Varenicline Adjunctive Treatment in Schizophrenia

NCT ID: NCT00492349

Last Updated: 2022-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-04-30

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Varenicline

Group Type: EXPERIMENTAL

Varenicline

Intervention Type: DRUG

Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks

Interventions

Varenicline

Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks

Intervention Type: DRUG

Placebo

Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks

Intervention Type: DRUG

Other Intervention Names

Chantix

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

L. Elliot Hong

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

L. Elliot Hong, M.D.

Role: PRINCIPAL_INVESTIGATOR

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine

Locations

UMB School of Medicine

Baltimore, Maryland, United States

University of Maryland Medical System

Baltimore, Maryland, United States

Maryland Psychiatric Research Center

Baltimore, Maryland, United States

Countries

United States

References

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type: DERIVED

PMID: 37142273 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21810630 (View on PubMed)

Other Identifiers

HP-00040322

Identifier Type: -

Identifier Source: org_study_id