Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: 3-years Follow-up (PAFIP3_nc3Y)

• ClinicalTrials.gov Identifier: NCT03883204
• Recruitment Status: Unknown
• First Posted: March 20, 2019
• Last Update Posted: January 14, 2020
• Sponsor: Fundación Marques de Valdecilla
• 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

Study Description

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 and risperidone in first-episode psychosis at 3 years.

Condition or disease	Intervention/treatment	Phase
Schizophrenia; Psychotic Disorders; Psychosis	Drug: Aripiprazole; Drug: Risperidone	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 flexible-dose study of two neuroleptics (Aripiprazole and Risperidone) assigned at aleatory ratio 1:1. Rapid titration schedule (5-day), until optimal dose is reached, is 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 are allowed for clinical reasons. No antimuscarinic agents are administered prophylactically. Antidepressants (Sertraline) and mood stabilizers (lithium) are 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 3 years 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 115 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 and Risperidone Over 3 Years
• Actual Study Start Date: January 1, 2015
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Aripiprazole; Oral, dose range 10-30 mg/day, once or twice a day during study duration.	Drug: Aripiprazole; Initial dose: 10 mg.; Other Name: Abilify
Active Comparator: Risperidone; Oral, dose range 1-6 mg/day, once or twice a day during study duration.	Drug: Risperidone; Initial dose: 2 mg.; Other Name: Risperdal

Outcome Measures

Primary Outcome Measures :

1. Global cognitive index [ Time Frame: 3 years ]
   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: 3 years ]
   Measured by Wechsler Adult Intelligence Scale (WAIS)-III digit symbol subtest (standard total score).
2. Change in information processing speed [ Time Frame: 3 years ]
   Measured by Trail Making Test (TMT) trail A.
3. Change in information processing speed [ Time Frame: 3 years ]
   Measured by Continuoys Performace Test (CPT) reaction time.
4. Change in motor dexterity [ Time Frame: 3 years ]
   Measured by Grooved Pegboard Test (time to complete with dominant hand).
5. Change in working memory [ Time Frame: 3 years ]
   Measured by WAIS-III letter-number sequencing test (standard total score).
6. Change in working memory [ Time Frame: 3 years ]
   Measured by WAIS-III digits forward (standard total score).
7. Change in verbal learning [ Time Frame: 3 years ]
   Measured by the Rey Auditory Verbal Learning Test (RAVLT) (trials 1-5).
8. Change in visuospatial abilities [ Time Frame: 3 years ]
   Measured by the Rey Complex Figure (RCF) (copy figure).
9. Change in delayed memory [ Time Frame: 3 years ]
   Measured by the Rey Auditory Verbal Learning Test (RAVLT) (list recall and list recognition discrimination subscore).
10. Change in delayed memory [ Time Frame: 3 years ]
    Measured by the Rey Complex Figure (RCF) (delayed recall).
11. Change in attention [ Time Frame: 3 years ]
    Measured by Continuoys Performace Test (CPT) (discrimination subscores).
12. Change in executive function [ Time Frame: 3 years ]
    Measured by Trail Making Test (TMT) trail B.
13. Change in executive function [ Time Frame: 3 years ]
    Measured by Stroop Test (color-word).
14. Change in executive function [ Time Frame: 3 years ]
    Measured by the Zoo Map Test (first and second conditions).
15. Change in executive function [ Time Frame: 3 years ]
    Measured by the Tower of London Test (ToL) (total correct and total moves score).
16. Change in executive function [ Time Frame: 3 years ]
    Measured by FAS Word Fluency and semantic (animal) fluency tests.
17. Change in theory of mind [ Time Frame: 3 years ]
    Measured by Eyes Task (total correct score).

Eligibility Criteria

• 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 III) from January 2015 to December 2020.
• 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.

Contacts and Locations

Locations

Spain

University Hospital Marques 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

• 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.

More Information

• Responsible Party: Benedicto Crespo-Facorro, Professor of Psychiatry, Fundación Marques de Valdecilla
• ClinicalTrials.gov Identifier: NCT03883204
• Other Study ID Numbers: ROAC2018_nc3Y
• First Posted: March 20, 2019
• Last Update Posted: January 14, 2020
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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; Antipsychotic Agents; Treatment; Effectiveness; Aripiprazole; Risperidone

Additional relevant MeSH terms:

Schizophrenia; Psychotic Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Risperidone; Aripiprazole; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents; Antidepressive Agents; Dopamine Agonists; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Dopamine D2 Receptor Antagonists