SchizophreniaNCT03818516
Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia
A study testing Oral Glucose Tolerance Test (OGTT) in people with Schizophrenia, run by Emory University at 6 sites in United States.
Trial summary
This study will recruit persons with schizophrenia or schizoaffective disorder and will use an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Oral Glucose Tolerance Test (OGTT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesUnited States
- Study dates
- 31 Aug 2020to 1 Mar 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Willing and able to give written informed consent
- A primary diagnosis of schizophrenia, per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), or schizoaffective disorder as diagnosed by the Mini International Neuropsychiatric Interview (MINI) 7.0
- Mini Mental Status Examination Score ≥24
- Brief Negative Symptom Scale Score ≥25
- No psychotropic medication changes for one month prior to study enrollment; may be taking other psychotropic non-antipsychotic medications (i.e., antidepressants, mood stabilizers, benzodiazepines)
Who cannot join
- Evidence of untreated or poorly controlled endocrine, thyroid, cardiovascular, hematological, renal, neurological disease, hepatitis B or C or HIV
- Current HbA1C ≥ 8.5%
- Prior treatment with antiviral or immunomodulatory drugs, including corticosteroids within six months of study entry
- Current treatment with antibiotics
- Primary diagnosis of major depressive disorder or bipolar disorder
- Active abuse of alcohol or illicit/prescription drugs within the past 6 months including a urine toxicology screen positive for drugs of abuse (patients may still be included with a positive tetrahydrocannabinol (THC) result at the discretion of the PI)
Show all 14Show fewer
- Predominant left-handedness excluded for portions of the MRI scan
- Wide Range Achievement Test-3 Reading Scale (WRAT-3) score indicating less than 8th grade reading level, unless otherwise approved by the PI or PI's designee
- Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol
- History of central nervous system trauma or active seizure disorder requiring medication
- Positive pregnancy test
- Presence of metal in the body (excludes from MRI scan only)
- Active suicidal ideation as determined by the PI and/or study staff
- Diagnosis of diabetes mellitus
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Emory University Department of Psychiatry and Behavioral Sciences
Atlanta, Georgia, 30030
Grady Health System (non-CRN), Grady Health System (CRN), Ponce Center
Atlanta, Georgia, 30303
Emory Clinic, Emory University Hospital
Atlanta, Georgia, 30322
Emory University Clinical Research Network
Atlanta, Georgia, 30322
Emory University
Atlanta, Georgia, 30322
Emory Universtiy
Atlanta, Georgia, 30322
About this study
This study will recruit persons with schizophrenia or schizoaffective disorder and will use an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation.
Read the detailed description
Schizophrenia is a severe mental illness that affects 1% of the population, but accounts for over $60 billion in costs to the national healthcare system. Negative symptoms of schizophrenia, including motivational deficits, are some of the most debilitating aspects of the disorder, being both difficult to treat and representing one of the most significant barriers to functional recovery. One pathophysiologic pathway that may contribute to these alterations in reward circuitry in schizophrenia is inflammation. Increased inflammation has been reliably linked to deficits in reward processing and decreased motivation via effects of inflammatory cytokines on regions of the basal ganglia, including the ventral striatum. Previous findings show that some patients with schizophrenia reliably exhibit elevated concentrations of inflammatory markers and that inflammatory cytokines may be related to negative symptoms including decreased motivation. Relevant to the impact of inflammation on insulin signaling, measures of insulin sensitivity are significantly worse in patients with schizophrenia, including at illness onset. Moreover, antipsychotic medications lead to metabolic syndrome, contributing to risk for insulin resistance and ultimately diabetes. Insulin resistance is believed to be caused by increased inflammation, and in turn can contribute to inflammation through alterations in glucose metabolism.
This study uses an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation. The researchers will recruit subjects with a range of insulin resistance, as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This will allow the researchers to investigate the contributions of metabolic dysfunction and inflammation on inflammatory and metabolic markers, brain reward circuitry, motivational deficits, and negative symptoms.
- Conditions
- Schizophrenia
- Being tested
- Oral Glucose Tolerance Test (OGTT)
- Keywords
- Inflammation, Magnetic Resonance Imaging (MRI), Negative Symptoms
- Medical subject headings
- Schizophrenia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose Tolerance Test (OGTT)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Experimental | Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test. Receives: Other: Oral Glucose Tolerance Test (OGTT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effort-Expenditure for Rewards Task (EEfRT) Score
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.
Measured: Baseline, Hour 1
Secondary outcomes (4)
Finger Tapping Task (FTT) Score
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.
Measured: Baseline, Hour 1
Trail Making Test Part A (TMT-A) Score
The 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.
Measured: Baseline, Hour 1
Digit Symbol Substitution Task (DSST) Score
The 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.
Measured: Baseline, Hour 1
Profile of Mood States (POMS) Brief Score
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.
Measured: Baseline, Hour 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2019
- Study start31 Aug 2020
- Primary completion1 Mar 2022
- Study completion1 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, David Goldsmith, Emory University
- Investigators
- David Goldsmith, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03818516
- Sponsor's protocol ID
- IRB00094972
- Other IDs
- 1K23MH114037-01A1
- Status last verified
- Apr 2024
- First submitted
- 19 Jan 2019
- Last updated
- 2 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia
- ClinicalTrials.gov ID
- NCT03818516
- Acronym / sponsor ID
- IRB00094972
- Conditions
- Schizophrenia
- Keywords
- Inflammation, Magnetic Resonance Imaging (MRI), Negative Symptoms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 1 Mar 2022 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 28 Jan 2019 (actual)
- Results
- Posted 2 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will recruit persons with schizophrenia or schizoaffective disorder and will use an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation.
Detailed description
Schizophrenia is a severe mental illness that affects 1% of the population, but accounts for over $60 billion in costs to the national healthcare system. Negative symptoms of schizophrenia, including motivational deficits, are some of the most debilitating aspects of the disorder, being both difficult to treat and representing one of the most significant barriers to functional recovery. One pathophysiologic pathway that may contribute to these alterations in reward circuitry in schizophrenia is inflammation. Increased inflammation has been reliably linked to deficits in reward processing and decreased motivation via effects of inflammatory cytokines on regions of the basal ganglia, including the ventral striatum. Previous findings show that some patients with schizophrenia reliably exhibit elevated concentrations of inflammatory markers and that inflammatory cytokines may be related to negative symptoms including decreased motivation. Relevant to the impact of inflammation on insulin signaling, measures of insulin sensitivity are significantly worse in patients with schizophrenia, including at illness onset. Moreover, antipsychotic medications lead to metabolic syndrome, contributing to risk for insulin resistance and ultimately diabetes. Insulin resistance is believed to be caused by increased inflammation, and in turn can contribute to inflammation through alterations in glucose metabolism.
This study uses an oral glucose tolerance test to test the hypothesis that insulin resistance drives inflammation. The researchers will recruit subjects with a range of insulin resistance, as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This will allow the researchers to investigate the contributions of metabolic dysfunction and inflammation on inflammatory and metabolic markers, brain reward circuitry, motivational deficits, and negative symptoms.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Glucose Tolerance Test (OGTT) | Experimental | Other: Oral Glucose Tolerance Test (OGTT)Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test. |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Willing and able to give written informed consent
- A primary diagnosis of schizophrenia, per the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), or schizoaffective disorder as diagnosed by the Mini International Neuropsychiatric Interview (MINI) 7.0
- Mini Mental Status Examination Score ≥24
- Brief Negative Symptom Scale Score ≥25
- No psychotropic medication changes for one month prior to study enrollment; may be taking other psychotropic non-antipsychotic medications (i.e., antidepressants, mood stabilizers, benzodiazepines)
Key exclusion criteria (14 listed)
- Evidence of untreated or poorly controlled endocrine, thyroid, cardiovascular, hematological, renal, neurological disease, hepatitis B or C or HIV
- Current HbA1C ≥ 8.5%
- Prior treatment with antiviral or immunomodulatory drugs, including corticosteroids within six months of study entry
- Current treatment with antibiotics
- Primary diagnosis of major depressive disorder or bipolar disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Oral Glucose Tolerance Test (OGTT) |
Primary outcome
Effort-Expenditure for Rewards Task (EEfRT) Score
Time frame: Baseline, Hour 1
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.
4 secondary outcomes
Finger Tapping Task (FTT) Score
Time frame: Baseline, Hour 1
Trail Making Test Part A (TMT-A) Score
Time frame: Baseline, Hour 1
Digit Symbol Substitution Task (DSST) Score
Time frame: Baseline, Hour 1
Profile of Mood States (POMS) Brief Score
Time frame: Baseline, Hour 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Goldsmith, MD principal investigator
Emory University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral Glucose Tolerance Test (OGTT) in people with Schizophrenia, run by Emory University at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effort-Expenditure for Rewards Task (EEfRT) Score (time frame: Baseline, Hour 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.