SchizophreniaPhase 4NCT00802919
Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors
A Phase 4 study testing Varenicline in people with Schizophrenia and Cigarette Smoking, run by Nathan Kline Institute for Psychiatric Research at 4 sites in 3 countries.
Trial summary
This is a 8-week double-blind placebo controlled parallel group study of the efficacy of varenicline (Chantix) for smoking cessation in schizophrenic patients, and its effect on cognitive function in patients with schizophrenia.At some sits evaluation of smoking measures is extended to 12 weeks. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Cigarette Smoking
- What is being tested?
- Varenicline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Sep 2008to Dec 2013
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Schizophrenia or Schizoaffective Disorder Current Cigarette Smoker or History of Chronic Cigarette smoking Age 18-65 Currently taking antipsychotic medication
Who cannot join
- prior history of hospitalization for acute myocardial infarction or stroke, or persistent angina pectoris with current symptoms Patients who have previously tried varenicline and have stopped taking it because of side-effects of severe nausea or vomiting suicide attempt in the last year and or have had prominent or serious suicidal thoughts in the past year Women who are pregnant, nursing, or unable to use reliable contraception significant renal impairment(Creatinine ≥ 1.5) baseline Hamilton Depression Scores is >20
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
Manhattan Psychatirc Center
New York, New York, 10035
Nathan Kline Insitute for Psychiatric Research
Orangeburg, New York, 10962
Israel1 site
The Division of Psychiatry, Chaim Sheba Medical Center
Tel HaShomer, 52621
About this study
Official title: Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors, Independent Investigator Study
This is a 8-week double-blind placebo controlled parallel group study of the efficacy of varenicline (Chantix) for smoking cessation in schizophrenic patients, and its effect on cognitive function in patients with schizophrenia.At some sits evaluation of smoking measures is extended to 12 weeks. Correlations will be made with biological predictors of efficacy: a) measures of nicotinic receptors in lymphocytes b) DNMT1 and GAD67 mRNA in lymphocytes. Subjects will be current cigarette smokers or history of regular smokers.
Read the detailed description
This was a double-blind placebo controlled study of varenicline and matched placebo in patients with a diagnosis of schizophrenia or schizoaffective psychosis who were treated with antipsychotic medication and were cigarette smokers. Three sites (2 U.S., 1 Israel) were supported by the Stanley grant. A similar independently supported study was conducted in Beijing, China. We were allowed to access these data and combine them for our analysis of results. Subjects at each site participated in a protocol which was approved by their institutional IRB. All subjects signed informed consent.
The study evaluated multiple measures of cigarette smoking, cognitive functions by MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia), and psychiatric symptoms by PANSS (Positive and Negative Symptom Scale), SANS (Schedule For Assessment Of Negative Symptoms), and Calgary Depression scales. Lymphocytes were collected for measurement of epigenetically related mRNA's.
- Conditions
- Schizophrenia, Cigarette Smoking
- Being tested
- Varenicline, Placebo for varenicline
- Keywords
- schizophrenia, smoking, nicotine, cognitive deficits, nicotinic receptors, Cognitive Deficits in Schizophrenia
- Medical subject headings
- Schizophrenia, Cigarette Smoking, Smoking, 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 1-2 mg/day
Placebo for vareniclineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Varenicline | Experimental | Varenciline 1-2 mg/day Receives: Drug: Varenicline |
| Matched Placebo | Placebo comparator | placebo for varenicline Receives: Drug: Placebo for varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cotinine Level
plasma cotinine
Measured: Baseline, 4 weeks, 8 weeks
Change From Baseline in Cognitive Performance
The MATRICS Consensus Cognitive Battery (MCCB)(Measurement and Treatment Research to Improve Cognition in Schizophrenia) was used to measure cognitive performance. Six Domain scores and a Composite score are calculated by the proprietary MCCB Computer Scoring Program (modified beta version) from raw scores on 10 individually administered subtests. The social cognition test was not assessed in this study. The Domain T-scores are percentile-ranked and range from <20 (<0.1 percentile) to >80 (>99.9 percentile). The Composite scores are also percentile-ranked and range from <213 (T<20, <0.1 percentile) to >487 (T>80, >99.9 percentile). Higher scores after baseline represent better outcomes. Here we report difference scores from post-treatment and baseline with positive difference scores representing better outcomes.
Measured: basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks)
Secondary outcomes (2)
Change From Baseline in Psychiatric Symptoms
The Positive and Negative Syndrome Scale (PANSS) was used to measure psychiatric symptoms. Item scores ranged from 1 (Absent) to 6 (Severe) for symptoms on the Positive Scale (total subscale range: 7-42), the Negative Scale (total subscale range: 7-42), and the General Psychopathology Scale (total subscale range:16-96). All three subscales were summed for the PANSS total score (total scale range: 30-180). Scores closer to 30 after baseline represented better outcomes. Here we report difference scores from post-treatment and baseline with negative difference scores representing better outcomes.
Measured: baseline, 4 weeks, 8 weeks
Change From Basellne in Calgary Depression Scale Score
The Calgary Depression Scale for Schizophrenia. The scale has 9 items with ratings of 0 to 3 on each item. Total score can vary from 0 to 27. Higher scores indicate more depression. Negative change scores indicate decreasing depression.
Measured: baseline, 4 weeks, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2013
- Study completionDec 2013
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.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research
- Investigators
- Robert C. Smith, MD, PhD, Principal investigator, Nathan Kline Institute for Psychiatric Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00802919
- Sponsor's protocol ID
- 081/C02
- Other IDs
- FDA IND 102,411
- Status last verified
- Oct 2017
- First submitted
- 4 Dec 2008
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Smith RC, Amiaz R, Si TM, Maayan L, Jin H, Boules S, Sershen H, Li C, Ren J, Liu Y, Youseff M, Lajtha A, Guidotti A, Weiser M, Davis JM. Varenicline Effects on Smoking, Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial. PLoS One. 2016 Jan 5;11(1):e0143490. doi: 10.1371/journal.pone.0143490. eCollection 2016.
PubMed 26730716Livingstone-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
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Varenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors, Independent Investigator Study
- ClinicalTrials.gov ID
- NCT00802919
- Acronym / sponsor ID
- 081/C02
- Conditions
- Schizophrenia, Cigarette Smoking
- Keywords
- schizophrenia, smoking, nicotine, cognitive deficits, nicotinic receptors, Cognitive Deficits in Schizophrenia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 5 Dec 2008 (estimated)
- Results
- Posted 2 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 8-week double-blind placebo controlled parallel group study of the efficacy of varenicline (Chantix) for smoking cessation in schizophrenic patients, and its effect on cognitive function in patients with schizophrenia.At some sits evaluation of smoking measures is extended to 12 weeks. Correlations will be made with biological predictors of efficacy: a) measures of nicotinic receptors in lymphocytes b) DNMT1 and GAD67 mRNA in lymphocytes. Subjects will be current cigarette smokers or history of regular smokers.
Detailed description
This was a double-blind placebo controlled study of varenicline and matched placebo in patients with a diagnosis of schizophrenia or schizoaffective psychosis who were treated with antipsychotic medication and were cigarette smokers. Three sites (2 U.S., 1 Israel) were supported by the Stanley grant. A similar independently supported study was conducted in Beijing, China. We were allowed to access these data and combine them for our analysis of results. Subjects at each site participated in a protocol which was approved by their institutional IRB. All subjects signed informed consent.
The study evaluated multiple measures of cigarette smoking, cognitive functions by MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia), and psychiatric symptoms by PANSS (Positive and Negative Symptom Scale), SANS (Schedule For Assessment Of Negative Symptoms), and Calgary Depression scales. Lymphocytes were collected for measurement of epigenetically related mRNA's.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline | Experimental | Drug: VareniclineVarenciline 1-2 mg/day |
| Matched Placebo | Placebo comparator | Drug: Placebo for vareniclineplacebo for varenicline |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosis of Schizophrenia or Schizoaffective Disorder Current Cigarette Smoker or History of Chronic Cigarette smoking Age 18-65 Currently taking antipsychotic medication
Key exclusion criteria (1 listed)
- prior history of hospitalization for acute myocardial infarction or stroke, or persistent angina pectoris with current symptoms Patients who have previously tried varenicline and have stopped taking it because of side-effects of severe nausea or vomiting suicide attempt in the last year and or have had prominent or serious suicidal thoughts in the past year Women who are pregnant, nursing, or unable to use reliable contraception significant renal impairment(Creatinine ≥ 1.5) baseline Hamilton Depression Scores is >20
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 1-2 mg/day | Drug | Varenicline |
| Placebo for vareniclinePlacebo | Drug | Matched Placebo |
Primary outcome
Cotinine Level
Time frame: Baseline, 4 weeks, 8 weeks
plasma cotinine
Change From Baseline in Cognitive Performance
Time frame: basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks)
The MATRICS Consensus Cognitive Battery (MCCB)(Measurement and Treatment Research to Improve Cognition in Schizophrenia) was used to measure cognitive performance. Six Domain scores and a Composite score are calculated by the proprietary MCCB Computer Scoring Program (modified beta version) from raw scores on 10 individually administered subtests. The social cognition test was not assessed in this study. The Domain T-scores are percentile-ranked and range from <20 (<0.1 percentile) to >80 (>99.9 percentile). The Composite scores are also percentile-ranked and range from <213 (T<20, <0.1 percentile) to >487 (T>80, >99.9 percentile). Higher scores after baseline represent better outcomes. Here we report difference scores from post-treatment and baseline with positive difference scores representing better outcomes.
2 secondary outcomes
Change From Baseline in Psychiatric Symptoms
Time frame: baseline, 4 weeks, 8 weeks
Change From Basellne in Calgary Depression Scale Score
Time frame: baseline, 4 weeks, 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26730716Smith RC, Amiaz R, Si TM, Maayan L, Jin H, Boules S, Sershen H, Li C, Ren J, Liu Y, Youseff M, Lajtha A, Guidotti A, Weiser M, Davis JM. Varenicline Effects on Smoking, Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial. PLoS One. 2016 Jan 5;11(1):e0143490. doi: 10.1371/journal.pone.0143490. eCollection 2016.
- 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.
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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.
Robert C. Smith, MD, PhD principal investigator
Nathan Kline Institute for Psychiatric Research
4 sites in 3 countries: 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 Cigarette Smoking, run by Nathan Kline Institute for Psychiatric Research at 4 sites in 3 countries.
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 1 inclusion and 1 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 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, China, Israel. 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 2 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?
Cotinine Level (time frame: Baseline, 4 weeks, 8 weeks). The study lists 2 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 NCT00802919, 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 2 Dec 2017.