SchizophreniaPhase 4NCT00492349

Varenicline Adjunctive Treatment in Schizophrenia

A Phase 4 study testing Varenicline in people with Schizophrenia and Schizoaffective Disorder, run by University of Maryland, Baltimore at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
What is being tested?: Varenicline
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 91 participants
Where: 3 sitesUnited States
Study dates: May 2007to Apr 2011
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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)

Who cannot join

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

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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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

UMB School of Medicine
Baltimore, Maryland, 21201
University of Maryland Medical System
Baltimore, Maryland, 21201
Maryland Psychiatric Research Center
Baltimore, Maryland, 21228

Other trials in United States

About this study

Read the 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
Being tested: Varenicline, Placebo
Keywords: Varenicline, Neurobiology, clinical trial, cognitive deficits, Schizophreniform Disorder
Medical subject headings: Schizophrenia, Psychotic Disorders, Cognition Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VareniclineDrug
Also called Chantix
Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks
PlaceboDrug
Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks

Study groups in NCT00492349
Study group	Role	What they receive
1	Experimental	Varenicline Receives: Drug: Varenicline
2	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Hamilton Depression Rating Scale (Ham-D)
Ham-D Total Score (range 0 to 54, higher score is worse). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 8
Memory Saccadic Positional Error, Degrees
A saccade is a quick eye movement. Spatial working memory was assessed by memory saccade. Participants were asked to focus on a target while a peripheral cue was flashed. Participants were signaled to look in the direction of the peripheral cue when the central target was removed, and the positional error was calculated as the distance between the saccadic and peripheral target positions. Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 8
Predictive Pursuit Gain
Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Participants are asked to track a target with their eyes. Participants may use a predictive mechanism to perform the tracking. The pursuit gain using the predictive mechanism is calculated. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 8
Maintenance Pursuit Gain
Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Eye velocity during the regular eye-tracking period (without foveal stabilization) divided by target velocity was used to calculate the maintenance pursuit gain. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 8
Digit Symbol Test
Digit symbol test score (0 to no definite upper range, higher score is better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 0, Week 2 and Week 8
Conner's Continuous Performance Test (CPT) Detectability Score
Conner's CPT Detectability Score (no set normal range, higher is generally better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 0, Week 2 and Week 8
Antisaccade Error Rates
In antisaccade, participants were asked to focus on a central target. When a peripheral cue was presented, participants were asked to look in an equidistant and opposite direction of the peripheral cue. The error rate is calculated as the number of trials in which the participant looked toward the cue, rather than in the opposite direction, divided by the total number of trials. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 0, Week 2 and Week 8
P50
P50 response is a measure of the amplitude of the brain wave in response to a sound, where the positive going amplitude of the brain wave occurring at about 50 milliseconds after the sound. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Measured: Week 0, Week 2 and Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Apr 2011

First posted27 Jun 2007 (estimated)
Study startMay 2007
Primary completionMay 2010
Study completionApr 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 91 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00492349
Sponsor's protocol ID: HP-00040322
Status last verified: Dec 2017
First submitted: 26 Jun 2007
Last updated: 5 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 37142273
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.
PubMed 21810630

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Varenicline Adjunctive Treatment in Schizophrenia
ClinicalTrials.gov ID: NCT00492349
Acronym / sponsor ID: HP-00040322
Conditions: Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
Keywords: Varenicline, Neurobiology, clinical trial, cognitive deficits, Schizophreniform Disorder
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 91 participants (actual)
Lead sponsor: University of Maryland, BaltimoreUniversity, hospital or other
Collaborators: Stanley Medical Research Institute
Study start: May 2007
Primary completion: May 2010 (actual)
Study completion: Apr 2011 (actual)
First posted: 27 Jun 2007 (estimated)
Results: Posted 11 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: VareniclineVarenicline
2	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (9 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VareniclineAlso: ChantixVarenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks	Drug	1
PlaceboPlacebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks	Drug	2

Primary outcome

Hamilton Depression Rating Scale (Ham-D)
Time frame: Week 8
Ham-D Total Score (range 0 to 54, higher score is worse). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Memory Saccadic Positional Error, Degrees
Time frame: Week 8
A saccade is a quick eye movement. Spatial working memory was assessed by memory saccade. Participants were asked to focus on a target while a peripheral cue was flashed. Participants were signaled to look in the direction of the peripheral cue when the central target was removed, and the positional error was calculated as the distance between the saccadic and peripheral target positions. Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Predictive Pursuit Gain
Time frame: Week 8
Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Participants are asked to track a target with their eyes. Participants may use a predictive mechanism to perform the tracking. The pursuit gain using the predictive mechanism is calculated. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Maintenance Pursuit Gain
Time frame: Week 8
Pursuit gain is the averaged artifact-free eye velocity divided by target velocity. Eye velocity during the regular eye-tracking period (without foveal stabilization) divided by target velocity was used to calculate the maintenance pursuit gain. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Digit Symbol Test
Time frame: Week 0, Week 2 and Week 8
Digit symbol test score (0 to no definite upper range, higher score is better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Conner's Continuous Performance Test (CPT) Detectability Score
Time frame: Week 0, Week 2 and Week 8
Conner's CPT Detectability Score (no set normal range, higher is generally better). Definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
Antisaccade Error Rates
Time frame: Week 0, Week 2 and Week 8
In antisaccade, participants were asked to focus on a central target. When a peripheral cue was presented, participants were asked to look in an equidistant and opposite direction of the peripheral cue. The error rate is calculated as the number of trials in which the participant looked toward the cue, rather than in the opposite direction, divided by the total number of trials. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.
P50
Time frame: Week 0, Week 2 and Week 8
P50 response is a measure of the amplitude of the brain wave in response to a sound, where the positive going amplitude of the brain wave occurring at about 50 milliseconds after the sound. Further definition is fully described in a peer-review journal reported at Arch Gen Psychiatry 2011 Dec;68(12):1195-206.

Results and safety

Results posted to the registry on 11 Dec 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Varenicline	35	32
Placebo	34	27

Primary outcome: Hamilton Depression Rating Scale (Ham-D)

Time frame: Week 8. Mean (Standard Error). Unit: units on a scale

Measure	Varenicline n = 32	Placebo n = 27
Smoker	22.9 (3.2)	20.6 (3.4)
Nonsmoker	19.4 (3.2)	18.6 (2.2)

Primary outcome: Memory Saccadic Positional Error, Degrees

Time frame: Week 8. Mean (Standard Error). Unit: degrees

Measure	Varenicline n = 32	Placebo n = 27
Smoker	1.6 (0.2)	1.7 (0.2)
Nonsmoker	1.7 (0.1)	1.8 (0.2)

Primary outcome: Predictive Pursuit Gain

Time frame: Week 8. Mean (Standard Error). Unit: velocity ratio

Measure	Varenicline n = 32	Placebo n = 27
Smoker	0.31 (0.03)	0.34 (0.04)
Nonsmoker	0.24 (0.04)	0.31 (0.04)

Primary outcome: Maintenance Pursuit Gain

Time frame: Week 8. Mean (Standard Error). Unit: velocity ratio

Measure	Varenicline n = 32	Placebo n = 27
Smoker	0.8 (0.1)	0.8 (0.04)
Nonsmoker	0.8 (0.1)	0.8 (0.1)

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Varenicline	0 of 35 (0%)	0 of 35 (0%)	Not reported
Placebo	0 of 34 (0%)	0 of 34 (0%)	Not reported

Limitations and caveats (from the sponsor): The small number of nonsmokers in the placebo arm could have led to reduced power and false negatives.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37142273Livingstone-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.
Derived from this study: PubMed 21810630Hong 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.
Click here for more information about the study: Varenicline Adjunctive Treatment in SchizophreniaLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

L. Elliot Hong, M.D. principal investigator

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

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Varenicline in people with Schizophrenia and Schizoaffective Disorder, run by University of Maryland, Baltimore at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hamilton Depression Rating Scale (Ham-D) (time frame: Week 8). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00492349, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.