Varenicline Adjunctive Treatment in Schizophrenia

University of Maryland Baltimore (UMB)

Status and phase

Completed

Phase 4

Conditions

Schizophreniform Disorder

Schizophrenia

Schizoaffective Disorder

Treatments

Drug: Placebo

Drug: Varenicline

Study type

Interventional

Funder types

Other

Identifiers

NCT00492349

HP-00040322

Details and patient eligibility

About

The principal aim of the project is to conduct an off-label adjunctive clinical trial evaluating varenicline as a treatment for core neurobiological and clinical deficits in schizophrenia, in addition to evaluating for smoking cessation in schizophrenia patients.

Full description

This is a double-blind, placebo controlled clinical trial in schizophrenia patients. Outcome measures include biomarkers and clinical symptoms and functions, and smoking cessation. Neurobiological and cognitive markers will be measured for short term (2 weeks) and longer-term (8 weeks). Current schizophrenia treatments are mostly ineffective against primary negative symptoms and the cognitive and information processing deficits associated with the disorder. Previous research has identified several neurophysiological deficits in schizophrenia that are enduring, frequently occurring before psychosis, and mark the disease liability. These schizophrenia endophenotypes provide important targets for novel treatment development as they represent the core deficits of the disorder. We hypothesize that sustained nicotinic and dopaminergic modulation by varenicline may ameliorate the core neurobiological deficits seen in schizophrenia patients, which would lead to subsequent clinical improvement. Neurobiological and neurocognitive markers and clinical and functional measures will be obtained to determine 1) short-term effect of varenicline on biomarkers; and 2) longer-term improvement in clinical symptoms, smoking cessation, and functions; and how biomarker changes predict these improvements.

Enrollment

91 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18-60
DSM-IV Diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder
Clinically stable with no change in antipsychotic medications and increase of daily dose for 4 weeks prior to enrollment
Sufficient understanding of the study and risks (ESC score 10 or above)

Exclusion criteria

Major medical illness history including, but not limited to, history of heart attack, stroke, TIA (transient ischemic attack)
History of organic brain disorders that may affect neurophysiological measurements, including seizure disorder, brain tumor, head injury with evidence of significant cognitive deterioration
DSM-IV diagnosis of substance dependence within 6 months except nicotine and marijuana
On nicotine replacement therapy (nicotine patch, gum, or nasal spray)
Uncontrolled blood pressure (persistent systolic above 155 or diastolic above 95)
EKG of second or third degree atrioventricular (AV) block
Renal insufficiency with estimated creatinine clearance <40 ml/min
Women who have positive urine pregnancy tests
Women who are pregnant, plan to become pregnant, or in breastfeeding