Cocaine Abuse
Conditions
Keywords
cognitive enhancers, Nootropic Agents
Brief summary
To evaluate galantamine's effects on cognitive performance in abstinent cocaine users. Galantamine, a medication approved for treatment of Alzheimer's disease, is an acetylcholine esterase inhibitor. Galantamine also directly potentiates nicotine receptors. Both of these effects may result in improved cognitive performance in a group of subjects known to have impaired performance in various cognitive tasks.
Detailed description
Galantamine, compared to placebo, will improve cognitive performance in abstinent cocaine users. The cognitive performance will be measured with the Stroop test and 3 Cambridge Neuropsychological Test Automated Battery (CANTAB) tests: Paired Associate Learning (PAL), Delayed Pattern Recognition Memory (PRM),and Rapid Visual Information Processing (RVIP). Performance on these tests has been shown to be impaired in abstinent cocaine users, compared to healthy controls. Galantamine, compared to placebo, will not be associated with any significant changes in mood. Monitoring of mood will be achieved with 3 mood scales: 1) Center for Epidemiologic Studies Depression (CES-D) scale, Positive and Negative Affect Schedule (PANAS) and the Profile of Mood States (POMS). Currently this study is completed, Patients are no longer being enrolled. There were 28 completers. This study has been published.
Interventions
DRUGGalantamine
Galantamine 8 mg/day
DRUGplacebo
sugar pill
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Male and females, between the ages 21 and 50 * Fulfill criteria for past cocaine dependence * No cocaine use for the past 30 days * No other current dependence or abuse of other drugs or alcohol * No current medical problems and normal ECG * Not pregnant,nor breast feeding, * Using acceptable birth control methods.
Exclusion criteria
* Current major psychiatric illness including mood, psychotic or anxiety disorders * History of major medical illnesses; including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment and cardiac rhythm disturbances * Use of other medications including,drugs that slow heart rate * Known allergy to galantamine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pattern Recognition Memory (PRM) - Number Correct Answers | Baseline, Day 5 and Day 10 | Pattern Recognition Memory (PRM) tests visual pattern recognition memory in a two choice forced discrimination paradigm. 12 visual patterns are presented, then the subject must choose between each of these patterns and a novel pattern. The number of correct responses are measured. |
| Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The number of correct rejections was measured. |
| Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. A' is a measure of sensitivity to target sequences and it reflects probabilities of hits and false alarms to provide a score of sensitivity to the target regardless of response tendency. The scores range from 0 (bad) to 1 (good). |
| Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. B reflects the probability of hits and false alarms to provide a measure of the participants tendency to respond regardless of whether the target sequence is presented. The scores range from -1 to +1 with scores near +1 indicative of a subject that gave few false alarms. |
| Paired Associate Learning (PAL) - Stages Complete | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest. |
| Paired Associate Learning (PAL) - Mean Errors | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest. |
| Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Baseline, Day 5 and Day 10 | In the PRM, the subject is presented with a series of 12 visual patterns, one at a time, in the center of the screen. These patterns are designed so that they cannot easily be given verbal labels. In the recognition phase, the subject is required to choose between a pattern they have already seen and a novel pattern. The time to correct answer was measured. |
| Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. Reaction time (RT) to correct answers was measured. |
| Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Baseline, Day 5 and Day 10 | Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The total hits were measured |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Baseline, Day 5 and Day 10 | The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). The number of errors on Go trials reflected the response activation function, with fewer errors indicating greater response activation. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors. |
| Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Baseline, Day 5 and Day 10 | The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). For the Go trial, the reaction time reflected the response activation function, faster reaction time indicating greater response activation. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors. |
| Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Baseline, Day 5 and Day 10 | The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors. |
| Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Baseline, Day 5 and Day 10 | The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors. |
| Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Baseline, Day 5 and Day 10 | The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors. |
| Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Baseline, Day 5 and Day 10 | The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). For the Go/NoGo task, response inhibition was measured as the number of errors on the no- Go trials, with low errors indicating better response inhibition. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors. |
Countries
United States
Participant flow
Recruitment details
Abstinent cocaine users recruited from 2007 to 2009 using word of mouth, fliers, and newspaper advertisements. This was an outpatient study conducted in a Yale University & Veteran Affairs substance abuse research clinic.
Pre-assignment details
55 subjects were screened. 21 subjects were excluded. (Not meeting inclusion criteria n=19, declined to participate n=2). These 34 subjects were then assigned to treatment groups. Prior to the 1st day of intervention, subjects underwent an adaptation session where they were familiarized with study procedures, and baseline measures were obtained.
Participants by arm
| Arm | Count |
|---|---|
| Galantamine 8 mg/Day Galantamine 8 mg/day given for 10 days. | 17 |
| Placebo Placebo given for 10 days. | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intervention | Protocol Violation | 3 | 3 |
Baseline characteristics
| Characteristic | Galantamine 8 mg/Day | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 5.9 | 42.7 years STANDARD_DEVIATION 6.3 | 42.5 years STANDARD_DEVIATION 6.2 |
| Region of Enrollment United States | 17 participants | 17 participants | 34 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Paired Associate Learning (PAL) - Mean Errors
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Paired Associate Learning (PAL) - Mean Errors | Baseline | 31.1 errors | Standard Deviation 22.3 |
| Placebo | Paired Associate Learning (PAL) - Mean Errors | Day 5 | 23.6 errors | Standard Deviation 17.7 |
| Placebo | Paired Associate Learning (PAL) - Mean Errors | Day 10 | 17.7 errors | Standard Deviation 16.6 |
| Galantamine | Paired Associate Learning (PAL) - Mean Errors | Baseline | 25.6 errors | Standard Deviation 16.5 |
| Galantamine | Paired Associate Learning (PAL) - Mean Errors | Day 5 | 18.1 errors | Standard Deviation 11.5 |
| Galantamine | Paired Associate Learning (PAL) - Mean Errors | Day 10 | 16.8 errors | Standard Deviation 13.7 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.3Mixed Models Analysis
Primary
Paired Associate Learning (PAL) - Stages Complete
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the Paired Associate Learning (PAL) task, boxes are displayed on the screen and are opened in a random order. One or more of the boxes will contain a pattern. After the subjects have seen the patterns behind each box, the patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. An error will cause the test to open the boxes again to remind the subject of their locations. The number of boxes with patterns increases throughout the test. The stages completed and number of errors are measures of interest.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Paired Associate Learning (PAL) - Stages Complete | Baseline | 4.8 completed stages | Standard Deviation 0.4 |
| Placebo | Paired Associate Learning (PAL) - Stages Complete | Day 5 | 4.9 completed stages | Standard Deviation 0.4 |
| Placebo | Paired Associate Learning (PAL) - Stages Complete | Day 10 | 4.9 completed stages | Standard Deviation 0.4 |
| Galantamine | Paired Associate Learning (PAL) - Stages Complete | Baseline | 4.9 completed stages | Standard Deviation 0.4 |
| Galantamine | Paired Associate Learning (PAL) - Stages Complete | Day 5 | 4.9 completed stages | Standard Deviation 0.4 |
| Galantamine | Paired Associate Learning (PAL) - Stages Complete | Day 10 | 4.9 completed stages | Standard Deviation 0.4 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.7Mixed Models Analysis
Primary
Pattern Recognition Memory (PRM) - Number Correct Answers
Pattern Recognition Memory (PRM) tests visual pattern recognition memory in a two choice forced discrimination paradigm. 12 visual patterns are presented, then the subject must choose between each of these patterns and a novel pattern. The number of correct responses are measured.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pattern Recognition Memory (PRM) - Number Correct Answers | Baseline | 20.8 number correct answers | Standard Deviation 3.2 |
| Placebo | Pattern Recognition Memory (PRM) - Number Correct Answers | Day 5 | 14.9 number correct answers | Standard Deviation 2.9 |
| Placebo | Pattern Recognition Memory (PRM) - Number Correct Answers | Day 10 | 21.0 number correct answers | Standard Deviation 2.9 |
| Galantamine | Pattern Recognition Memory (PRM) - Number Correct Answers | Baseline | 20.2 number correct answers | Standard Deviation 2.5 |
| Galantamine | Pattern Recognition Memory (PRM) - Number Correct Answers | Day 5 | 20.6 number correct answers | Standard Deviation 2.5 |
| Galantamine | Pattern Recognition Memory (PRM) - Number Correct Answers | Day 10 | 20.7 number correct answers | Standard Deviation 2.2 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.3Mixed Models Analysis
Primary
Pattern Recognition Memory (PRM) - Response Time for Correct Answers
In the PRM, the subject is presented with a series of 12 visual patterns, one at a time, in the center of the screen. These patterns are designed so that they cannot easily be given verbal labels. In the recognition phase, the subject is required to choose between a pattern they have already seen and a novel pattern. The time to correct answer was measured.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Day 10 | 1995 milliseconds | Standard Deviation 479 |
| Placebo | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Baseline | 2357 milliseconds | Standard Deviation 526 |
| Placebo | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Day 5 | 2092 milliseconds | Standard Deviation 573 |
| Galantamine | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Day 5 | 2092 milliseconds | Standard Deviation 522 |
| Galantamine | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Baseline | 2439 milliseconds | Standard Deviation 685 |
| Galantamine | Pattern Recognition Memory (PRM) - Response Time for Correct Answers | Day 10 | 1889 milliseconds | Standard Deviation 364 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.3Mixed Models Analysis
Primary
Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences)
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. A' is a measure of sensitivity to target sequences and it reflects probabilities of hits and false alarms to provide a score of sensitivity to the target regardless of response tendency. The scores range from 0 (bad) to 1 (good).
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Baseline | 0.89 sensitivity index | Standard Deviation 0.04 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Day 5 | 0.90 sensitivity index | Standard Deviation 0.07 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Day 10 | 0.90 sensitivity index | Standard Deviation 0.1 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Baseline | 0.87 sensitivity index | Standard Deviation 0.07 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Day 5 | 0.90 sensitivity index | Standard Deviation 0.07 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP A' (Sensitivity to Target Sequences) | Day 10 | 0.92 sensitivity index | Standard Deviation 0.04 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.03Mixed Models Analysis
Primary
Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences)
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. B reflects the probability of hits and false alarms to provide a measure of the participants tendency to respond regardless of whether the target sequence is presented. The scores range from -1 to +1 with scores near +1 indicative of a subject that gave few false alarms.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Baseline | .88 specificity index | Standard Deviation 0.18 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Day 5 | .82 specificity index | Standard Deviation 0.22 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Day 10 | .85 specificity index | Standard Deviation 0.25 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Baseline | .88 specificity index | Standard Deviation 0.25 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Day 5 | .91 specificity index | Standard Deviation 0.11 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP B' (Strength to Detect to Target Sequences) | Day 10 | .88 specificity index | Standard Deviation 0.14 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.5Mixed Models Analysis
Primary
Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. Reaction time (RT) to correct answers was measured.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Baseline | 407.7 milliseconds | Standard Deviation 92.3 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Day 5 | 427.4 milliseconds | Standard Deviation 35.3 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Day 10 | 433.3 milliseconds | Standard Deviation 123.6 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Baseline | 476.8 milliseconds | Standard Deviation 119.3 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Day 5 | 379.2 milliseconds | Standard Deviation 71.7 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Reaction Time | Day 10 | 386.9 milliseconds | Standard Deviation 82.9 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.006Mixed Models Analysis
Primary
Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The number of correct rejections was measured.
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Baseline | 247.2 correct rejections | Standard Deviation 13.7 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Day 5 | 217.6 correct rejections | Standard Deviation 16.9 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Day 10 | 248.2 correct rejections | Standard Deviation 23.7 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Baseline | 242.4 correct rejections | Standard Deviation 15.5 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Day 5 | 247.9 correct rejections | Standard Deviation 12.9 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Correct Rejections | Day 10 | 253.9 correct rejections | Standard Deviation 12.6 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.02Mixed Models Analysis
Primary
Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits
Rapid Visual Processing test (RVIP) is a measure of sustained attention with a small working memory component that is sensitive to cholinergic enhancers. In the RVIP, subjects must detect either odd or even 3 digit sequences appearing in a box in a pseudo-random order at 100 digits per minute. The total hits were measured
Time frame: Baseline, Day 5 and Day 10
Population: There were a total of 28 completers, 14 for each treatment group. However, CANTAB data was not stored on the hard drive for one subject in the Galantamine group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Baseline | 16.7 hits | Standard Deviation 3.6 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Day 5 | 18.0 hits | Standard Deviation 5 |
| Placebo | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Day 10 | 18.0 hits | Standard Deviation 6.8 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Baseline | 14.8 hits | Standard Deviation 4.7 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Day 5 | 16.9 hits | Standard Deviation 5.4 |
| Galantamine | Performance on the Cambridge Neuropsychological Test Automated Battery (CANTAB) - RVIP Total Hits | Day 10 | 19.7 hits | Standard Deviation 4.3 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.04Mixed Models Analysis
Secondary
Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect
The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Baseline | 32.4 milliseconds | Standard Deviation 95.5 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Day 5 | 43.5 milliseconds | Standard Deviation 131.2 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Day 10 | -29.8 milliseconds | Standard Deviation 179.6 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Baseline | 13.4 milliseconds | Standard Deviation 131.9 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Day 5 | 32.1 milliseconds | Standard Deviation 96.2 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Carry-over Effect | Day 10 | 18.6 milliseconds | Standard Deviation 110.5 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.5Mixed Models Analysis
Secondary
Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time
The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Baseline | 722 milliseconds | Standard Deviation 117 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Day 5 | 734 milliseconds | Standard Deviation 126 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Day 10 | 748 milliseconds | Standard Deviation 159 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Baseline | 771 milliseconds | Standard Deviation 136 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Day 5 | 742 milliseconds | Standard Deviation 145 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Reaction Time | Day 10 | 698 milliseconds | Standard Deviation 106 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.01Mixed Models Analysis
Secondary
Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect
The Cocaine-Stroop task measures attention capture (attentional bias) secondary to cocaine cues; (Stroop effect - calculated as the difference between mean RT on cocaine words and mean RT on control words). Subjects completed 2 counterbalanced blocks (150 trials per block). One block contained 15 cocaine words and neutral words in a mixed order. The other block contained 15 control words matched in length and frequency to cocaine words, and a different set of neutral words. Subjects were required to indicate the colors in which the words were written as quickly and accurately as possible. Reaction times for identification of word color was measured. In addition, the difference in RT to words following cocaine and control words were measured (carry-over effect). Complete data for 3 participants (2 placebo and 1 galantamine) were not capture due to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Baseline | 10.5 milliseconds | Standard Deviation 66.2 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Day 5 | -19.7 milliseconds | Standard Deviation 87.6 |
| Placebo | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Day 10 | -61.5 milliseconds | Standard Deviation 183.9 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Day 10 | -33.7 milliseconds | Standard Deviation 133.2 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Baseline | -13.1 milliseconds | Standard Deviation 137.6 |
| Galantamine | Performance on the Modified Stroop Task (Cocaine-Stroop)- Stroop Effect | Day 5 | 19.6 milliseconds | Standard Deviation 149.3 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.6Mixed Models Analysis
Secondary
Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial
The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). For the Go trial, the reaction time reflected the response activation function, faster reaction time indicating greater response activation. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
Population: Participants analyzed are those that completed the treatment phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Baseline | 399.7 milliseconds | Standard Deviation 79.7 |
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Day 5 | 405.4 milliseconds | Standard Deviation 81.7 |
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Day 10 | 411.1 milliseconds | Standard Deviation 74.2 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Baseline | 375.3 milliseconds | Standard Deviation 88.5 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Day 5 | 382.6 milliseconds | Standard Deviation 79.9 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Mean Reaction Time for Correct Press on Go Trial | Day 10 | 357.8 milliseconds | Standard Deviation 109.7 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.5Mixed Models Analysis
Secondary
Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials
The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). The number of errors on Go trials reflected the response activation function, with fewer errors indicating greater response activation. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
Population: Participants analyzed are those that completed the treatment phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Baseline | 14.6 the number of errors | Standard Deviation 16.8 |
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Day 5 | 12.0 the number of errors | Standard Deviation 19.1 |
| Placebo | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Day 10 | 10.6 the number of errors | Standard Deviation 10.6 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Day 10 | 5.1 the number of errors | Standard Deviation 7.4 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Baseline | 7.2 the number of errors | Standard Deviation 7.4 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART)- Number of Errors on Go Trials | Day 5 | 3.8 the number of errors | Standard Deviation 4.1 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.8Mixed Models Analysis
Secondary
Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials
The SART is a Go / NoGo task measuring the ability to activate or inhibit responses. In this 4.5 minute task, 225 single digits (25 × 9 digits) were presented on a computer monitor. Each digit was presented for 250 ms, and was immediately followed by a mask for 900 ms. The mask consists of a ring with a diagonal cross in the center. Subjects were instructed to press a spacebar to every digit except the 3, and to give equal importance to speed and accuracy. Responses were allowed during the presentation of both the digit and mask. The digits were presented in a different random order for each subject. There were 18 practice trials, containing 2 no-response targets (3s). For the Go/NoGo task, response inhibition was measured as the number of errors on the no- Go trials, with low errors indicating better response inhibition. Complete data for 3 subjects in the Placebo group, and for 1 subject in the galantamine group were not capture do to experimenter and computer errors.
Time frame: Baseline, Day 5 and Day 10
Population: Participants analyzed are those that completed the treatment phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Baseline | 12.8 number of errors | Standard Deviation 6.4 |
| Placebo | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Day 5 | 10.7 number of errors | Standard Deviation 6.5 |
| Placebo | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Day 10 | 11.8 number of errors | Standard Deviation 7.7 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Baseline | 13.1 number of errors | Standard Deviation 5.8 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Day 5 | 10.2 number of errors | Standard Deviation 7.9 |
| Galantamine | Performance on the Sustained Attention to Response Task (SART) - Number of Errors on NoGo Trials | Day 10 | 12.2 number of errors | Standard Deviation 8.2 |
Comparison: A mixed-effect, repeated-measures model using main effect terms of treatment (placebo or galantine) and time (day of measurement). Interaction of main effects were also analyzed, with a random effect for participant. Given the hypothesis generating nature of the study, values of p\<0.05 were considered statistically significant based on two-tailed tests. Significant interactions were followed by Bonferroni post hoc pairwise comparisons.p-value: 0.9Mixed Models Analysis