Schizophrenia
Conditions
Keywords
Galantamine, Schizophrenia, working memory, cognitive
Brief summary
Schizophrenia is a chronic disorder with onset of psychosis occurring in late teen early twenties, with cognitive impairments and negative symptoms frequently emerging much earlier. Such cognitive impairments and negative symptoms but much milder are also observed in high-risk groups (such as relatives of schizophrenia patients), who may or may not develop the full blown psychotic disorder. Our study plans to recruit such non-ill subjects to test the effects of galantamine on clinical/physiological/cognitive measures. This study serves several goals: If a drug is found effective in treating subtle deficits, then it will provide treatment strategy in individuals with schizophrenia spectrum personality disorders and for early intervention in schizophrenia. In addition, one of the difficulties of testing a drug on schizophrenia is that patients take other medications (i.e., antipsychotic drugs) that can change the effects of the test drug. The proposed study will be in subjects who will not be taking antipsychotic medications. Our study will be carried out in two sessions, at least one month apart. Subjects will be randomly assigned to the two possible order of administration: the drug and then placebo, or the placebo and then drug. Subjects will be given a lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing. We will administer a battery of clinical/cognitive/neurophysiological tests after the 8 mg drug dose.
Interventions
DRUGGalantamine
A lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing.
DRUGPlacebo
Subjects will be randomly assigned to the two possible order of administration: the drug and then placebo, or the placebo and then drug. Subjects will be given a lead-in 3 days of 4mg/ twice a day of galantamine (or placebo) followed by 8 mg (or placebo) on the 4th day, the day of testing.
Sponsors
National Institute of Mental Health (NIMH)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* age range of 18-64 (confirmed by drivers license or other form of identification) * the presence of 3 or more SSP symptoms (at least 2 of the SSP symptoms will be negative symptoms as defined by the schizoid traits) * the presence of visuospatial working memory impairment as defined by error in the oculomotor delayed response (ODR) task of more than 0.5 SD above the mean values in healthy control subjects * relative of an individual with schizophrenia, schizoaffective disorder, or schizophreniform disorder * able to provide written informed consent (ESC score 10 or above)
Exclusion criteria
* subjects meeting criteria for a life-time diagnosis of any one of the DSM IV, Axis I psychotic disorders (exceptions being a single past episode of major depressive disorder with psychotic features or psychotic symptoms associated with substance abuse with the substance abuse ending 6-months prior to study participation) (this is for the SSP recruitment) * subjects meeting DSM-IV criteria for current alcohol or substance dependence (other than nicotine) within the last 6 months or DSM-IV criteria for alcohol or substance abuse (other than nicotine) within the last month * medical conditions that preclude participation in drug trials or assessments of outcome measures (including significant brain, cardiac, liver, lung, endocrinological or metabolic disorders) * received any investigational drug in the preceding four weeks * pregnant or of childbearing age and not using a medically approved form of birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Brief Smell Identification Test (B-SIT) Score (Number of Correct Responses) | 5 minutes (duration usually needed to complete this test) | The Brief Smell Identification Test (B-SIT) is a 5-minute, 12-item screening test. Participants try to identify 12 different odors with four multiple choice options given for each odor. |
| Hopkins Verbal Learning Test (HVLT) Score | 15 minutes (duration needed to complete this test) | HVLT comes in 6 different forms. Forms 4 and 5 were used for this study with one form administered on the first day and the other on the second and were counterbalanced between subjects. Each form contains 12 nouns, four words each from one of three semantic categories, to be learned over the course of three learning trials. |
| Reading the Mind in the Eyes Score (Number of Correct Responses) | 10 minutes (duration needed to complete the test) | A 30 item task presents a picture of a person's eyes and the participant is asked to determine the person's mental state from 4 multiple choice options. |
| RVIP Target Hit and False Alarm (Number of Responses) | 25 minutes (duration needed to complete this test) | Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits. |
| RVIP Reaction Times (ms) | 25 minutes (total duration to test RVIP) | Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits. |
| Trust Game (Dollar Amount Earned) | 20 minutes (total duration of the trust game cognitive test) | Participants compete in a social trust game in which they are paired with a partner (the computer program). Over the course of 24 rounds he participant can offer up to $10 to their partner. The partner can either accept the offer, in which case the total amount offered is split equally between the participant and their partner (i.e. $10 is split into $5 each). Or the partner can reject the offer and receive a portion of the toal offer for themselves and give the participant nothing ($0). The total amount of money that can be offered ranges from $0-240. |
| Brief Assessment of Cognition for Schizophrenia (BACS) Score | 5 minutes (duration needed to complete the assessment) | The BACS Symbol Coding subtest will be used to assess processing speed, and the demographically corrected T score, will be used for data analysis. This test requires less than 5 minutes to administer adn provides a highly reliable measure of processing speed. There are nine symbols coded 1 through 9. Participants are given 90 seconds to match a series of these symbols with their corresponding number. The total correct matches in the participants score. Scores range from 0-110. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Facial Affect Recognition Score (Number of Responses) | 10 minutes (time usually needed to complete this test) | This computer administered test includes 40 color photogralhs of four emotions (happy, sad, angry, and fearful) balanced for the posers gender, age and ethnicity, including four low intensity and four high intensity facila expressions of each emotion, plus 8 neutral faces. The stimuli are presented in random order and subjects are asked to identify which stimuli were presented to them at the end. Performance on this test correlates with negative symptom severity |
| Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score) | 30 minutes (time needed to complete this test) | In a videotaped session, research staff engages the participant in social interaction based on a role play. The tape is rated on social skills and on Positive and Negative Affect Scale. participants are rated on a 5 point likert scale ranging from very poor (1) to very good (5) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants that were included in the study | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 53.33 years STANDARD_DEVIATION 5.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Brief Assessment of Cognition for Schizophrenia (BACS) Score
The BACS Symbol Coding subtest will be used to assess processing speed, and the demographically corrected T score, will be used for data analysis. This test requires less than 5 minutes to administer adn provides a highly reliable measure of processing speed. There are nine symbols coded 1 through 9. Participants are given 90 seconds to match a series of these symbols with their corresponding number. The total correct matches in the participants score. Scores range from 0-110.
Time frame: 5 minutes (duration needed to complete the assessment)
Population: Analyzable data for all participants was not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | Brief Assessment of Cognition for Schizophrenia (BACS) Score | 49 Number of correct responses | Standard Deviation 9.82 |
| Placebo | Brief Assessment of Cognition for Schizophrenia (BACS) Score | 52 Number of correct responses | Standard Deviation 8 |
Comparison: Comparison of the mean correct responses between galantamine and placebop-value: 0.32Wilcoxon (Mann-Whitney)
Primary
Hopkins Verbal Learning Test (HVLT) Score
HVLT comes in 6 different forms. Forms 4 and 5 were used for this study with one form administered on the first day and the other on the second and were counterbalanced between subjects. Each form contains 12 nouns, four words each from one of three semantic categories, to be learned over the course of three learning trials.
Time frame: 15 minutes (duration needed to complete this test)
Population: Analyzable data for all participants was not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 1 | 7.7 Number of correct responses | Standard Deviation 2.26 |
| Galantamine | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 2 | 9.7 Number of correct responses | Standard Deviation 1.77 |
| Galantamine | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 3 | 10.8 Number of correct responses | Standard Deviation 1.55 |
| Placebo | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 1 | 7.22 Number of correct responses | Standard Deviation 1.99 |
| Placebo | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 2 | 10.22 Number of correct responses | Standard Deviation 1.48 |
| Placebo | Hopkins Verbal Learning Test (HVLT) Score | HVLT Trial 3 | 10.78 Number of correct responses | Standard Deviation 1.3 |
Comparison: Comparison of the number of correct response on Trial 1 between galantamine and placebop-value: 0.659Wilcoxon (Mann-Whitney)
Comparison: Comparison of the number of correct response on Trial 2 between galantamine and placebop-value: 0.541Wilcoxon (Mann-Whitney)
Comparison: Comparison of the number of correct response on Trial 3 between galantamine and placebop-value: 0.838Wilcoxon (Mann-Whitney)
Primary
Reading the Mind in the Eyes Score (Number of Correct Responses)
A 30 item task presents a picture of a person's eyes and the participant is asked to determine the person's mental state from 4 multiple choice options.
Time frame: 10 minutes (duration needed to complete the test)
Population: Analyzable data was not available for all participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | Reading the Mind in the Eyes Score (Number of Correct Responses) | 24.9 Number of correct responses | Standard Deviation 5.26 |
| Placebo | Reading the Mind in the Eyes Score (Number of Correct Responses) | 24.12 Number of correct responses | Standard Deviation 3.98 |
Comparison: A comparison the mean correct responses between galantamine and placebop-value: 0.548Wilcoxon (Mann-Whitney)
Primary
RVIP Reaction Times (ms)
Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits.
Time frame: 25 minutes (total duration to test RVIP)
Population: Analyzable data for all participants was not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | RVIP Reaction Times (ms) | RVIP Practice Mean Target Reaction Time | 534.2 milliseconds | Standard Deviation 63.3 |
| Galantamine | RVIP Reaction Times (ms) | RVIP Practice Mean False Alarm Reaction Time | 290.5 milliseconds | Standard Deviation 67.5 |
| Galantamine | RVIP Reaction Times (ms) | RVIP First Half Mean Target Reaction Time | 525.1 milliseconds | Standard Deviation 58.7 |
| Galantamine | RVIP Reaction Times (ms) | RVIP First Half Mean False Alarm Reaction Time | 215 milliseconds | Standard Deviation 129 |
| Placebo | RVIP Reaction Times (ms) | RVIP First Half Mean False Alarm Reaction Time | 260 milliseconds | Standard Deviation 104 |
| Placebo | RVIP Reaction Times (ms) | RVIP Practice Mean Target Reaction Time | 581.5 milliseconds | Standard Deviation 82.1 |
| Placebo | RVIP Reaction Times (ms) | RVIP First Half Mean Target Reaction Time | 544 milliseconds | Standard Deviation 105.6 |
| Placebo | RVIP Reaction Times (ms) | RVIP Practice Mean False Alarm Reaction Time | 380.5 milliseconds | Standard Deviation 75.4 |
Comparison: Comparison of RVIP Practice Mean Target Reaction Time between Galantamine and Placebo Armsp-value: 0.161Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP Practice Mean False Alarm Reaction Time between Galantamine and Placebo Armsp-value: 0.028Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP First Half Mean Target Reaction Time between Galantamine and Placebo Armsp-value: 0.899Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP First Half Mean False Alarms Reaction Time between Galantamine and Placebo Armsp-value: 0.521Wilcoxon (Mann-Whitney)
Primary
RVIP Target Hit and False Alarm (Number of Responses)
Rapid Visual Information Processing (RVIP) measures primarily sustained attention but perhaps also working memory. The task was continuous stimuli presentation of a stream of single digits (from 1 to 9) presented in the center of the computer monitor at a rate of 1/600milliseconds; the subjects respond when the they see a target sequence of 3 odds or 3 evens in consecutive sequence. Two target sequences are separated by a minimum and maximum of 30 non-target digits.
Time frame: 25 minutes (duration needed to complete this test)
Population: Analyzable data for all participants was not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | RVIP Target Hit and False Alarm (Number of Responses) | RVIP Practice Mean False Alarms | 19.7 Number of responses | Standard Deviation 18.91 |
| Galantamine | RVIP Target Hit and False Alarm (Number of Responses) | RVIP Practice Mean Target Hits | 23.4 Number of responses | Standard Deviation 6.5 |
| Galantamine | RVIP Target Hit and False Alarm (Number of Responses) | RVIP First Half Mean Target Hits | 25.4 Number of responses | Standard Deviation 8.11 |
| Galantamine | RVIP Target Hit and False Alarm (Number of Responses) | RVIP First Half Mean False Alarms | 20.7 Number of responses | Standard Deviation 19.24 |
| Placebo | RVIP Target Hit and False Alarm (Number of Responses) | RVIP First Half Mean False Alarms | 18.88 Number of responses | Standard Deviation 26.49 |
| Placebo | RVIP Target Hit and False Alarm (Number of Responses) | RVIP First Half Mean Target Hits | 19.75 Number of responses | Standard Deviation 5.42 |
| Placebo | RVIP Target Hit and False Alarm (Number of Responses) | RVIP Practice Mean Target Hits | 22.8 Number of responses | Standard Deviation 7.47 |
| Placebo | RVIP Target Hit and False Alarm (Number of Responses) | RVIP Practice Mean False Alarms | 14.88 Number of responses | Standard Deviation 18.12 |
Comparison: Comparison of RVIP Practice Mean Target Hits between Galantamine and Placebo Armsp-value: 0.898Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP Practice Mean False Alarms between Galantamine and Placebo Armsp-value: 0.701Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP First Half Mean Target Hits between Galantamine and Placebo Armsp-value: 0.16Wilcoxon (Mann-Whitney)
Comparison: Comparison of RVIP First Half Mean False Alarms between Galantamine and Placebo Armsp-value: 0.701Wilcoxon (Mann-Whitney)
Primary
The Brief Smell Identification Test (B-SIT) Score (Number of Correct Responses)
The Brief Smell Identification Test (B-SIT) is a 5-minute, 12-item screening test. Participants try to identify 12 different odors with four multiple choice options given for each odor.
Time frame: 5 minutes (duration usually needed to complete this test)
Population: analyzable data for all participant was not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | The Brief Smell Identification Test (B-SIT) Score (Number of Correct Responses) | 10.2 Number of correct responses | Standard Deviation 1.476 |
| Placebo | The Brief Smell Identification Test (B-SIT) Score (Number of Correct Responses) | 10.222 Number of correct responses | Standard Deviation 0.833 |
p-value: 0.871Wilcoxon (Mann-Whitney)
Primary
Trust Game (Dollar Amount Earned)
Participants compete in a social trust game in which they are paired with a partner (the computer program). Over the course of 24 rounds he participant can offer up to $10 to their partner. The partner can either accept the offer, in which case the total amount offered is split equally between the participant and their partner (i.e. $10 is split into $5 each). Or the partner can reject the offer and receive a portion of the toal offer for themselves and give the participant nothing ($0). The total amount of money that can be offered ranges from $0-240.
Time frame: 20 minutes (total duration of the trust game cognitive test)
Population: Analyzable data for all participants was not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Galantamine | Trust Game (Dollar Amount Earned) | 147.7 Dollars | Standard Deviation 81.1 |
| Placebo | Trust Game (Dollar Amount Earned) | 131.4 Dollars | Standard Deviation 42.3 |
Comparison: Comparison of the mean total amount offered during the trust game between the galantamine and placebo groupsp-value: 0.67Wilcoxon (Mann-Whitney)
Secondary
Facial Affect Recognition Score (Number of Responses)
This computer administered test includes 40 color photogralhs of four emotions (happy, sad, angry, and fearful) balanced for the posers gender, age and ethnicity, including four low intensity and four high intensity facila expressions of each emotion, plus 8 neutral faces. The stimuli are presented in random order and subjects are asked to identify which stimuli were presented to them at the end. Performance on this test correlates with negative symptom severity
Time frame: 10 minutes (time usually needed to complete this test)
Population: analyzable data was not available for all participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | Facial Affect Recognition Score (Number of Responses) | Facial Affect Total | 31.2 Number of Responses | Standard Deviation 4.49 |
| Galantamine | Facial Affect Recognition Score (Number of Responses) | Facial Affect Hits | 12.3 Number of Responses | Standard Deviation 7.07 |
| Galantamine | Facial Affect Recognition Score (Number of Responses) | Facial Affect False Alarms | 5.1 Number of Responses | Standard Deviation 4.46 |
| Placebo | Facial Affect Recognition Score (Number of Responses) | Facial Affect Total | 33 Number of Responses | Standard Deviation 5.21 |
| Placebo | Facial Affect Recognition Score (Number of Responses) | Facial Affect Hits | 14.38 Number of Responses | Standard Deviation 4.75 |
| Placebo | Facial Affect Recognition Score (Number of Responses) | Facial Affect False Alarms | 5.38 Number of Responses | Standard Deviation 3.07 |
Comparison: Comparison of Facial Affect Total Responses between galantamine and placebop-value: 0.797Wilcoxon (Mann-Whitney)
Comparison: Comparison of Facial Affect Total Hits between galantamine and placebop-value: 0.669Wilcoxon (Mann-Whitney)
Comparison: Comparison of Facial Affect Total False Alarms between galantamine and placebop-value: 0.668Wilcoxon (Mann-Whitney)
Secondary
Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score)
In a videotaped session, research staff engages the participant in social interaction based on a role play. The tape is rated on social skills and on Positive and Negative Affect Scale. participants are rated on a 5 point likert scale ranging from very poor (1) to very good (5)
Time frame: 30 minutes (time needed to complete this test)
Population: analyzable data was not available for all participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Galantamine | Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score) | Overall Affect | 3.958 units on a scale | Standard Deviation 0.68 |
| Galantamine | Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score) | Overall Social Skill | 4.15 units on a scale | Standard Deviation 0.58 |
| Placebo | Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score) | Overall Affect | 3.8 units on a scale | Standard Deviation 0.632 |
| Placebo | Social Affiliation Measured by Social Affiliative Role Play (Rating Scale Score) | Overall Social Skill | 3.8 units on a scale | Standard Deviation 0.715 |
Comparison: Comparison of Overall Affect between galantamine and placebop-value: 0.626Wilcoxon (Mann-Whitney)
Comparison: Comparison of Overall Social Skill between galantamine and placebop-value: 0.234Wilcoxon (Mann-Whitney)