Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
schizophrenia, cognition, cognitive remediation, nicotine
Brief summary
Schizophrenia is marked by problems in attention, memory and problem solving. These deficits predict long-term functional outcome such as the ability to live independently and maintain employment, but they are not ameliorated by currently available medications. Cognitive training improves these functions to some degree, but this approach is time- and resource-intensive. The current project aims at enhancing and accelerating the benefits that people with schizophrenia derive from cognitive training by administering nicotine during some of the training sessions. This would provide the proof of principle for a type of treatment intervention to improve cognitive symptoms of schizophrenia. The current project aims at determining whether the intermittent presence of nicotine during cognitive training exercises in people with schizophrenia will shorten the training period necessary to induce significant and clinically relevant improvement and enhance the improvement seen after a training period of specified length. Hypothesis 1a: Nicotine administration during training will increase the size of all measured effects of the training intervention, and will accelerate the time course of performance enhancement on the MCCB and training exercise progression parameters. Hypothesis 1b: The larger training effects in the Nicotine Group will persist beyond the end of the intervention. Hypothesis 2a: Within-session progress on the training exercises will be larger in the presence of nicotine than in the presence of placebo. Hypothesis 2b: These acute nicotine-induced performance elevations will persist beyond the presence of nicotine through subsequent non-drug training sessions, giving evidence of an acute facilitation of learning processes.
Interventions
BEHAVIORALCognitive remediation training
DRUGNicotine polacrilex lozenge
Of interest are the effects of nicotine on cognitive remediation training benefits.
Sponsors
National Institute of Mental Health (NIMH)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-60 years. * DSM diagnosis of schizophrenia or schizoaffective disorder. * Ability to give written informed consent. * Either currently smoking and not attempting to quit, or having smoked no more than 80 cigarettes, cigarillos or cigars in lifetime and not at all within the last year. * Normal or corrected to normal vision (at least 20/50). * Four weeks of stable pharmacological treatment (same psychiatric medication at same dose) and no foreseeable changes at enrollment.
Exclusion criteria
* Alcohol or substance abuse or dependence other than nicotine within the last 12 months. * Uncontrolled hypertension (resting systolic blood pressure above 150 or diastolic above 90 mm Hg). * History of myocardial infarction, heart failure, angina, stroke or severe arrhythmias. * ECG abnormalities. * History of neurological conditions such as stroke, seizures, dementia or organic brain syndrome. * Mental retardation. * Pregnant, verified by urine pregnancy test for females. * Breast-feeding. * Treated with benztropine currently or within the last four weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MATRICS Consensus Cognitive Battery (MCCB) Composite Score | baseline (week 0), weeks 4 and 7 of intervention, end-of-intervention (week 10), 4-week follow-up | The MCCB is an FDA-approved assessment tool for trials of cognition-enhancing treatments in people with schizophrenia. The MCCB is comprised of the following domains: 1) Speed of Processing; 2) Attention/Vigilance; 3) Working Memory; 4) Verbal Learning; 5) Visual Learning; 6) Reasoning and Problem Solving; and 7) Social Cognition. The composite score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Better performance is reflected by higher scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Assessment Interview (CAI) Score | baseline (week 0) and post-intervention (week 10) | Clinician-administered interview about daily life cognitive functioning. The CAI assesses 10 items related to working memory, attention/vigilance, learning/memory, problem solving, processing speed, and social cognition. The total score ranges from 1 (inability to maintain personal hygiene due to cognitive deficits) to 100 (superior cognitive functioning in a wide range of activities). A score of 55 corresponds to moderate cognitive symptoms, e.g. persistent problems paying attention or forgetting scheduled events. |
| Change in Abbreviated Schizophrenia Quality of Life Scale Score | baseline (week 0) and post-intervention (week 10) | Semi-structured clinician interview measuring functional outcome and quality of life in people with schizophrenia. Includes subjective questions regarding life satisfaction and objective indicators of social and occupational role functioning during preceding 4 weeks. Seven items are scored on a 0 (severe impairment) to 6 (high functioning) scale. The total score ranges from 0 to 42, with larger values reflecting higher functioning. |
| UCSD Performance-Based Skills Assessment (UPSA) Score | baseline (week 0) and post-intervention (week 10) | Measures ability to perform real-life tasks by standardized role-play. Scores reflect percent correct, i.e. range from 0-100 with higher scores representing better performance. |
| Calgary Depression Scale Score | baseline (week 0), post-intervention (week 10) | Clinician scale developed to assess the level of depression in schizophrenia. 9 items assess symptoms of depression and overall rater impression on a scale from 0 (absent) to 3 (severe). |
| Scale for the Assessment of Negative Symptoms (SANS) Score | baseline (week 0), post-intervention (week 10) | Clinician rating scale of negative symptoms in schizophrenia. Within each of 5 domains, separate symptoms are rated from 0 (absent) to 5 (severe). Total scores are the sum of 22 subscales and range from 0 to 110, with larger values reflecting higher negative symptoms. |
| Brief Psychiatric Rating Scale (BPRS) Score | baseline (week 0), post-intervention (week 10) | Clinician rating scale to measure psychotic symptoms. Each of 20 items is scored 1-7. Total scores are the sum of all items and range from 20 to 140, with larger values reflecting worse symptoms. |
| Training Exercise Parameters: Visual and Sound Sweeps | baseline (week 0), post-intervention (week 10), 4-week follow-up | Some of the Posit Science exercises provide an assessment tool of training progress on task parameters, which adjust continuously to keep performance at \ 85% correct. Enhanced sensory processing speed and precision is considered the central building block of training benefits. Therefore, we analyzed the two exercises aimed at training these processes. Performance is quantified as stimulus presentation time in ms of visual or sound sweeps, which the participant has to judge in terms of change across space or time. Smaller values reflect better performance. Visual and sound sweeps were averaged. |
| Change in Working Memory Capacity | baseline (week 1) and post-intervention (week 10) | Derived from a computerized change localization task. One to four colored squares are shown for 100 ms. After a delay, they reappear and the task is to click on the one square that has changed color (50% chance). Performance is expressed as the percentage of correct responses. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Remediation Training With Nicotine Participants complete daily sessions of Posit Science cognitive remediation training for 10 weeks. Twice a week, participants consume a 2 mg (for non-smokers) or 4 mg (for smokers) nicotine polacrilex lozenge prior to the training.
Cognitive remediation training
Nicotine polacrilex lozenge: Of interest are the effects of nicotine on cognitive remediation training benefits. | 14 |
| Cognitive Remediation Training Without Nicotine Participants complete daily Posit Science cognitive remediation training for 10 weeks. Twice a week, participants consume a placebo lozenge prior to the training.
Cognitive remediation training | 17 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Cognitive Remediation Training With Nicotine | Cognitive Remediation Training Without Nicotine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 17 Participants | 31 Participants |
| Age, Continuous | 43.0 years STANDARD_DEVIATION 11 | 43.8 years STANDARD_DEVIATION 12 | 43.5 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 17 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 16 Participants |
| Region of Enrollment United States | 14 participants | 17 participants | 31 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
| Smoking status Non-smoker | 8 Participants | 10 Participants | 18 Participants |
| Smoking status Smokers | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 17 |
| other Total, other adverse events | 0 / 14 | 0 / 17 |
| serious Total, serious adverse events | 0 / 14 | 0 / 17 |
Outcome results
Primary
MATRICS Consensus Cognitive Battery (MCCB) Composite Score
The MCCB is an FDA-approved assessment tool for trials of cognition-enhancing treatments in people with schizophrenia. The MCCB is comprised of the following domains: 1) Speed of Processing; 2) Attention/Vigilance; 3) Working Memory; 4) Verbal Learning; 5) Visual Learning; 6) Reasoning and Problem Solving; and 7) Social Cognition. The composite score is standardized to a T-scale (mean=50, standard deviation=10) based on healthy control normative data. Better performance is reflected by higher scores.
Time frame: baseline (week 0), weeks 4 and 7 of intervention, end-of-intervention (week 10), 4-week follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 4 | 32.50 score on a scale | Standard Deviation 14.98 |
| Cognitive Remediation Training With Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 10 (end of intervention) | 34.60 score on a scale | Standard Deviation 14.38 |
| Cognitive Remediation Training With Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 7 | 35.30 score on a scale | Standard Deviation 13.7 |
| Cognitive Remediation Training With Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 4-week follow-up | 35.00 score on a scale | Standard Deviation 12.67 |
| Cognitive Remediation Training With Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Baseline | 32.30 score on a scale | Standard Deviation 15.42 |
| Cognitive Remediation Training Without Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 4-week follow-up | 37.87 score on a scale | Standard Deviation 10.14 |
| Cognitive Remediation Training Without Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Baseline | 33.87 score on a scale | Standard Deviation 10.4 |
| Cognitive Remediation Training Without Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 4 | 35.47 score on a scale | Standard Deviation 9.02 |
| Cognitive Remediation Training Without Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 7 | 36.87 score on a scale | Standard Deviation 9.75 |
| Cognitive Remediation Training Without Nicotine | MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Week 10 (end of intervention) | 36.67 score on a scale | Standard Deviation 10.27 |
Secondary
Brief Psychiatric Rating Scale (BPRS) Score
Clinician rating scale to measure psychotic symptoms. Each of 20 items is scored 1-7. Total scores are the sum of all items and range from 20 to 140, with larger values reflecting worse symptoms.
Time frame: baseline (week 0), post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Brief Psychiatric Rating Scale (BPRS) Score | Baseline | 39.40 score on a scale | Standard Deviation 9.14 |
| Cognitive Remediation Training With Nicotine | Brief Psychiatric Rating Scale (BPRS) Score | Post-intervention (10 weeks) | 39.50 score on a scale | Standard Deviation 9.43 |
| Cognitive Remediation Training Without Nicotine | Brief Psychiatric Rating Scale (BPRS) Score | Baseline | 37.33 score on a scale | Standard Deviation 7.87 |
| Cognitive Remediation Training Without Nicotine | Brief Psychiatric Rating Scale (BPRS) Score | Post-intervention (10 weeks) | 36.53 score on a scale | Standard Deviation 5.55 |
Secondary
Calgary Depression Scale Score
Clinician scale developed to assess the level of depression in schizophrenia. 9 items assess symptoms of depression and overall rater impression on a scale from 0 (absent) to 3 (severe).
Time frame: baseline (week 0), post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Calgary Depression Scale Score | Baseline | 2.40 score on a scale | Standard Deviation 2.45 |
| Cognitive Remediation Training With Nicotine | Calgary Depression Scale Score | Post-intervention (10 weeks) | 2.50 score on a scale | Standard Deviation 2.59 |
| Cognitive Remediation Training Without Nicotine | Calgary Depression Scale Score | Baseline | 2.07 score on a scale | Standard Deviation 2.28 |
| Cognitive Remediation Training Without Nicotine | Calgary Depression Scale Score | Post-intervention (10 weeks) | 1.40 score on a scale | Standard Deviation 1.59 |
Secondary
Change in Abbreviated Schizophrenia Quality of Life Scale Score
Semi-structured clinician interview measuring functional outcome and quality of life in people with schizophrenia. Includes subjective questions regarding life satisfaction and objective indicators of social and occupational role functioning during preceding 4 weeks. Seven items are scored on a 0 (severe impairment) to 6 (high functioning) scale. The total score ranges from 0 to 42, with larger values reflecting higher functioning.
Time frame: baseline (week 0) and post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Change in Abbreviated Schizophrenia Quality of Life Scale Score | Baseline | 22.30 score on a scale | Standard Deviation 5.7 |
| Cognitive Remediation Training With Nicotine | Change in Abbreviated Schizophrenia Quality of Life Scale Score | Post-intervention (week 10) | 24.90 score on a scale | Standard Deviation 5.88 |
| Cognitive Remediation Training Without Nicotine | Change in Abbreviated Schizophrenia Quality of Life Scale Score | Baseline | 20.29 score on a scale | Standard Deviation 5.99 |
| Cognitive Remediation Training Without Nicotine | Change in Abbreviated Schizophrenia Quality of Life Scale Score | Post-intervention (week 10) | 23.00 score on a scale | Standard Deviation 4.02 |
Secondary
Change in Working Memory Capacity
Derived from a computerized change localization task. One to four colored squares are shown for 100 ms. After a delay, they reappear and the task is to click on the one square that has changed color (50% chance). Performance is expressed as the percentage of correct responses.
Time frame: baseline (week 1) and post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Change in Working Memory Capacity | Baseline | 67.7 percentage correct responses | Standard Deviation 16 |
| Cognitive Remediation Training With Nicotine | Change in Working Memory Capacity | Post-intervention (10 weeks) | 67.2 percentage correct responses | Standard Deviation 13.7 |
| Cognitive Remediation Training Without Nicotine | Change in Working Memory Capacity | Baseline | 67.5 percentage correct responses | Standard Deviation 14.5 |
| Cognitive Remediation Training Without Nicotine | Change in Working Memory Capacity | Post-intervention (10 weeks) | 68.6 percentage correct responses | Standard Deviation 13.7 |
Secondary
Cognitive Assessment Interview (CAI) Score
Clinician-administered interview about daily life cognitive functioning. The CAI assesses 10 items related to working memory, attention/vigilance, learning/memory, problem solving, processing speed, and social cognition. The total score ranges from 1 (inability to maintain personal hygiene due to cognitive deficits) to 100 (superior cognitive functioning in a wide range of activities). A score of 55 corresponds to moderate cognitive symptoms, e.g. persistent problems paying attention or forgetting scheduled events.
Time frame: baseline (week 0) and post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Cognitive Assessment Interview (CAI) Score | Baseline | 55.80 score on a scale | Standard Deviation 12.88 |
| Cognitive Remediation Training With Nicotine | Cognitive Assessment Interview (CAI) Score | Post-intervention (week 10) | 69.30 score on a scale | Standard Deviation 12.52 |
| Cognitive Remediation Training Without Nicotine | Cognitive Assessment Interview (CAI) Score | Baseline | 59.14 score on a scale | Standard Deviation 9.59 |
| Cognitive Remediation Training Without Nicotine | Cognitive Assessment Interview (CAI) Score | Post-intervention (week 10) | 64.79 score on a scale | Standard Deviation 10.69 |
Secondary
Scale for the Assessment of Negative Symptoms (SANS) Score
Clinician rating scale of negative symptoms in schizophrenia. Within each of 5 domains, separate symptoms are rated from 0 (absent) to 5 (severe). Total scores are the sum of 22 subscales and range from 0 to 110, with larger values reflecting higher negative symptoms.
Time frame: baseline (week 0), post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Scale for the Assessment of Negative Symptoms (SANS) Score | Baseline | 36.40 score on a scale | Standard Deviation 11.64 |
| Cognitive Remediation Training With Nicotine | Scale for the Assessment of Negative Symptoms (SANS) Score | Post-intervention (10 weeks) | 33.80 score on a scale | Standard Deviation 12.14 |
| Cognitive Remediation Training Without Nicotine | Scale for the Assessment of Negative Symptoms (SANS) Score | Baseline | 37.73 score on a scale | Standard Deviation 7.09 |
| Cognitive Remediation Training Without Nicotine | Scale for the Assessment of Negative Symptoms (SANS) Score | Post-intervention (10 weeks) | 36.53 score on a scale | Standard Deviation 7.04 |
Secondary
Training Exercise Parameters: Visual and Sound Sweeps
Some of the Posit Science exercises provide an assessment tool of training progress on task parameters, which adjust continuously to keep performance at \ 85% correct. Enhanced sensory processing speed and precision is considered the central building block of training benefits. Therefore, we analyzed the two exercises aimed at training these processes. Performance is quantified as stimulus presentation time in ms of visual or sound sweeps, which the participant has to judge in terms of change across space or time. Smaller values reflect better performance. Visual and sound sweeps were averaged.
Time frame: baseline (week 0), post-intervention (week 10), 4-week follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | Baseline | 130.25 ms | Standard Deviation 46.26 |
| Cognitive Remediation Training With Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | Week 10 (end-of-treatment) | 94.40 ms | Standard Deviation 28.04 |
| Cognitive Remediation Training With Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | 4-week follow-up | 102.80 ms | Standard Deviation 39.45 |
| Cognitive Remediation Training Without Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | Baseline | 198.80 ms | Standard Deviation 159.16 |
| Cognitive Remediation Training Without Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | Week 10 (end-of-treatment) | 124.40 ms | Standard Deviation 73.03 |
| Cognitive Remediation Training Without Nicotine | Training Exercise Parameters: Visual and Sound Sweeps | 4-week follow-up | 117.50 ms | Standard Deviation 69.76 |
Secondary
UCSD Performance-Based Skills Assessment (UPSA) Score
Measures ability to perform real-life tasks by standardized role-play. Scores reflect percent correct, i.e. range from 0-100 with higher scores representing better performance.
Time frame: baseline (week 0) and post-intervention (week 10)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cognitive Remediation Training With Nicotine | UCSD Performance-Based Skills Assessment (UPSA) Score | Baseline | 77.50 score on a scale | Standard Deviation 14.97 |
| Cognitive Remediation Training With Nicotine | UCSD Performance-Based Skills Assessment (UPSA) Score | Post-intervention (week 10_ | 75.50 score on a scale | Standard Deviation 14.55 |
| Cognitive Remediation Training Without Nicotine | UCSD Performance-Based Skills Assessment (UPSA) Score | Baseline | 71.87 score on a scale | Standard Deviation 14.01 |
| Cognitive Remediation Training Without Nicotine | UCSD Performance-Based Skills Assessment (UPSA) Score | Post-intervention (week 10_ | 74.00 score on a scale | Standard Deviation 12.28 |