Trial Outcomes & Findings for Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia (NCT NCT03818516)
NCT ID: NCT03818516
Last Updated: 2024-05-02
Results Overview
EEfRT is a multitrial game task assessing motivation in which participants choose between 2 different task difficulty levels to obtain monetary rewards. For all trials, participants make repeated manual button presses which raises the level of a virtual ''bar'' viewed onscreen by the participant. Participants are eligible to win the money allotted for each trial if they raise the bar to the ''top''. Each trial presents subjects with a choice between 'high effort' and 'low effort' tasks that require different amounts of button pressing. Reward magnitudes for the high-effort task vary between amounts, while reward magnitudes for the low-effort task remain constant. Trials also vary in terms of 3 levels of probability of winning the amount associated with the choice selected. The first 50 trials are used for analysis. Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation.
COMPLETED
NA
12 participants
Baseline, Hour 1
2024-05-02
Participant Flow
Participants were recruited from Grady Health System in Atlanta, Georgia, USA. Participant enrollment began August 31, 2020, and all follow-up was complete by March 1, 2022.
This was an optional substudy underpowered to identify relationships between changes in inflammatory and metabolic markers pre- and post-OGTT with reward circuitry or motivational deficits. These analyses are thus exploratory and would serve as preliminary data for future research proposals.
Participant milestones
| Measure |
Oral Glucose Tolerance Test (OGTT)
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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|---|---|
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Overall Study
STARTED
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12
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Overall Study
COMPLETED
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11
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Oral Glucose Tolerance Test (OGTT)
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Overall Study
Exclusion due to positive UDS (THC) test
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1
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Baseline Characteristics
Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia
Baseline characteristics by cohort
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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11 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
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35.36 years
STANDARD_DEVIATION 12.42 • n=5 Participants
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Sex: Female, Male
Female
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1 Participants
n=5 Participants
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Sex: Female, Male
Male
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10 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
United States
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11 participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline, Hour 1EEfRT is a multitrial game task assessing motivation in which participants choose between 2 different task difficulty levels to obtain monetary rewards. For all trials, participants make repeated manual button presses which raises the level of a virtual ''bar'' viewed onscreen by the participant. Participants are eligible to win the money allotted for each trial if they raise the bar to the ''top''. Each trial presents subjects with a choice between 'high effort' and 'low effort' tasks that require different amounts of button pressing. Reward magnitudes for the high-effort task vary between amounts, while reward magnitudes for the low-effort task remain constant. Trials also vary in terms of 3 levels of probability of winning the amount associated with the choice selected. The first 50 trials are used for analysis. Percentage of hard-task choices across all levels of probability is calculated from all hard choices. Lower percentages of hard task choices indicate decreased motivation.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Effort-Expenditure for Rewards Task (EEfRT) Score
Baseline
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0.268 proportion of hard-task choices
Standard Deviation 0.217
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Effort-Expenditure for Rewards Task (EEfRT) Score
Hour 1
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0.189 proportion of hard-task choices
Standard Deviation 0.153
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SECONDARY outcome
Timeframe: Baseline, Hour 1Population: 11 participants analyzed for baseline, but only 10 completed the 1-hour measurements. One participant could not complete the tasks for the left hand.
The Finger Tapping Task (FTT) uses a specially adapted tapper that the subject is asked to tap as fast as possible. The subject is given 5 consecutive 10-second trials for the preferred and non-preferred hands.The FTT is design to assess subtle motor impairment and found to be altered in subjects with basal ganglia disorders and lesions. The finger tapping score is the mean number of taps of 5 trials and is computed for each hand.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Finger Tapping Task (FTT) Score
Left hand- Hour 1
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42.01 number of taps on a 10 second counter
Standard Deviation 6.40
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Finger Tapping Task (FTT) Score
Right Hand Baseline
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44.22 number of taps on a 10 second counter
Standard Deviation 6.74
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Finger Tapping Task (FTT) Score
Right Hand- Hour 1
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42.68 number of taps on a 10 second counter
Standard Deviation 11.44
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Finger Tapping Task (FTT) Score
Left hand Baseline
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39.98 number of taps on a 10 second counter
Standard Deviation 10.91
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SECONDARY outcome
Timeframe: Baseline, Hour 1The Trail Making Test-A is a timed task that provides information on motor function and speed of processing. In Part A of the TMT participants connect circles labeled with numbers, in ascending order. The score is the amount of time it takes for the participant to complete the task. The average time it takes to complete the task is 29 seconds and times longer than 78 seconds suggest a deficiency.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Trail Making Test Part A (TMT-A) Score
Baseline
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38.86 Seconds
Standard Deviation 15.44
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Trail Making Test Part A (TMT-A) Score
Hour 1
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37.02 Seconds
Standard Deviation 16.12
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SECONDARY outcome
Timeframe: Baseline, Hour 1The DSST is a subtest of the Wechsler Adult Intelligence Scale and involves graphimotor speed, visual scanning and memory, with about half of the variance being accounted for by graphimotor speed, a third by visual scanning and 4-5% by memory. Performance on the Digit Symbol Test has been found to correlate with subcortical (caudate) atrophy in disorders involving the basal ganglia. Respondents match symbols to numbers using a key presented at the top of the test page. The score is the number of correctly entered symbols in the given time period and higher scores indicate better performance.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Digit Symbol Substitution Task (DSST) Score
Baseline
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60.55 Number of correct entered symbols
Standard Deviation 20.28
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Digit Symbol Substitution Task (DSST) Score
Hour 1
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55.09 Number of correct entered symbols
Standard Deviation 20.98
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SECONDARY outcome
Timeframe: Baseline, Hour 1Population: Only participants with available data are included in the analysis. Baseline data was inadvertently lost and only available for two (2) participants.
The POMS is a 30-item rating scale designed to measure mood states across short periods. The POMS assess six mood factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Each item is rated on a 5-point scale where 0 = not at all and 4 = extremely. Total scores range from 0 to 120 and lower scores indicate a better state of mood.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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Profile of Mood States (POMS) Brief Score
Baseline
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37.50 Score on a scale
Standard Deviation 37.48
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Profile of Mood States (POMS) Brief Score
1 hour post
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20.27 Score on a scale
Standard Deviation 12.36
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Only baseline values were analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fasting blood glucose will be assessed to determine the impact of insulin resistance on inflammatory markers.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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|---|---|
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Fasting Blood Glucose
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94.27 mg/dL
Standard Deviation 18.78
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Only baseline values were analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fasting blood insulin will be assessed to determine the impact of insulin resistance on inflammatory markers.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=11 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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|---|---|
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Fasting Blood Insulin
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12.9 mIU/L
Standard Deviation 10.05
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hour 3Assessment of effort-based decision-making will be made using the EEfRT task adapted for fMRI. During each trial, subjects are presented with a choice between two levels of task difficulty, a High Effort option, and a Low Effort option. Unlike in the behavioral version of the task, subjects will not be required to make button presses during the scan. The reward magnitude for a No Effort option remains constant, while the reward magnitude for the High Effort option varies. Additionally, the amount of effort required for the High Effort option will vary between 20%, 50%, 80%, and 100% of the subject's maximum effort (set for each individual before the scan).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hour 3Assessment of reward anticipation will be achieved using the MID task, conducted during functional MRI (fMRI) neuroimaging. Briefly, during this task participants have the opportunity to win or lose money by making a rapid button press in response to a target visual stimulus. The primary epoch of interest is the "anticipatory delay" - a period of \~2000ms that occurs after participants have been informed how much money they can win or lose on a given trial, but prior to the presentation of the target. This epoch has repeatedly been associated with robust ventral striatal activity. Participants will complete 2 functional runs of between 50 and 200 trials each (the number of trials will be decided at the discretion of the PI), with evenly distributed reward magnitudes.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hour 1This reaction time test includes simple and choice reaction time tasks and is divided into 5 stages requiring increasingly complex chains of responses and providing a distinction between reaction (or decision) time and movement latencies. Movement times on the CANTAB reaction time task have been slowed during interferon-alpha (IFN-α) treatment and correlated with IFN-alpha-induced depression and fatigue.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: One participant did not get CRP drawn. Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Plasma CRP will be assessed to determine the impact of insulin resistance on inflammatory markers.
Outcome measures
| Measure |
Oral Glucose Tolerance Test (OGTT)
n=10 Participants
Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.
Oral Glucose Tolerance Test (OGTT): Participants will undergo a fasting blood draw for inflammatory and metabolic markers before a 75gm oral glucose tolerance test (OGTT) and at 1, 2 and 3 hours post-OGTT. Behavioral assessments will also be administered pre- and post-OGTT administration.
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|---|---|
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Plasma C-reactive Protein (CRP) Levels
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3.83 mg/L
Standard Deviation 4.67
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. MCP-1 levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-10 levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sIL-6R levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-6 levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. sTNFR2 levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Only the baseline sample was analyzed. Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1beta levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MAP Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. IL-1RA levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hours 1, 2, and 3Population: Blood samples for exploratory outcome measures were not analyzed due to lack of funding.
Fluorokine MultiAnalyte Profiling (MAP) Multiplex Human Biomarker Panels will be used to measure plasma inflammatory markers that have been found to be altered in schizophrenia. TNF-alpha levels before and after the OGTT will be examined.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Hour 3For the resting state and task-based functional connectivity analysis, whole brain, subject-level correlation maps indicating regional similarity with the striatal seed region time series will be generated and Fisher transformed to Z-score maps. In addition, data reduction strategies will be employed to address inflammatory marker collinearity in analyses combining relevant inflammatory markers. To assess the significance of correlated activity with each bilateral seed region, paired t-tests will be conducted on participants' Z-score maps, adjusted for multiple comparisons. For significant brain regions, descriptive statistics will be used to characterize the mean, standard deviation, and standard error of the Z scores.
Outcome measures
Outcome data not reported
Adverse Events
Oral Glucose Tolerance Test (OGTT)
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place