Schizophrenia
Conditions
Brief summary
Impairments in social integration, characterized by low marriage rates, few friendships, and a high frequency of living alone, affect the vast majority of Veterans with schizophrenia. The primary aim of this proposal is to test the efficacy of a novel rehabilitation treatment approach, engaging in physical exercise, at improving two determinants of social integration which are impaired in schizophrenia: cognition and affect.
Detailed description
Difficulties in social integration pose a major mental health problem for Veterans with schizophrenia. Reviews of the literature indicate that Veterans with schizophrenia have lower marriage rates, fewer friendships, and higher rates of living alone than the general population. Poor social integration is also associated with early mortality. To gain traction on this problem, it will be necessary to find treatments that address key determinants of social integration. Evidence indicates that impairments in cognition and affect are among the key determinants of this area of functioning. Findings from the broader rehabilitation literature support a novel conceptual approach to this problem, namely engagement in physical exercise. Physical exercise is associated with improvements in attention, episodic memory, working memory, speed of processing, and executive control. In addition, physical exercise is associated with increases in positive affect and decreases in negative affect. Findings on the effects of physical exercise on cognition and affect have been reported for normal aging, mild cognitive impairment, neurodegenerative disorders, oncology, and depression, but is an area of investigation relatively new to schizophrenia. The proposed study will include 54 Veterans with schizophrenia or schizoaffective disorder (aged 45-65) who will be matched on baseline levels of cardiorespiratory fitness, and then randomized (2:1) to a walking exercise group (n=36) or a control comparison group (n=18). Veterans in the exercise group will participate in a 12-week, instructor-led, outdoor brisk walking exercise program conducted in small groups (n=6), held 3 times per week, gradually increasing walking time until reaching a maximum of 40-minutes per session. The heart rate of each Veteran will be monitored during the walking sessions to help ensure maintenance of a target peak heart rate of 60% to 70% of the maximum for the individual's age (i.e., 220-age). Veterans in the control group will participate in instructor-led, non-aerobic stretching exercises in small groups (n=6) with the duration, frequency, and total number of sessions matched to the exercise group. Primary outcome measures of cardiorespiratory fitness, cognition, and positive and negative affect of participants in both groups will be measured at baseline and the 12-week end-point assessment.
Interventions
BEHAVIORALPhysical exercise
Veterans in the physical exercise group will participate in a 12-week, instructor-led, outdoor brisk walking exercise program conducted in small groups, held 3 times per week, gradually increasing walking time until reaching a maximum of 40-minutes per session. The heart rate of each Veteran will be monitored during the walking sessions to help ensure maintenance of a target peak heart rate of 60% to 70% of the maximum for the individual's age (i.e., 220-age).
BEHAVIORALStretching exercise
Veterans in the control condition will participate in instructor-led, non-aerobic stretching exercises conducted in small groups, held 3 times per week.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnostic and Statistical Manual (DSM) - 5 diagnosis of schizophrenia or schizoaffective disorder; * age 40-65; * screened for physical health risks (i.e., no serious heart condition, dizziness, bone or joint problems posing safety concerns, ambulatory limitations); * clinically stable (e.g., no inpatient hospitalizations for 3 months prior to enrollment; no change in type of antipsychotic medication in the past 4 weeks)
Exclusion criteria
* evidence of alcohol or substance use disorder (moderate or greater severity) per DSM-5 criteria in the past 3 months; * clinically significant neurological disease as determined by medical history (e.g., seizure disorder); * history of serious head injury with loss of consciousness \>1 hour; * participation in an exercise program within past 6 months; * not able to understand spoken and written English sufficiently to comprehend consent procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Score From Non-social Cognition Battery | Change from baseline to the 12-week endpoint assessment | Raw scores (i.e., total scores) for the following tests will be transformed to z-scores: attention (CPT-IP), speed of processing (BACS symbol coding), working memory (WAIS-IV letter-number sequencing test), verbal learning (Hopkins Verbal Learning Test - Revised), and executive control (AX-CPT). The outcome measure is the mean z-score. The composite z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean of the overall sample of study participants. Negative numbers indicate values lower than other study participants and positive numbers indicate values higher than other study participants. |
| Total Score for Social Functioning | Change from baseline to 12 week endpoint assessment | Birchwood Social Functioning Scale is a measure of social functioning. The total score for social functioning is calculated by summing the raw scores from each of the seven subscales (social engagement, interpersonal communication, independence - performance, independence - competence, recreation, prosocial behavior, employment); possible range is 0 to 223 with higher scores representing better social functioning. |
| Total Score for Speed of Processing (i.e., Cognition) as Assessed by the Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Coding Test | Change from baseline to 12-week endpoint assessment | Brief Assessment of Cognition in Schizophrenia (BACS) is a measure of speed of information processing. The total score for speed of processing (i.e., cognition) is calculated by summing the number of symbol-code pairs completed correctly on the BACS Symbol Coding test within the allotted 90 second time limit. Scores range from 0 to 110 with higher scores representing better information processing speed. |
| Total Score for Positive Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | Change from baseline to the 12-week endpoint assessment | Positive and Negative Affect Scale is a measure of an individual's positive and negative affect. The scale includes 32 items; 16 denote positive affect and 16 denote negative affect. Each item is rated on a scale of 1 (very slightly or not at all) to 5 (extremely). The total score for PANAS positive affect is calculated by summing the ratings for items denoting positive affect. Scores range from 16 to 80; higher scores represent better positive affect. |
| Total Score for Negative Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | Change from baseline to the 12-week endpoint assessment | Positive and Negative Affect Scale is a measure of an individual's positive and negative affect. The scale includes 32 items; 16 denote positive affect and 16 denote negative affect. Each item is rated on a scale of 1 (very slightly or not at all) to 5 (extremely). The total score for PANAS negative affect is calculated by summing the ratings for items denoting negative affect. Scores range from 16 to 80; lower scores represent better levels of negative affect. |
| VO2max | Change from baseline to 12-week endpoint assessment | Measure of aerobic capacity (VO2max) is derived by using a regression formula based on age, weight, sex, and time to complete walking of one mile. Because scores are derived using a regression equation, there is no absolute minimum or maximum value; higher scores represent better aerobic capacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BDNF Value | Change from baseline to the 12-week endpoint assessment | BDNF concentration will be quantified by enzyme-linked immunosorbent assay (R&D Systems). The value will be expressed in ng/ml. |
| Positive Symptom Subscale Score From the BPRS | Change from baseline to the 12-week endpoint assessment | The Brief Psychiatric Rating Scale (BPRS) is a measure of psychiatric symptom severity and includes subscale scores for positive and negative symptoms. The outcome score for positive symptoms is calculated by summing the ratings for items measuring hallucinations, unusual thought content, and conceptual disorganization; each item is rated on a scale of 1 to 7 with higher scores indicating greater symptom severity; possible range for positive symptoms is 0 to 21 with higher scores representing greater severity of positive symptoms. |
| Negative Symptom Subscale Score From the BPRS | Change from baseline to the 12-week endpoint assessment | The Brief Psychiatric Rating Scale (BPRS) is a measure of psychiatric symptom severity and includes subscale scores for positive and negative symptoms. The outcome score for negative symptoms is calculated by summing the ratings for items measuring blunted affect, emotional withdrawal, and motor retardation; each item is rated on a scale of 1 to 7 with higher scores indicating greater symptom severity; possible range for negative symptoms is 0 to 21 with higher scores representing greater severity of negative symptoms. |
| Composite Score From Social Cognition Battery | Change from baseline to the 12-week endpoint assessment | Raw scores (i.e., total scores) for the following tests will be transformed to z-scores: emotion perception (Facial Emotion Identification Test), social perception (Half-Profile of Nonverbal Sensitivity; PONS), theory of mind (The Awareness of Social Inference Test; TASIT - Part 2), empathy (empathic accuracy test). The outcome measure is the mean z-score. The composite z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean of the overall sample of study participants. Negative numbers indicate values lower than other study participants and positive numbers indicate values higher than other study participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Physical Exercise Participants participate in brisk walking exercises.
Physical exercise: Veterans in the physical exercise group will participate in a 12-week, instructor-led, outdoor brisk walking exercise program conducted in small groups, held 3 times per week, gradually increasing walking time until reaching a maximum of 40-minutes per session. The heart rate of each Veteran will be monitored during the walking sessions to help ensure maintenance of a target peak heart rate of 60% to 70% of the maximum for the individual's age (i.e., 220-age). | 35 |
| Stretching Exercise Participants participate in non-aerobic, non-Yoga stretching exercises
Stretching exercise: Veterans in the control condition will participate in instructor-led, non-aerobic stretching exercises conducted in small groups, held 3 times per week. | 18 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 5 |
Baseline characteristics
| Characteristic | Physical Exercise | Stretching Exercise | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 6.2 | 55.7 years STANDARD_DEVIATION 7.1 | 56.1 years STANDARD_DEVIATION 6.5 |
| Birchwood Social Functioning Scale | 121.0 units on a scale STANDARD_DEVIATION 24.7 | 116.7 units on a scale STANDARD_DEVIATION 22.1 | 119.5 units on a scale STANDARD_DEVIATION 23.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 12 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 8 Participants | 6 Participants | 14 Participants |
| Region of Enrollment United States | 35 participants | 18 participants | 53 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 33 Participants | 18 Participants | 51 Participants |
| VO2max | 22.6 ml.kg-1.min-1 STANDARD_DEVIATION 15.3 | 23.3 ml.kg-1.min-1 STANDARD_DEVIATION 12.4 | 22.8 ml.kg-1.min-1 STANDARD_DEVIATION 14.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 18 |
| other Total, other adverse events | 0 / 35 | 0 / 18 |
| serious Total, serious adverse events | 0 / 35 | 0 / 18 |
Outcome results
Primary
Composite Score From Non-social Cognition Battery
Raw scores (i.e., total scores) for the following tests will be transformed to z-scores: attention (CPT-IP), speed of processing (BACS symbol coding), working memory (WAIS-IV letter-number sequencing test), verbal learning (Hopkins Verbal Learning Test - Revised), and executive control (AX-CPT). The outcome measure is the mean z-score. The composite z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean of the overall sample of study participants. Negative numbers indicate values lower than other study participants and positive numbers indicate values higher than other study participants.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Composite Score From Non-social Cognition Battery | .01 z-score | Standard Deviation 0.5 |
| Stretching Exercise | Composite Score From Non-social Cognition Battery | .06 z-score | Standard Deviation 0.52 |
p-value: 0.57ANCOVA
Primary
Total Score for Negative Affect as Assessed by the Positive and Negative Affect Scale (PANAS)
Positive and Negative Affect Scale is a measure of an individual's positive and negative affect. The scale includes 32 items; 16 denote positive affect and 16 denote negative affect. Each item is rated on a scale of 1 (very slightly or not at all) to 5 (extremely). The total score for PANAS negative affect is calculated by summing the ratings for items denoting negative affect. Scores range from 16 to 80; lower scores represent better levels of negative affect.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Total Score for Negative Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | 3.8 score on a scale | Standard Deviation 8.8 |
| Stretching Exercise | Total Score for Negative Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | 2.6 score on a scale | Standard Deviation 6.5 |
p-value: 0.62ANCOVA
p-value: 0.23ANCOVA
Primary
Total Score for Positive Affect as Assessed by the Positive and Negative Affect Scale (PANAS)
Positive and Negative Affect Scale is a measure of an individual's positive and negative affect. The scale includes 32 items; 16 denote positive affect and 16 denote negative affect. Each item is rated on a scale of 1 (very slightly or not at all) to 5 (extremely). The total score for PANAS positive affect is calculated by summing the ratings for items denoting positive affect. Scores range from 16 to 80; higher scores represent better positive affect.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Total Score for Positive Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | -5.6 score on a scale | Standard Deviation 12.6 |
| Stretching Exercise | Total Score for Positive Affect as Assessed by the Positive and Negative Affect Scale (PANAS) | -8.9 score on a scale | Standard Deviation 14.1 |
p-value: 0.73ANCOVA
p-value: 0.33ANCOVA
Primary
Total Score for Social Functioning
Birchwood Social Functioning Scale is a measure of social functioning. The total score for social functioning is calculated by summing the raw scores from each of the seven subscales (social engagement, interpersonal communication, independence - performance, independence - competence, recreation, prosocial behavior, employment); possible range is 0 to 223 with higher scores representing better social functioning.
Time frame: Change from baseline to 12 week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Total Score for Social Functioning | 3.7 score on a scale | Standard Deviation 10.9 |
| Stretching Exercise | Total Score for Social Functioning | -2.5 score on a scale | Standard Deviation 10.2 |
p-value: 0.06ANCOVA
Primary
Total Score for Speed of Processing (i.e., Cognition) as Assessed by the Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Coding Test
Brief Assessment of Cognition in Schizophrenia (BACS) is a measure of speed of information processing. The total score for speed of processing (i.e., cognition) is calculated by summing the number of symbol-code pairs completed correctly on the BACS Symbol Coding test within the allotted 90 second time limit. Scores range from 0 to 110 with higher scores representing better information processing speed.
Time frame: Change from baseline to 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Total Score for Speed of Processing (i.e., Cognition) as Assessed by the Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Coding Test | -0.4 score on a scale | Standard Deviation 4.9 |
| Stretching Exercise | Total Score for Speed of Processing (i.e., Cognition) as Assessed by the Brief Assessment of Cognition in Schizophrenia (BACS) Symbol Coding Test | 2.3 score on a scale | Standard Deviation 5.4 |
p-value: 0.13ANCOVA
Primary
VO2max
Measure of aerobic capacity (VO2max) is derived by using a regression formula based on age, weight, sex, and time to complete walking of one mile. Because scores are derived using a regression equation, there is no absolute minimum or maximum value; higher scores represent better aerobic capacity.
Time frame: Change from baseline to 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | VO2max | 4.0 ml.kg-1.min-1 | Standard Deviation 4 |
| Stretching Exercise | VO2max | 0.2 ml.kg-1.min-1 | Standard Deviation 5.6 |
Comparison: Data were analyzed using a 2 (groups) x 2 (time: baseline, endpoint) repeated measures ANCOVA with number of exercise sessions attended as a covariate.p-value: 0.02ANCOVA
Secondary
BDNF Value
BDNF concentration will be quantified by enzyme-linked immunosorbent assay (R&D Systems). The value will be expressed in ng/ml.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | BDNF Value | -1.04 ng/ml | Standard Deviation 9.57 |
| Stretching Exercise | BDNF Value | -7.31 ng/ml | Standard Deviation 8.01 |
p-value: 0.07ANCOVA
Secondary
Composite Score From Social Cognition Battery
Raw scores (i.e., total scores) for the following tests will be transformed to z-scores: emotion perception (Facial Emotion Identification Test), social perception (Half-Profile of Nonverbal Sensitivity; PONS), theory of mind (The Awareness of Social Inference Test; TASIT - Part 2), empathy (empathic accuracy test). The outcome measure is the mean z-score. The composite z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean of the overall sample of study participants. Negative numbers indicate values lower than other study participants and positive numbers indicate values higher than other study participants.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Composite Score From Social Cognition Battery | .06 z-score | Standard Deviation 0.46 |
| Stretching Exercise | Composite Score From Social Cognition Battery | -.17 z-score | Standard Deviation 0.47 |
p-value: 0.12ANCOVA
Secondary
Negative Symptom Subscale Score From the BPRS
The Brief Psychiatric Rating Scale (BPRS) is a measure of psychiatric symptom severity and includes subscale scores for positive and negative symptoms. The outcome score for negative symptoms is calculated by summing the ratings for items measuring blunted affect, emotional withdrawal, and motor retardation; each item is rated on a scale of 1 to 7 with higher scores indicating greater symptom severity; possible range for negative symptoms is 0 to 21 with higher scores representing greater severity of negative symptoms.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Negative Symptom Subscale Score From the BPRS | 0.1 score on a scale | Standard Deviation 2.5 |
| Stretching Exercise | Negative Symptom Subscale Score From the BPRS | 0.1 score on a scale | Standard Deviation 2.8 |
p-value: 0.86ANCOVA
Secondary
Positive Symptom Subscale Score From the BPRS
The Brief Psychiatric Rating Scale (BPRS) is a measure of psychiatric symptom severity and includes subscale scores for positive and negative symptoms. The outcome score for positive symptoms is calculated by summing the ratings for items measuring hallucinations, unusual thought content, and conceptual disorganization; each item is rated on a scale of 1 to 7 with higher scores indicating greater symptom severity; possible range for positive symptoms is 0 to 21 with higher scores representing greater severity of positive symptoms.
Time frame: Change from baseline to the 12-week endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Exercise | Positive Symptom Subscale Score From the BPRS | -1.2 score on a scale | Standard Deviation 4.5 |
| Stretching Exercise | Positive Symptom Subscale Score From the BPRS | -1.2 score on a scale | Standard Deviation 1.5 |
p-value: 0.88ANCOVA