Impact of Inflammation on Reward Circuits, Motivational Deficits and Negative Symptoms in Schizophrenia

NCT03818516 | Completed Results DMC

• 2 other identifiers: IRB000949721K23MH114037-01A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Schizophrenia

Keywords

Inflammation; Magnetic Resonance Imaging (MRI); Negative Symptoms

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Hour 1

Secondary Outcomes (4)

• Finger Tapping Task (FTT) Score

  Baseline, Hour 1

• Trail Making Test Part A (TMT-A) Score

  Baseline, Hour 1

• Digit Symbol Substitution Task (DSST) Score

  Baseline, Hour 1

• Profile of Mood States (POMS) Brief Score

  Baseline, Hour 1

Other Outcomes (15)

• Fasting Blood Glucose

  Baseline, Hours 1, 2, and 3

• Fasting Blood Insulin

  Baseline, Hours 1, 2, and 3

• Neural Response to Reward Motivation Assessed by fMRI-adapted Version of the EEfRT

  Baseline, Hour 3

Study Arms (1)

Oral Glucose Tolerance Test (OGTT)

EXPERIMENTAL

Medically stable participants with schizophrenia and a range of insulin resistance will have an oral glucose tolerance test.

Other: Oral Glucose Tolerance Test (OGTT)

Interventions

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.

Oral Glucose Tolerance Test (OGTT)

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (6)

Emory University Department of Psychiatry and Behavioral Sciences

Atlanta, Georgia, 30030, United States

Location

Grady Health System (non-CRN), Grady Health System (CRN), Ponce Center

Atlanta, Georgia, 30303, United States

Location

Emory Clinic, Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory University Clinical Research Network

Atlanta, Georgia, 30322, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Emory Universtiy

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Schizophrenia; Inflammation

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Results Point of Contact

• Title: David R. Goldsmith, MD
• Organization: Emory University

drgolds@emory.edu

404-727-3735

Study Officials

• David Goldsmith, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 19, 2019
• First Posted: January 28, 2019
• Study Start: August 31, 2020
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)