); 7-Trail Making Test (TMT); 8-WAIS-III digits forward and backward subtests; 9-WAIS-III letter-number sequencing subtest; 10-WAIS-III vocabulary subtest that was used as measure of premorbid intelligence quotient (IQ); 11-Stroop Test; 12-letter (FAS) and semantic (animal) fluency tests; 14-Eyes Task; 15-Continuous Performance Test (CPT).




Primary Outcome Measures :
  1. Global cognitive index [ Time Frame: 1 year ]
    In order to calculate a measure of Global Cognitive Functioning (GCF) raw cognitive scores were reversed when appropriate before standardization so they all have the same direction (the higher, the better). According to previous methodology, the GCF was calculated as T-scores, with raw scores of a healthy comparison sample. T scores were converted to deficit scores that reflect presence and severity of cognitive impairment. Deficit scores on all tests were then "averaged" to create the GCF score.


Secondary Outcome Measures :
  1. Change in information processing speed [ Time Frame: 1 year ]
    Measured by Wechsler Adult Intelligence Scale (WAIS) - III digit symbol subtest (standard total score), Trail Making Test (TMT) trail A and Continuous Performance Test (CPT) reaction time.

  2. Change in motor dexterity [ Time Frame: 1 year ]
    Measured by Grooved Pegboard Test (time to complete with dominant hand).

  3. Change in working memory [ Time Frame: 1 year ]
    Measured by WAIS - III letter-number sequencing test (standard total score) and WAIS - III digits forward (standard total score).

  4. Change in verbal learning [ Time Frame: 1 year ]
    Measured by the Rey Auditory Verbal Learning Test (RAVLT) (trials 1-5).

  5. Change in visuospatial abilities [ Time Frame: 1 year ]
    Measured by the Rey Complex Figure (RCF) (copy figure).

  6. Change in delayed memory [ Time Frame: 1 year ]
    Measured by RAVLT (list recall and list recognition discrimination subscore) and RCF (delayed recall).

  7. Change in attention [ Time Frame: 1 year ]
    Measured by CPT (discrimination subscores).

  8. Change in executive function [ Time Frame: 1 year ]
    Measured by TMT trail B, Stroop Test (color-word), the Zoo Map Test (first and second conditions), the Tower of London Test (ToL) (total correct and total moves score) and letter (FAS) and semantic (animal) fluency tests.

  9. Change in theory of mind [ Time Frame: 1 year ]
    Measured by Eyes Task (total correct score).



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients followed in the First Episode Psychosis Clinical Program (PAFIP II) from October 2005 to January 2011.
  • Experiencing their first episode of psychosis (First Episode of Psychosis is defined as that psychopathological state in which for the first time and regardless of its duration, the patient has enough severe psychotic symptoms to allow a diagnosis of psychosis, having received no specific psychiatric treatment for him).
  • Living in the catchment area (Cantabria).
  • No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.
  • Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or schizoaffective disorder.

Exclusion Criteria:

  • Meeting DSM-IV criteria for drug dependence.
  • Meeting DSM-IV criteria for mental retardation.
  • Having a history of neurological disease or head injury with loss of consciousness.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02534363


Locations
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Spain
University Hospital Marqués de Valdecilla
Santander, Cantabria, Spain, 39008
Sponsors and Collaborators
Fundación Marques de Valdecilla
Centro de Investigación Biomédica en Red de Salud Mental
Instituto de Investigación Marqués de Valdecilla
Investigators
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Principal Investigator: Benedicto Crespo-Facorro, Professor University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Santander, Spain.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Benedicto Crespo-Facorro, Associate Professor of Psychiatry, Fundación Marques de Valdecilla
ClinicalTrials.gov Identifier: NCT02534363    
Other Study ID Numbers: AZQ2005_nc1Y
CI 2005-0308007 ( Other Grant/Funding Number: SENY Fundació Research Grant CI 2005-0308007 )
First Posted: August 27, 2015    Key Record Dates
Last Update Posted: March 14, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Benedicto Crespo-Facorro, Fundación Marques de Valdecilla:
Cognition
Psychosis
Antipsychotic Agents
Treatment
Effectiveness
Aripiprazole
Quetiapine
Ziprasidone
Neurocognition
Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Aripiprazole
Quetiapine Fumarate
Ziprasidone
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Dopamine D2 Receptor Antagonists
Dopamine Antagonists