Cognitive Effects of Adjuvant Vortioxetine in Early Schizophrenia (CAVES)

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

Study Overview

• Status: Recruiting
• Conditions: Negative Symptoms With Primary Psychotic Disorder; Cognitive Impairment With Primary Psychotic Disorder
• Intervention / Treatment: Drug: Vortioxetine; Drug: Usual Antipsychotic Treatment

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 Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Clara M. Rosso Fernández, PhD; Phone Number: +34 955 013414; Email: claram.rosso.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocío
    • Contact: Benedicto Crespo Facorro, Professor; Phone Number: +34671596675; Email: benedicto.crespo.sspa@juntadeandalucia.es
    • Principal Investigator: Benedicto Crespo Facorro, Professor
    • Sub-Investigator: Miguel Ruiz Veguilla, PhD
    • Contact: Idalino Rocha, MSc; Phone Number: +34689366067; Email: idalino.rocha@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Patients taking any antidepressant and its use cannot be discontinued at least 8 weeks prior to randomization.
2. Structural brain disease (based on previous medical records)
3. Cognitive disability by history and estimated intelligence quotient (IQ) <70 (ID DSM-5 diagnosis).
4. 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.
5. Organic mental disorders, or mental disorders due to a general medical condition. Any neurological or neurodegenerative disorders.
6. Any current diagnosis of substance abuse or dependence.
7. Serious risk of suicide.
8. Patients with thyroid conditions.
9. Intolerance to or inefficacy of vortioxetine in the past. Patients who had failed treatment with vortioxetine were also excluded.
10. Pregnant or breastfeeding female.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effectiveness of Vortioxetine vs. TAU measured by the change in Brief Assessment of Cognition in Schizophrenia (BACS App) scores	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	Baseline, week 24, week 26 and week 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline, week 4, week 12, week 24, week 26, week 30, week 38 and week 50

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effectiveness of Vortioxetine vs. TAU measured by the change in general functioning	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)	baseline, week 12, week 24, week 26, week 38 and week 50
To assess the safety of Vortioxetine measured through the communication of any serious adverse event.	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).	from informed consent form (ICF) signature to 52 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: Benedicto Crespo Facorro, Professor, benedicto.crespo.sspa@juntadeandalucia.es

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Estimated): December 20, 2024
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Selective Serotonin Reuptake Inhibitors; Vortioxetine; Antipsychotic Agents
• Other Study ID Numbers: CAVES; 2021-001333-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No