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SchizophreniaPhase 4PAFIP2_nc1YNCT02534363

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

A Phase 4 study testing Aripiprazole, Quetiapine and Ziprasidone in people with Schizophrenia and Psychotic Disorders, run by Fundación Marques de Valdecilla at 1 site in Spain.

Completed

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

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 15 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Schizophrenia, Psychotic Disorders
What is being tested?
Aripiprazole, Quetiapine and Ziprasidone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
1 siteSpain
Study dates
Oct 2005to Jan 2013
Phase
Phase 4
Are there results?
None posted in the registry

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 15 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • University Hospital Marqués de Valdecilla

    Santander, Cantabria, 39008

Other trials in Spain

About this study

Official title: Neurocognitive Effectiveness in Treatment of First-episode Non-affective Psychosis: a Randomized Comparison of Aripiprazole, Quetiapine and Ziprasidone Over 1 Year

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.

Read the 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.

Being tested
Aripiprazole, Quetiapine, Ziprasidone, Cognitive battery
Keywords
Cognition, Psychosis, Antipsychotic Agents, Treatment, Effectiveness, Aripiprazole, Quetiapine, Ziprasidone, Neurocognition
Medical subject headings
Schizophrenia, Psychotic Disorders

What participants receive

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

  • AripiprazoleDrug

    Also called Abilify

    Oral, dose range 5-30 mg/day, once or twice a day, during study duration

  • QuetiapineDrug

    Also called Seroquel

    Oral, dose range 100-600 mg/day, once or twice a day, during study duration

  • ZiprasidoneDrug

    Also called Zeldox

    Oral, dose range 40-160 mg/day, once or twice a day, during study duration

  • Cognitive batteryBehavioural

    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).

Study groups in NCT02534363
Study groupRoleWhat they receive
Aripiprazole & cognitive batteryActive comparatorAripiprazole 5-30 mg/day. Cognitive battery at baseline and at 1 year.
Receives: Drug: Aripiprazole; Behavioral: Cognitive battery
Quetiapine & cognitive batteryActive comparatorQuetiapine 100-600 mg/day. Cognitive battery at baseline and at 1 year.
Receives: Drug: Quetiapine; Behavioral: Cognitive battery
Ziprasidone & cognitive batteryActive comparatorZiprasidone 40-160 mg/day. Cognitive battery at baseline and at 1 year.
Receives: Drug: Ziprasidone; Behavioral: Cognitive battery

What is being measured

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

  1. Global cognitive index

    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.

    Measured: 1 year

Secondary outcomes (9)

  1. Change in information processing speed

    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.

    Measured: 1 year

  2. Change in motor dexterity

    Measured by Grooved Pegboard Test (time to complete with dominant hand).

    Measured: 1 year

  3. Change in working memory

    Measured by WAIS - III letter-number sequencing test (standard total score) and WAIS - III digits forward (standard total score).

    Measured: 1 year

  4. Change in verbal learning

    Measured by the Rey Auditory Verbal Learning Test (RAVLT) (trials 1-5).

    Measured: 1 year

  5. Change in visuospatial abilities

    Measured by the Rey Complex Figure (RCF) (copy figure).

    Measured: 1 year

  6. Change in delayed memory

    Measured by RAVLT (list recall and list recognition discrimination subscore) and RCF (delayed recall).

    Measured: 1 year

  7. Change in attention

    Measured by CPT (discrimination subscores).

    Measured: 1 year

  8. Change in executive function

    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.

    Measured: 1 year

  9. Change in theory of mind

    Measured by Eyes Task (total correct score).

    Measured: 1 year

Timeline

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

  1. First posted27 Aug 2015 (estimated)
  2. Study startOct 2005
  3. Primary completionJan 2011
  4. Study completionJan 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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02534363
Sponsor's protocol ID
AZQ2005_nc1Y
Other IDs
CI 2005-0308007
Acronym
PAFIP2_nc1Y
Status last verified
Mar 2017
First submitted
24 Aug 2015
Last updated
14 Mar 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brouwer RM, Klein M, Grasby KL, Schnack HG, Jahanshad N, Teeuw J, Thomopoulos SI, Sprooten E, Franz CE, Gogtay N, Kremen WS, Panizzon MS, Olde Loohuis LM, Whelan CD, Aghajani M, Alloza C, Alnaes D, Artiges E, Ayesa-Arriola R, Barker GJ, Bastin ME, Blok E, Boen E, Breukelaar IA, Bright JK, Buimer EEL, Bulow R, Cannon DM, Ciufolini S, Crossley NA, Damatac CG, Dazzan P, de Mol CL, de Zwarte SMC, Desrivieres S, Diaz-Caneja CM, Doan NT, Dohm K, Frohner JH, Goltermann J, Grigis A, Grotegerd D, Han LKM, Harris MA, Hartman CA, Heany SJ, Heindel W, Heslenfeld DJ, Hohmann S, Ittermann B, Jansen PR, Janssen J, Jia T, Jiang J, Jockwitz C, Karali T, Keeser D, Koevoets MGJC, Lenroot RK, Malchow B, Mandl RCW, Medel V, Meinert S, Morgan CA, Muhleisen TW, Nabulsi L, Opel N, de la Foz VO, Overs BJ, Paillere Martinot ML, Redlich R, Marques TR, Repple J, Roberts G, Roshchupkin GV, Setiaman N, Shumskaya E, Stein F, Sudre G, Takahashi S, Thalamuthu A, Tordesillas-Gutierrez D, van der Lugt A, van Haren NEM, Wardlaw JM, Wen W, Westeneng HJ, Wittfeld K, Zhu AH, Zugman A, Armstrong NJ, Bonfiglio G, Bralten J, Dalvie S, Davies G, Di Forti M, Ding L, Donohoe G, Forstner AJ, Gonzalez-Penas J, Guimaraes JPOFT, Homuth G, Hottenga JJ, Knol MJ, Kwok JBJ, Le Hellard S, Mather KA, Milaneschi Y, Morris DW, Nothen MM, Papiol S, Rietschel M, Santoro ML, Steen VM, Stein JL, Streit F, Tankard RM, Teumer A, van 't Ent D, van der Meer D, van Eijk KR, Vassos E, Vazquez-Bourgon J, Witt SH; IMAGEN Consortium; Adams HHH, Agartz I, Ames D, Amunts K, Andreassen OA, Arango C, Banaschewski T, Baune BT, Belangero SI, Bokde ALW, Boomsma DI, Bressan RA, Brodaty H, Buitelaar JK, Cahn W, Caspers S, Cichon S, Crespo-Facorro B, Cox SR, Dannlowski U, Elvsashagen T, Espeseth T, Falkai PG, Fisher SE, Flor H, Fullerton JM, Garavan H, Gowland PA, Grabe HJ, Hahn T, Heinz A, Hillegers M, Hoare J, Hoekstra PJ, Ikram MA, Jackowski AP, Jansen A, Jonsson EG, Kahn RS, Kircher T, Korgaonkar MS, Krug A, Lemaitre H, Malt UF, Martinot JL, McDonald C, Mitchell PB, Muetzel RL, Murray RM, Nees F, Nenadic I, Oosterlaan J, Ophoff RA, Pan PM, Penninx BWJH, Poustka L, Sachdev PS, Salum GA, Schofield PR, Schumann G, Shaw P, Sim K, Smolka MN, Stein DJ, Trollor JN, van den Berg LH, Veldink JH, Walter H, Westlye LT, Whelan R, White T, Wright MJ, Medland SE, Franke B, Thompson PM, Hulshoff Pol HE. Genetic variants associated with longitudinal changes in brain structure across the lifespan. Nat Neurosci. 2022 Apr;25(4):421-432. doi: 10.1038/s41593-022-01042-4. Epub 2022 Apr 5.

    PubMed 35383335

  • Delgado-Alvarado M, Tordesillas-Gutierrez D, Ayesa-Arriola R, Canal M, de la Foz VO, Labad J, Crespo-Facorro B. Plasma prolactin levels are associated with the severity of illness in drug-naive first-episode psychosis female patients. Arch Womens Ment Health. 2019 Jun;22(3):367-373. doi: 10.1007/s00737-018-0899-x. Epub 2018 Aug 10.

    PubMed 30097769

  • Tordesillas-Gutierrez D, Ayesa-Arriola R, Delgado-Alvarado M, Robinson JL, Lopez-Morinigo J, Pujol J, Dominguez-Ballesteros ME, David AS, Crespo-Facorro B. The right occipital lobe and poor insight in first-episode psychosis. PLoS One. 2018 Jun 1;13(6):e0197715. doi: 10.1371/journal.pone.0197715. eCollection 2018.

    PubMed 29856773

  • Ayesa-Arriola R, Setien-Suero E, Neergaard KD, Belzunces AA, Contreras F, van Haren NEM, Crespo-Facorro B. Premorbid IQ subgroups in first episode non affective psychosis patients: Long-term sex differences in function and neurocognition. Schizophr Res. 2018 Jul;197:370-377. doi: 10.1016/j.schres.2017.12.006. Epub 2017 Dec 21.

    PubMed 29275855

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aripiprazole, Quetiapine and Ziprasidone in people with Schizophrenia and Psychotic Disorders, run by Fundación Marques de Valdecilla at 1 site in Spain.

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 5 inclusion and 3 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 14 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Global cognitive index (time frame: 1 year). 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 NCT02534363, which also lists 4 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 14 Mar 2017.

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