CAVES: Cognitive Effects of Adjuvant Vortioxetine in Early Schizophrenia

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04895488

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clinical trial to assess the efficacy of Vortioxetine compared with treatment as usual in early schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Cognitive Impairment With Primary Psychotic Disorder Negative Symptoms With Primary Psychotic Disorder	Drug: Vortioxetine Drug: Usual Antipsychotic Treatment	Phase 2/Phase 3

Detailed Description

Clinical trial to assess the efficacy of Vortioxetine, compared with treatment as usual in early schizophrenia. Propose: To investigate the effect of Vortioxetine in cognitive functioning and negative symptoms severity in early schizophrenia.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

A two arm, Open-label, randomized, Cross-over Design and single-center clinical trial Phase II b /Phase III.A two arm, Open-label, randomized, Cross-over Design and single-center clinical trial Phase II b /Phase III.

Masking:

None (Open Label)

Masking Description:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cognitive Effects of Adjuvant Vortioxetine in Early Schizophrenia

Anticipated Study Start Date :

Nov 15, 2021

Anticipated Primary Completion Date :

Nov 15, 2025

Anticipated Study Completion Date :

Dec 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Vortioxetine+Usual antipsychotic treatment (TAU) Drug: First treatment phase: Vortioxetine 10 mg 1 tablet/d for 2 weeks added to Usual antipsychotic treatment, followed by Vortioxetine 20mg 1tablet/d for 22 weeks added to Usual antipsychotic treatment. Wash-out period 2 weeks	Drug: Vortioxetine First treatment phase: vortioxetine will be initiated at 10 mg / day for 2 weeks, followed by 20 mg /day for 22 weeks. The dose of vortioxetine can be lowered to 5 mg or 10 mg for tolerability reasons at clinician criteria. Wash-out period 2 weeks Drug: Usual Antipsychotic Treatment Second treatment phase. Usual antipsychotic treatment for 26 weeks: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician. Other Names: TAU
Active Comparator: Arm B: Usual antipsychotic treatment (TAU) Second treatment phase: Usual antipsychotic treatment: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician.	Drug: Vortioxetine First treatment phase: vortioxetine will be initiated at 10 mg / day for 2 weeks, followed by 20 mg /day for 22 weeks. The dose of vortioxetine can be lowered to 5 mg or 10 mg for tolerability reasons at clinician criteria. Wash-out period 2 weeks Drug: Usual Antipsychotic Treatment Second treatment phase. Usual antipsychotic treatment for 26 weeks: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician. Other Names: TAU

Arm

Intervention/Treatment

Experimental: Arm A: Vortioxetine+Usual antipsychotic treatment (TAU)

Drug: First treatment phase: Vortioxetine 10 mg 1 tablet/d for 2 weeks added to Usual antipsychotic treatment, followed by Vortioxetine 20mg 1tablet/d for 22 weeks added to Usual antipsychotic treatment. Wash-out period 2 weeks

Drug: Vortioxetine

First treatment phase: vortioxetine will be initiated at 10 mg / day for 2 weeks, followed by 20 mg /day for 22 weeks. The dose of vortioxetine can be lowered to 5 mg or 10 mg for tolerability reasons at clinician criteria. Wash-out period 2 weeks

Drug: Usual Antipsychotic Treatment

Second treatment phase. Usual antipsychotic treatment for 26 weeks: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician.

Other Names:

TAU

Active Comparator: Arm B: Usual antipsychotic treatment (TAU)

Second treatment phase: Usual antipsychotic treatment: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician.

Drug: Vortioxetine

Drug: Usual Antipsychotic Treatment

Second treatment phase. Usual antipsychotic treatment for 26 weeks: Allows for whatever medication, routine support, or referral to other services was felt appropriate by the clinician.

Other Names:

TAU

Outcome Measures

Primary Outcome Measures

To assess the effectiveness of Vortioxetine vs. TAU measured by the change in Brief Assessment of Cognition in Schizophrenia (BACS App) scores [Baseline, week 24, week 26 and week 50]
To assess the effectiveness of Vortioxetine vs. TAU in the treatment of cognitive impairments in early psychosis, measured by the change From Baseline to Week 24 in BACS App scores using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores

Secondary Outcome Measures

To assess the effectiveness of Vortioxetine vs. TAU measured by the change in Negative Symptoms severity (Scale for Assessment of Negative Symptoms (SANS) and Negative Symptom Assessment-4 (NSA-4) total scores) [Baseline, week 4, week 12, week 24, week 26, week 30, week 38 and week 50]
To assess the effectiveness of Vortioxetine vs. TAU in the treatment of negative symptoms in early psychosis, measured by the change in Negative Symptoms severity (SANS, NSA-4 total scores) from baseline to end of trial.

Other Outcome Measures

To assess the effectiveness of Vortioxetine vs. TAU measured by the change in general functioning [baseline, week 12, week 24, week 26, week 38 and week 50]
To assess the effectiveness of Vortioxetine vs. TAU in the treatment of cognitive impairments in early psychosis, measured by the change in general functioning (Global Assessment of Functioning (GAF) total score)
To assess the safety of Vortioxetine measured through the communication of any serious adverse event. [from informed consent form (ICF) signature to 52 weeks]
To assess the safety of Vortioxetine in patients with early psychosis measured through the communication of any serious adverse event evaluated for relationship with the Investigational Medicinal Product (IMP).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Outpatient
Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM - SCID) diagnosis of Schizophrenia spectrum disorders.
Age >18-50 years old
Stable antipsychotic medication doses during at least 4 weeks ( all second generation antipsychotics excluding clozapine).
No antidepressant treatment for at least 8 weeks prior to randomization.
PANSS Negative subscore >14 with at least two of the items at a level >/=4 (moderate)
PANSS Positive subscore </=14 with not more than one of the items at a level >/=4 (moderate)
Hamilton Depression Rating Scale (HAMD-17) total score </=12
Simpson Angus Score of any item <2
Behaviorally Anchored Rating Scale (BARS) of any item </= 1
Competent and willing to sign informed consent
The patient, if a woman, must: agree not to try to become pregnant during the study and use adequate, highly effective contraception

Exclusion Criteria:

Patients taking any antidepressant and its use cannot be discontinued at least 8 weeks prior to randomization.
Structural brain disease (based on previous medical records)
Cognitive disability by history and estimated intelligence quotient (IQ) <70 (ID DSM-5 diagnosis).
Any serious chronic medical illnesses that may interfere with the patient's ability to comply with the study procedures or that will interfere with cognition.
Organic mental disorders, or mental disorders due to a general medical condition. Any neurological or neurodegenerative disorders.
Any current diagnosis of substance abuse or dependence.
Serious risk of suicide.
Patients with thyroid conditions.
Intolerance to or inefficacy of vortioxetine in the past. Patients who had failed treatment with vortioxetine were also excluded.
Pregnant or breastfeeding female.