Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| FDA IND 102,411 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Varenicline | Experimental | Varenciline 1-2 mg/day |
|
| Matched Placebo | Placebo Comparator | placebo for varenicline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | Varenicline 1-2 mg/day |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Cotinine Level | plasma cotinine | 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. | basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Diagnosis of Schizophrenia or Schizoaffective Disorder Current Cigarette Smoker or History of Chronic Cigarette smoking Age 18-65 Currently taking antipsychotic medication
Exclusion Criteria:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert C. Smith, MD, PhD | Nathan Kline Institute for Psychiatric Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Manhattan Psychatirc Center | New York | New York | 10035 | United States | ||
| Nathan Kline Insitute for Psychiatric Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26730716 | Background | 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. | |
| 37142273 |
Not provided
Not provided
Overall, 93 subjects were consented, 2 withdrew consent before randomization, and 87 provided evaluable data on at least one outcome measure. The number enrolled 93, is less than the number started 91, because 2 patients withdrew consent before randomization
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Varenicline | Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day |
| FG001 | Matched Placebo | placebo for varenicline Placebo for varenicline: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Varenicline | Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day |
| BG001 | Matched Placebo | placebo for varenicline Placebo for varenicline: Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cotinine Level | plasma cotinine | Data were available for cotinine analysis in mixed model analysis of co covariance on 34 participants in the varenicline arms and 36 participants in the placebo arm. | Posted | Mean | Standard Error | cotinine ng/ml | Baseline, 4 weeks, 8 weeks |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Varenicline | Varenicline 1-2 mg/day Varenicline: Varenicline 1-2 mg/day |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| psychiatric decompensation not study drug related | Psychiatric disorders | Non-systematic Assessment | after discharge from hospital patient decoenssated because of drug abuse and noncompliance with medication |
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert C. Smith MD | Nathan Kline Institute for Psychiatric Research | 845-398-6531 | rsmith@nki.rfmh.org |
Not provided
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D000073865 | Cigarette Smoking |
| D012907 | Smoking |
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D000073869 | Tobacco Smoking |
| D001519 | Behavior |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068580 | Varenicline |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo for varenicline | Drug | Placebo |
|
| 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. | baseline, 4 weeks, 8 weeks |
| Orangeburg |
| New York |
| 10962 |
| United States |
| Peking University Institute of Mental Health | Beijing | 100191 | China |
| The Division of Psychiatry, Chaim Sheba Medical Center | Tel Litwinsky | 52621 | Israel |
| 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | 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. | N's varied from 25-32 in varenicline group and 29-35 in placebo group because all subjects did not complete all parts of MATRICS battery.Maximum number of participants is entered for number of participants because this cell entry does not allow entry of variable number of participations ( e.g. 25-32). for different scores.. | Posted | Mean | Standard Error | T scores from MATRICS battery | basline and 8 weeks (or end of study iif patient ended participation before the 8-weeks) |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Error | units on a scale | baseline, 4 weeks, 8 weeks |
|
|
|
| Secondary | 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. | Not all patients had relevant responses on Calgary Depression Scale. Data are analyzed for 36 subjects randomized to varenicline and 38 subjects randomized to placebo (total N=74). | Posted | Mean | Standard Error | Scores on a scale | baseline, 4 weeks, 8 weeks |
|
|
|
| 2 |
| 45 |
| 0 |
| 45 |
| EG001 | Matched Placebo | placebo for varenicline Placebo for varenicline: Placebo | 1 | 46 | 0 | 46 |
|
| auditory hallucination not study drug related | Psychiatric disorders | Systematic Assessment | patient developed auditory hallucinations although symptom scores had decreased on varenicline |
|
| verbal agression | Psychiatric disorders | Non-systematic Assessment | verbal aggression lead to [psychiatric hospitalization. Patient on placebo study drug](streamdown:incomplete-link) |
|
Not provided
Not provided
| D064424 | Tobacco Use |
| D019965 | Neurocognitive Disorders |
| D011810 | Quinoxalines |
| MATRICS Speed of Processing diff from baseline |
|
|
| MATRICS attention-vigilance diff from baseline |
|
|
| MATRICS working memory diff from baseline |
|
|
| MATRICS verbal learning diff from baseline |
|
|
| MATRICS visual learning diff from baseline |
|
|
| MATRICS reasoning-rob sol diff from baseline |
|
|
| PANSS Depression Factor wk4-basline diff |
|
| PANSS depressor factor wk8-baseline diff |
|