Peripheral Immune System in Individuals With Schizophrenia

• Sponsor: Stanford University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05109065
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Anticipated Duration (Months): 21
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizo Affective Disorder; Schizophreniform Disorders	Diagnostic Test: SCID (Standardized Clinical Interview for DSM-V); Diagnostic Test: PSS (Perceived Stress Score); Diagnostic Test: Urine Toxicology Screen; Diagnostic Test: Vitals; Diagnostic Test: Blood Work; Diagnostic Test: PQ-B; Diagnostic Test: COVID Screening; Diagnostic Test: Positive and Negative Syndrome Scale (PANSS)

Detailed 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.

Study Design

• Study Type: Observational
• Anticipated Enrollment: 100 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Peripheral Immune System in Individuals With Schizophrenia
• Actual Study Start Date: Mar 1, 2021
• Anticipated Primary Completion Date: Aug 31, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Individuals with primary psychotic disorders Participants who have received any of the following diagnoses: schizophrenia, schizoaffective disorder, or schizophreniform disorder. Participants will have urine toxicology screen, vitals recorded, and blood drawn in a single visit.	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.; Diagnostic Test: 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.; Diagnostic Test: 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.; Diagnostic Test: Vitals; Height and weight will be measured in order to calculate BMI.; Diagnostic Test: Blood Work; A venipuncture will be performed for the purpose of collecting blood tissue for study.; Diagnostic Test: COVID Screening; Questionnaire to assess risk of transmission of COVID-19.; Diagnostic Test: Positive and Negative Syndrome Scale (PANSS); Instrument that is completed by clinical interviewer to measure symptom severity in individuals with psychotic disorders.
Healthy Controls Healthy participants who do not have any exclusion criteria will undergo an assessment to confirm absence of psychiatric disorder. Participants will have urine toxicology screen, vitals recorded, and blood drawn in a single visit.	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.; Diagnostic Test: 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.; Diagnostic Test: 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.; Diagnostic Test: Vitals; Height and weight will be measured in order to calculate BMI.; Diagnostic Test: Blood Work; A venipuncture will be performed for the purpose of collecting blood tissue for study.; Diagnostic Test: 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.; Diagnostic Test: COVID Screening; Questionnaire to assess risk of transmission of COVID-19.

Outcome Measures

Primary Outcome Measures

1. Group comparison of C4 protein in immune cells [Day 1]

   Measure the concentration of complement 4 protein in immune cells.

Secondary Outcome Measures

1. Body Mass Index and its relationship to C4 protein concentration [Day 1]

   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.

2. C4 Gene Copy Number [Day 1]

   Determine the C4 Gene Copy Number its relationship to C4 protein concentration in immune cells.

3. C4 Activation [Day 1]

   Measure activity of C4 protein and its relationship to the primary outcome.

4. Relationship to symptom presentation [Day 1]

   Explore the relationship between clinical severity scores (PANSS) and the primary outcome.

5. Relationship to stress [Day 1]

   Explore the relationship between perceived stress (PSS) and the primary outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94704

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Agnes Kalinowski, MD/PhD, Clinical Professor of Psychiatry and Behavior Sciences

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mongan, et.al. Schizophrenia Research 2020 Aug; 222:58-72.
• Laskaris, et.al. Schizophr Res . 2019 Feb;204:30-37.
• Mongan, et. al. Jama Psychiatry 2021;78(1):77-90
• Gandal, et. al. Science 2018 Dec 14;362(6420):eaat8127.
• Yilmaz, et. al. Nat Neurosci . 2021 Feb;24(2):214-224.
• Sekar, at al. Nature . 2016 Feb 11;530(7589):177-83.
• Radhakrishnan, et al. Mol Psychiatry . 2021 Jun 16.
• Onwordi, et. al. Transl Psychiatry . 2021 Jul 17;11(1):393.
• Onwordi, et. al. Nat Commun . 2020 Jan 14;11(1):246.

Publications

• 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.

• Responsible Party: Agnieszka Kalinowski, Clinical Instructor, Stanford University
• ClinicalTrials.gov Identifier: NCT05109065
• Other Study ID Numbers: 58926
• First Posted: Nov 5, 2021
• Last Update Posted: Mar 17, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Agnieszka Kalinowski, Clinical Instructor, Stanford University: psychosis; psychiatry; complement immune system
• Additional relevant MeSH terms: Disease; Schizophrenia; Mood Disorders; Psychotic Disorders

Study Results

No Results Posted as of Mar 17, 2022