Clinical trial NCT00492349: Varenicline Adjunctive Treatment in Schizophrenia
Official title: Varenicline Adjunctive Treatment in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Keywords: Varenicline
Neurobiology
clinical trial
cognitive deficits
Schizophreniform Disorder
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2007-06-27
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hamilton Depression Rating Scale (Ham-D)
timeFrame: Week 8
measure: Memory Saccadic Positional Error, Degrees
timeFrame: Week 8
measure: Predictive Pursuit Gain
timeFrame: Week 8
measure: Maintenance Pursuit Gain
timeFrame: Week 8
measure: Digit Symbol Test
timeFrame: Week 0, Week 2 and Week 8
measure: Conner's Continuous Performance Test (CPT) Detectability Score
timeFrame: Week 0, Week 2 and Week 8
measure: Antisaccade Error Rates
timeFrame: Week 0, Week 2 and Week 8
measure: P50
timeFrame: Week 0, Week 2 and Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: UMB School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical System
state: Maryland
city: Baltimore
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
Study officials:
affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine
name: L. Elliot Hong, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong LE, Thaker GK, McMahon RP, Summerfelt A, Rachbeisel J, Fuller RL, Wonodi I, Buchanan RW, Myers C, Heishman SJ, Yang J, Nye A. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 2011 Dec;68(12):1195-206. doi: 10.1001/archgenpsychiatry.2011.83. Epub 2011 Aug 1.