Adjunctive Vortioxetine in Schizophrenia (AVIS)

Northwell Health

Status and phase: Active, not recruiting; Phase 4

Conditions: Schizophrenia; Negative Symptoms

Treatments: Other: Placebo; Drug: Vortioxetine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02357797

14-645

Details and patient eligibility

About

This is a 16-week, randomized, double-blind, parallel group, placebo-controlled study comparing adjunctive vortioxetine with identically appearing adjunctive placebo pills in 88 stable patients with a research diagnosis of schizophrenia determined with the Structured Clinical Interview for DSM (SCID). Patient randomization will be stratified by illness duration (i.e., </=5 years and >5 years) in order to allow for post-hoc analyses examining whether earlier illness moderates greater negative and /or cognitive symptom reduction in response to vortioxetine.

Full description

This is a 16-week, randomized, double-blind, parallel group, placebo-controlled study comparing adjunctive vortioxetine with identically appearing adjunctive placebo pills in 88 stable patients with a research diagnosis of schizophrenia determined with the Structured Clinical Interview for DSM (SCID). Patient randomization will be stratified by illness duration (i.e., </=5 years and >5 years) in order to allow for post-hoc analyses examining whether earlier illness moderates greater negative and /or cognitive symptom reduction in response to vortioxetine.

Patients with clinical stability for at least 3 months and stable antipsychotic and psychotropic medication treatment for at least the last 4 weeks and without relevant depression, positive psychotic symptoms or extrapyramidal symptoms EPS will be eligible. After written informed consent, patients will undergo a screening visit to confirm full study eligibility. If all in- and exclusion criteria are fulfilled, patients will undergo a baseline assessment and then be randomized 1:1 to 16 weeks of adjunctive treatment with vortioxetine or placebo. Subsequently, patients will be seen at week 1, 2, 4 and monthly for the next 3 months.

Enrollment: 88 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Outpatient
2. SCID diagnosis of schizophrenia
3. Age 18-65 years old
4. Treated with an adequate dose of one or a maximum of two antipsychotic medications for at least 3 months, with a stable dose for at least the last 4 weeks, and willing to continue for up to 16 weeks.
5. No antidepressant treatment for at least 8 weeks prior to randomization.
6. Treatment with other concomitant, non-antipsychotic, psychiatric medications is allowed, but must be unchanged for at least 8 weeks, with a stable dose for at least the last 4 weeks, and willing to continue for 16 weeks. Benzodiazepines must not be given within 8 hours of the cognitive assessment. Treatment with non-psychiatric medications is unrestricted.
7. PANSS Negative subscore >14 with at least two of the items at a level >/=4 (moderate)
8. PANSS Positive subscore </=14 with not more than one of the items at a level >/=4 (moderate) for patients who have been stable outpatients for <1 year. A PANSS Positive subscore of </=18 is acceptable for patients who have been stable outpatients for >/=1year and whose psychotic symptoms do not affect behavior in a clinically relevant way as per investigator assessment. - . In order to avoid simple double counting, any rating on P1 ("delusions") will not be considered as an additional symptom for determination of eligibility based on PANSS positive subscore when a specific delusion is present that is rated either on P5 ("grandiosity") or P6 ("suspiciousness/paranoia"), whereas delusions not captured by P5 ("grandiosity") or P6 ("suspiciousness/paranoia"), will be rated under P1 ("delusions") and counted toward the sum score used to determine study eligibility).
9. HAMD-17 total score </=12
10. Simpson Angus Score of any item <3
11. English-speaking
12. Competent and willing to sign informed consent

Exclusion criteria

1. Structural brain disease
2. Mental retardation by history and estimated IQ <70 (WRAT-III Word Reading)
3. Autism-spectrum disorder diagnosis by history
4. Any serious chronic medical illnesses that in the view of the investigator will interfere with the patient's ability to comply with the study procedures or that will interfere with cognition.
5. Active substance abuse or dependence in the past 8 weeks
6. Intolerance to or inefficacy of vortioxetine in the past
7. Acute anger to self or others as per investigator assessment
8. Pregnant or breastfeeding females
9. Unwilling or unable to be sexually abstinent or not using an effective form of birth control if they are sexually active
10. Current treatment with a Monoamine Oxidase Inhibitor (MAOI)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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88 participants in 2 patient groups, including a placebo group

Vortioxetine

Active Comparator group

Description:

Vortioxetine will be initiated at 10 mg / day for 1 month, followed by 20 mg /day for the remainder of the trial. The dose of vortioxetine can be lowered to 10 mg for tolerability reasons.

Treatment:

Drug: Vortioxetine

Placebo

Placebo Comparator group

Description:

Matching placebo pills will be initiated at 10 mg / day for 1 month, followed by 20 mg /day for the remainder of the trial. The dose of placebo can be lowered to 10 mg for tolerability reasons.

Treatment:

Other: Placebo