SchizophreniaPhase 2NCT01093365
Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
A Phase 2 study testing Varenicline in people with Schizophrenia and Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Smokers with schizophrenia have more difficulties quitting smoking than smokers without a mental disorder. Varenicline (Champix) is a new stop smoking medication with a unique mechanism of action. It is a nicotine-like drug which is not addictive and not associated with the health risks of tobacco smoking. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2010to Aug 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- For all subjects
- Age 18-55
- Estimated IQ ≥80 using the Shipley scale
- Capable of giving informed consent
- Not taking any form of nicotine replacement therapy
- Additional inclusion criteria for smokers:
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- Non-treatment seeking cigarette smokers:
- A score of 5 or higher on the Fagerstrom Test for Nicotine Dependence (FTND)
- Self reported smoking of at least 10 cigarettes per day as measured by the Weekly Smoking Inventory (NOTE: Cigarette smoking is verified by a Smokerlyzer® test, with a cut off of 10 ppm and plasma cotinine levels ≥150 ng/ml)
- Cigarette smokers with Schizophrenia:
- Diagnosis of schizophrenia/schizoaffective disorder (confirmed by the SCID for DSM-IV)
- Stable remission from positive symptoms of psychosis as judged by a score of <70 on the The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and a psychiatric evaluation
- Receiving a stable dose of antipsychotic medication(s)for the past month
- Additional inclusion criteria for healthy smokers and non-smokers:
- No diagnosis for any Axis I psychiatric disorder (Except past history of major depression)
Who cannot join
- For all subjects
- Substance abuse other than cigarette smoking.
- History of alcohol/drug abuse in the 3 months before study enrollment
- Hypersensitivity to varenicline (Champix)
- Use of opioids (meperidine, oxycodone, methadone, etc).
- A history of renal insufficiency
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- Gastrointestinal problems including irritable bowel syndrome
- Exposure to chemotherapy
- A history of dementia and other neurological illness like epilepsy or medical condition known to significantly influence neurocognitive function
- Inability to learn the neuropsychological tasks during the training session
- Failure to demonstrate a deficit of at least 0.5 standard deviations below average levels of non-psychiatric control performance the on the Visuospatial Working Memory (VSWM) task
- Pregnancy
- Nursing women
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre for Addiction and Mental Health (33 Russell street)
Toronto, Ontario, M5S 2S1
About this study
Smokers with schizophrenia have more difficulties quitting smoking than smokers without a mental disorder. Varenicline (Champix) is a new stop smoking medication with a unique mechanism of action. It is a nicotine-like drug which is not addictive and not associated with the health risks of tobacco smoking.
Varenicline (VAR) binds to sites in the brain called nicotine receptors that play an important role in nicotine dependence. People with schizophrenia have difficulties in concentrating and remembering. Scientists believe that people with schizophrenia use smoking to remedy their cognitive problems. We will test VAR to see if it improves cognitive problems in smokers with schizophrenia in comparison to non-mentally ill smokers to determine whether people with schizophrenia get direct benefit from this nicotine-like drug. It is hypothesized that VAR (in comparison to a placebo) will reduce aspects of cognitive impairment in smokers and nonsmokers with schizophrenia.
Read the detailed description
Schizophrenia is characterized by deficits in neurocognitive function, including executive function, attention, and spatial and verbal memory. Central nicotinic acetylcholine receptors (nAChR) are dysregulated in schizophrenia. It has been shown that neurocognitive deficits in schizophrenia improve by administration of nicotine, nicotinic agonists or cigarette smoking. Hence, it is believed that cigarette smoking may remedy cognitive deficits in schizophrenia and in fact some persons with schizophrenia may be "self-medicating" with tobacco to counter such cognitive problems.
The prevalence rates of cigarette smoking in persons with schizophrenia are higher than in the general population (58-88% vs. 25% respectively). This population also has a nicotine dependence rate of around 80 % and a high relapse rate after smoking cessation. Additionally the leading cause of medical problems and death in people with schizophrenia is tobacco addiction. Research that addresses the problem of smoking in schizophrenia is of great importance.
Varenicline (VAR), an α4β2 nAChR partial agonist, approved for smoking cessation, mimics the effect of nicotine by stimulating nAChRs, and releasing sufficient dopamine in order to reduce craving and withdrawal effects.
This study will follow four groups of subjects (N=40) that will receive neuropsychological and psychiatric testing in three consecutive sessions (smoking satiation, abstinence and reinstatement) separated by at least one week over 3 weeks. The groups are:
- cigarette smokers with schizophrenia (N=10),
- non-smokers with schizophrenia (N=10),
- healthy cigarette smoking controls (N=10),
- non-smoking controls (N=10).
All groups will be age- and sex- matched. Pre-treatment with varenicline (VAR) or placebo will start on Day 1 of each test session will be as follows: 1) 0.0 mg/day 2) 0.5 mg twice daily 3) or 1 mg twice daily for 3 days. Testing days will be separated by at least 1 week apart to rule out medication carry-over effects.
If nicotinic acetylcholine receptors can be stimulated resulting in more dopamine release and improved neurocognitive function without inducing deleterious health effects it may be of benefit to persons with schizophrenia who smoke tobacco.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Varenicline
- Keywords
- Schizophrenia, Schizoaffective Disorder, Varenicline, Champix, Chantix, Nicotine, Nicotinic receptor, Dopamine, Acetylcholine, Cigarette, Smoking, Tobacco, Executive function, Working memory, Verbal memory, Cognitive function, Neuropsychological function
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called Chantix, Champix
- 0.0 mg orally twice per day for three days (placebo)
- 0.5 mg orally twice per day for three days
- 1.0 mg orally twice per day for three days
| Study group | Role | What they receive |
|---|---|---|
| Schizophrenia | Experimental | To measure the effects of varenicline on cognition of smokers with schizophrenia. Receives: Drug: Varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Computerized testing of neuropsychological functioning
- Trail Making Test, Part A
- Trail Making Test, Part B
- Visuospatial Working Memory (VSWM) and Digit Span of WAIS
- Hopkins Verbal Learning Test - Revised (HVLT-V)
- Continuous Performance Task (CPT)
Measured: Three times per week for three consecutive weeks
Tiffany Urge to Smoke Scale
Measured: Three times per week for three consecutive weeks
Minnesota Withdrawal Scale
Measured: Three times over a two day period for three consecutive weeks
Secondary outcomes (2)
Pre-pulse inhibition
Measurement of startle reactivity to tones by EMG and the inhibition of the EMG response by exposure to a "pre-pulse".
Measured: 3 times per week for 3 weeks
Smoking topography
Topographic assessment of smoking behavior (e.g., number of puffs per cigarette, puff volume, amount of time between puffs)
Measured: 3 times a week for 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Tony George, Centre for Addiction and Mental Health
- Investigators
- Tony P George, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01093365
- Sponsor's protocol ID
- 067/2009
- Status last verified
- Aug 2016
- First submitted
- 24 Mar 2010
- Last updated
- 26 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Johnstone S, Sorkhou M, Rabin RA, George TP. Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia. Drug Alcohol Depend. 2022 May 1;234:109412. doi: 10.1016/j.drugalcdep.2022.109412. Epub 2022 Mar 28.
PubMed 35395548
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
- ClinicalTrials.gov ID
- NCT01093365
- Acronym / sponsor ID
- 067/2009
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- Schizophrenia, Schizoaffective Disorder, Varenicline, Champix, Chantix, Nicotine, Nicotinic receptor, Dopamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Mar 2010
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 25 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Smokers with schizophrenia have more difficulties quitting smoking than smokers without a mental disorder. Varenicline (Champix) is a new stop smoking medication with a unique mechanism of action. It is a nicotine-like drug which is not addictive and not associated with the health risks of tobacco smoking.
Varenicline (VAR) binds to sites in the brain called nicotine receptors that play an important role in nicotine dependence. People with schizophrenia have difficulties in concentrating and remembering. Scientists believe that people with schizophrenia use smoking to remedy their cognitive problems. We will test VAR to see if it improves cognitive problems in smokers with schizophrenia in comparison to non-mentally ill smokers to determine whether people with schizophrenia get direct benefit from this nicotine-like drug. It is hypothesized that VAR (in comparison to a placebo) will reduce aspects of cognitive impairment in smokers and nonsmokers with schizophrenia.
Detailed description
Schizophrenia is characterized by deficits in neurocognitive function, including executive function, attention, and spatial and verbal memory. Central nicotinic acetylcholine receptors (nAChR) are dysregulated in schizophrenia. It has been shown that neurocognitive deficits in schizophrenia improve by administration of nicotine, nicotinic agonists or cigarette smoking. Hence, it is believed that cigarette smoking may remedy cognitive deficits in schizophrenia and in fact some persons with schizophrenia may be "self-medicating" with tobacco to counter such cognitive problems.
The prevalence rates of cigarette smoking in persons with schizophrenia are higher than in the general population (58-88% vs. 25% respectively). This population also has a nicotine dependence rate of around 80 % and a high relapse rate after smoking cessation. Additionally the leading cause of medical problems and death in people with schizophrenia is tobacco addiction. Research that addresses the problem of smoking in schizophrenia is of great importance.
Varenicline (VAR), an α4β2 nAChR partial agonist, approved for smoking cessation, mimics the effect of nicotine by stimulating nAChRs, and releasing sufficient dopamine in order to reduce craving and withdrawal effects.
This study will follow four groups of subjects (N=40) that will receive neuropsychological and psychiatric testing in three consecutive sessions (smoking satiation, abstinence and reinstatement) separated by at least one week over 3 weeks. The groups are:
- cigarette smokers with schizophrenia (N=10),
- non-smokers with schizophrenia (N=10),
- healthy cigarette smoking controls (N=10),
- non-smoking controls (N=10).
All groups will be age- and sex- matched. Pre-treatment with varenicline (VAR) or placebo will start on Day 1 of each test session will be as follows: 1) 0.0 mg/day 2) 0.5 mg twice daily 3) or 1 mg twice daily for 3 days. Testing days will be separated by at least 1 week apart to rule out medication carry-over effects.
If nicotinic acetylcholine receptors can be stimulated resulting in more dopamine release and improved neurocognitive function without inducing deleterious health effects it may be of benefit to persons with schizophrenia who smoke tobacco.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Schizophrenia | Experimental | Drug: VareniclineTo measure the effects of varenicline on cognition of smokers with schizophrenia. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- For all subjects
- Age 18-55
- Estimated IQ ≥80 using the Shipley scale
- Capable of giving informed consent
- Not taking any form of nicotine replacement therapy
Key exclusion criteria (13 listed)
- For all subjects
- Substance abuse other than cigarette smoking.
- History of alcohol/drug abuse in the 3 months before study enrollment
- Hypersensitivity to varenicline (Champix)
- Use of opioids (meperidine, oxycodone, methadone, etc).
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: Chantix, Champix* 0.0 mg orally twice per day for three days (placebo) * 0.5 mg orally twice per day for three days * 1.0 mg orally twice per day for three days | Drug | Schizophrenia |
Primary outcome
Computerized testing of neuropsychological functioning
Time frame: Three times per week for three consecutive weeks
* Trail Making Test, Part A * Trail Making Test, Part B * Visuospatial Working Memory (VSWM) and Digit Span of WAIS * Hopkins Verbal Learning Test - Revised (HVLT-V) * Continuous Performance Task (CPT)
Tiffany Urge to Smoke Scale
Time frame: Three times per week for three consecutive weeks
Minnesota Withdrawal Scale
Time frame: Three times over a two day period for three consecutive weeks
2 secondary outcomes
Pre-pulse inhibition
Time frame: 3 times per week for 3 weeks
Smoking topography
Time frame: 3 times a week for 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2016.
- Derived from this study: PubMed 35395548Johnstone S, Sorkhou M, Rabin RA, George TP. Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia. Drug Alcohol Depend. 2022 May 1;234:109412. doi: 10.1016/j.drugalcdep.2022.109412. Epub 2022 Mar 28.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating CentreLink provided by the sponsor.
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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.
Tony P George, MD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varenicline in people with Schizophrenia and Schizoaffective Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 15 inclusion and 13 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 26 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Computerized testing of neuropsychological functioning (time frame: Three times per week for three consecutive weeks). The study lists 3 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 NCT01093365, which also lists 1 linked publication.
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 26 Aug 2016.