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| Name | Class |
|---|---|
| Stanley Medical Research Institute | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Varenicline |
|
| 2 | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | Varenicline 0.5mg po qd x 7 days then titrated to Varenicline 0.5mg po bid x 7 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| L. Elliot Hong, M.D. | Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UMB School of Medicine | Baltimore | Maryland | 21201 | United States | ||
| University of Maryland Medical System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37142273 | Derived | 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. | |
| 21810630 | Derived | 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. |
| Label | URL |
|---|---|
| Click here for more information about the study: Varenicline Adjunctive Treatment in Schizophrenia | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Varenicline | Varenicline Treatment Group |
| FG001 | Placebo | Placebo Control Group |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Varenicline | |
| BG001 | Placebo | |
| BG002 | Total |
| 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 | 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. | Posted | Mean | Standard Error | units on a scale | Week 8 |
|
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| 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 |
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The small number of nonsmokers in the placebo arm could have led to reduced power and false negatives.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| L. Elliot Hong, M.D. | University of Maryland | 410-402-6828 | ehong@mprc.umaryland.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D000068580 | Varenicline |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo 0.5mg po qd x 7 days then titrated to Placebo 0.5mg po bid x 7 weeks |
|
| 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. | 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. | 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. | Week 0, Week 2 and Week 8 |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| Maryland Psychiatric Research Center | Baltimore | Maryland | 21228 | United States |
Total of all reporting groups
| years |
|
| Sex: Female, Male | Baseline data were available for participants who completed 2 weeks in the study | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BPRS Total | BRIEF PSYCHIATRIC RATING SCALE has 20 items: 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe. Score range from 20 to 140. | Mean | Standard Deviation | units on a scale |
|
| Ham-D Total Score | HAMILTON DEPRESSION RATING SCALE In general, the higher the total score the more severe the depression. One can use the following to classify severity: 0 - 13 mild; 14-17 mild to moderate; >17 moderate to severe. However, in this trial, these categorical classifications of severity were not used. Only the raw score was used to compare between the treatment arm and the placebo arm. | Mean | Standard Deviation | units on a scale |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | 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. | Posted | Mean | Standard Error | degrees | Week 8 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Error | velocity ratio | Week 8 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Error | velocity ratio | Week 8 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | Week 0, Week 2 and Week 8 |
|
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | Week 0, Week 2 and Week 8 |
|
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | percentage errors | Week 0, Week 2 and Week 8 |
|
|
|
|
| Primary | 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. | Posted | Mean | Standard Error | microvolts | Week 0, Week 2 and Week 8 |
|
|
|
| 0 |
| 35 |
| 0 |
| 35 |
| EG001 | Placebo | Placebo | 0 | 34 | 0 | 34 |
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| D011810 | Quinoxalines |
| Week 8 |
|
| Week 8 |
|
| Week 8 |
|
| Week 8 |
|