Peripheral Immune System in Individuals With Schizophrenia

Schizophrenia Clinical Trial

Official title:

Peripheral Immune System in Individuals With Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05109065
• Other study ID #: 58926
• Status: Recruiting
• Start date: March 1, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Stanford University
• Contact: Diane E Wakeham, PhD
• Phone: 650-736-5243
• Email: wakeham[@]stanford.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators are seeking healthy volunteers and people with schizophrenia or schizoaffective disorder for a clinical study of the immune system in psychotic disorders. This is an observational study, to understand the ways in which the immune system may be contributing to the disease process.

Description:

Genetic studies have linked the number of copies coding for C4 protein to risk for schizophrenia. Studies examining the amount of mRNA, the molecules that point to how much C4 protein is likely being made, found more C4 mRNA in the brains from individuals with schizophrenia. Studies in mice have suggested that expressing more C4 protein in the brain, specifically the A-type of C4, can result in abnormalities in behavior. However, researchers have also found that pathways that involve this protein in the blood to be abnormal in individuals even before they develop schizophrenia and hypothesize these abnormalities change the blood brain barrier. In this work, the researchers are hoping to understand the ways in which C4 protein is abnormal in the peripheral blood and how this may be contributing to the disease process in hopes of finding new ways of helping individuals with schizophrenia and possibly other mental health disorders. A major goal of this study is to collect blood tissue for ongoing translational study of pathophysiological mechanisms of schizophrenia.

Interested participants will be asked a series of questions about their medical and mental health history, be able to provide informed consent, undergo a urine toxicology screen and be willing to provide a blood sample.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria for Subjects with schizophrenia and schizoaffective disorders:

• Schizophrenia or schizoaffective disorder diagnosis verified by interview

• Diagnosis or initiation of antipsychotic medication was within last 5 years

Inclusion Criteria for Healthy Controls:

• No known diagnosis of schizophrenia or schizoaffective disorder

• No history of depression, anxiety, bipolar disorder, PTSD, agoraphobia, panic disorder, or generalized anxiety disorder

• Negative assessment for psychotic symptoms on day of interview

Exclusion Criteria (for both groups):

• Participants have a history of bleeding disorders or are taking blood thinners.

• Participants have a history of epilepsy, known genetic disorders

• Immunocompromised state (eg., receiving immunosuppressive therapy, transplant).

• History of brain-related disease (eg., stroke)

• Any uncontrolled medical disorder such as cancer.

• History of substance abuse or positive urine toxicology screen (including test for marijuana) on the day of the blood draw

Related Conditions & MeSH terms

• Mood Disorders
• Psychotic Disorders
• Schizo Affective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

Diagnostic Test:
• SCID (Standardized Clinical Interview for DSM-V)
The Structured Clinical Interview for DSM-5 (SCID-5) is a semistructured interview guide for a clinician or trained mental health professional to diagnose major mental illnesses.
• PSS (Perceived Stress Score)
The Perceived Stress Scale (PSS) is the most widely used psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. Items were designed to tap how unpredictable, uncontrollable, and overloaded respondents find their lives. Demographic information will also be collected.
• Urine Toxicology Screen
Participants will be asked to provide a urine sample. Evidence of active substance abuse (marijuana, opioids, other non-prescription drugs) by the urine toxicology screen will disqualify participants from the study.
• Vitals
Height and weight will be measured in order to calculate BMI.
• Blood Work
A venipuncture will be performed for the purpose of collecting blood tissue for study.
• PQ-B
The Prodromal Questionnaire - Brief Version (PQ-B) is a self-report measure designed to identify people who may be experiencing psychotic symptoms when they do not have a schizophrenia diagnosis.
• COVID Screening
Questionnaire to assess risk of transmission of COVID-19.
• Positive and Negative Syndrome Scale (PANSS)
Instrument that is completed by clinical interviewer to measure symptom severity in individuals with psychotic disorders.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kalinowski A, Liliental J, Anker LA, Linkovski O, Culbertson C, Hall JN, Pattni R, Sabatti C, Noordsy D, Hallmayer JF, Mellins ED, Ballon JS, O'Hara R, Levinson DF, Urban AE. Increased activation product of complement 4 protein in plasma of individuals with schizophrenia. Transl Psychiatry. 2021 Sep 22;11(1):486. doi: 10.1038/s41398-021-01583-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Group comparison of C4 protein in immune cells	Measure the concentration of complement 4 protein in immune cells.	Day 1
Secondary	Body Mass Index and its relationship to C4 protein concentration	The relationship between body mass index, calculated from the measured height and weight of participants, and the primary outcome (C4 protein concentration) will be determined.	Day 1
Secondary	C4 Gene Copy Number	Determine the C4 Gene Copy Number its relationship to C4 protein concentration in immune cells.	Day 1
Secondary	C4 Activation	Measure activity of C4 protein and its relationship to the primary outcome.	Day 1
Secondary	Relationship to symptom presentation	Explore the relationship between clinical severity scores (PANSS) and the primary outcome.	Day 1
Secondary	Relationship to stress	Explore the relationship between perceived stress (PSS) and the primary outcome.	Day 1

External Links

•   Laskaris, et.al. Schizophr Res . 2019 Feb;204:30-37.
•   Mongan, et. al. Jama Psychiatry 2021;78(1):77-90
•   Onwordi, et. al. Nat Commun . 2020 Jan 14;11(1):246.
•   Onwordi, et. al. Transl Psychiatry . 2021 Jul 17;11(1):393.
•   Radhakrishnan, et al. Mol Psychiatry . 2021 Jun 16.
•   Sekar, at al. Nature . 2016 Feb 11;530(7589):177-83.
•   Yilmaz, et. al. Nat Neurosci . 2021 Feb;24(2):214-224.