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Brain Biomarker on Inflammation Response (LPS)

Primary Purpose

Schizophrenia

Status

Not yet recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LPS

Placebo

About this trial

This is an interventional basic science trial for Schizophrenia

Eligibility Criteria

15 Years - 55 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Age 18-55
Patients must be on antipsychotic medication and clinically stable, defined as no hospitalization or major change in antipsychotic medication in the past 4 weeks
Patients must pass the ESC with score 10 or above
BMI 35 or less -

Exclusion Criteria:

History of major medical illness including, but not limited to, history of heart attack, stroke, TIA (transient ischemic attack)
History of organic brain disorders that may affect neurophysiological measurements, including seizure disorder, brain tumor, head injury with evidence of significant cognitive deterioration
DSM diagnosis of substance use disorder within 6 months except nicotine and marijuana
Prior suicide attempt or frequent suicidal ideations, or current suicidal ideation assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Women who have positive urine pregnancy tests; Women who plan to become pregnant, or are breastfeeding
Frequent (more than once) history of syncope (fainting) of unknown reason
Unable to undergo MRI scanning due to metallic devices or objects or claustrophobia
Presence of co-morbid inflammatory disorders such as rheumatoid arthritis
Presence of acute or chronic infection; have received flu or similar vaccine in the past 4 weeks
Current regular use of non-steroidal anti-inflammatory drugs or immune modifying drugs
Clinically significant abnormalities on screening laboratory tests
Blood pressure <90/60 or > 150/100, or pulse <55 or > 100 beats/minute, or temperature > 99.5°F
12-Lead ECG demonstrating QTcF >450 msec or a QRS interval >120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject's eligibility
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Sites / Locations

University of Maryland, Baltimore

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

LPS-Patient

LPS-Healthy

Placebo-Patient

Arm Description

Schizophrenia patients who are randomized to receive LPS injection.

Healthy controls who are randomized to receive LPS injection.

Schizophrenia patients who are randomized to receive placebo injection.

Outcomes

Primary Outcome Measures

IL-6

Cytokine IL-6 at baseline and response to LPS challenge (to be reported in pg/ml or IU/ml)

Secondary Outcome Measures

Brain imaging structure and function via MRI

Brain imaging at baseline and response to LPS challenge (to be reported in institutional units)

Full Information

NCT ID

NCT03271814

First Posted

August 29, 2017

Last Updated

October 10, 2022

Sponsor

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT03271814

Brief Title

Brain Biomarker on Inflammation Response

Acronym

LPS

Official Title

Brain Biomarker on Inflammation Response

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2025 (Anticipated)

Primary Completion Date

December 15, 2025 (Anticipated)

Study Completion Date

December 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In a double-blinded, randomized, parallel controlled design, patients with schizophrenia spectrum disorder will be exposed to a single dose of lipopolysaccharide (LPS) (LPS-patient). Clinical symptoms, blood samples, and brain imaging will be assessed at baseline and after LPS. There will be two comparison groups. Comparison groups include an age- and sex-matched healthy control group also exposed to the same LPS (LPS-control), and an age- and sex-matched sample of patients with schizophrenia on placebo (Placebo-patient). As in Phase I studies, multiple interim analyses are expected so the current design may be modified, which will be communicated during annual reports (21CFR312.30).

Detailed Description

Schizophrenia spectrum disorders are a major public health burden due to functional and cognitive impairment, psychosis and other symptoms, and high comorbidity. Unfortunately, current therapies have limited effectiveness in treating some of the symptoms and most of the cognitive deficits. Alternative biological models of the disease are needed for developing new and more effective treatment. Neuroinflammation has increasingly been implicated in the pathophysiology of schizophrenia. Patients with schizophrenia have signs of low-grade, chronic inflammation, including elevated blood levels of pro-inflammatory cytokines and other immune markers. Administration of LPS is the standard immune challenge to investigate the body's immune response in a wide range of disorders. Our goal is to use LPS to investigate whether schizophrenia patients have abnormal immune response to LPS and whether the abnormality is associated with specific brain imaging biomarkers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

LPS-Patient

Arm Type

Experimental

Arm Description

Schizophrenia patients who are randomized to receive LPS injection.

Arm Title

LPS-Healthy

Arm Type

Active Comparator

Arm Description

Healthy controls who are randomized to receive LPS injection.

Arm Title

Placebo-Patient

Arm Type

Placebo Comparator

Arm Description

Schizophrenia patients who are randomized to receive placebo injection.

Intervention Type

Biological

Intervention Name(s)

LPS

Intervention Description

0.6 by/kg LPS single dose iv

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Sterile Water

Primary Outcome Measure Information:

Title

IL-6

Description

Cytokine IL-6 at baseline and response to LPS challenge (to be reported in pg/ml or IU/ml)

Time Frame

Hourly for 6 hours

Secondary Outcome Measure Information:

Title

Brain imaging structure and function via MRI

Description

Brain imaging at baseline and response to LPS challenge (to be reported in institutional units)

Time Frame

3 to 6 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-55 Patients must be on antipsychotic medication and clinically stable, defined as no hospitalization or major change in antipsychotic medication in the past 4 weeks Patients must pass the ESC with score 10 or above BMI 35 or less - Exclusion Criteria: History of major medical illness including, but not limited to, history of heart attack, stroke, TIA (transient ischemic attack) History of organic brain disorders that may affect neurophysiological measurements, including seizure disorder, brain tumor, head injury with evidence of significant cognitive deterioration DSM diagnosis of substance use disorder within 6 months except nicotine and marijuana Prior suicide attempt or frequent suicidal ideations, or current suicidal ideation assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Women who have positive urine pregnancy tests; Women who plan to become pregnant, or are breastfeeding Frequent (more than once) history of syncope (fainting) of unknown reason Unable to undergo MRI scanning due to metallic devices or objects or claustrophobia Presence of co-morbid inflammatory disorders such as rheumatoid arthritis Presence of acute or chronic infection; have received flu or similar vaccine in the past 4 weeks Current regular use of non-steroidal anti-inflammatory drugs or immune modifying drugs Clinically significant abnormalities on screening laboratory tests Blood pressure <90/60 or > 150/100, or pulse <55 or > 100 beats/minute, or temperature > 99.5°F 12-Lead ECG demonstrating QTcF >450 msec or a QRS interval >120 msec. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF values should be used to determine the subject's eligibility -

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Judy Liu, RN, MSN

Phone

410-402-6832

jliu@mprc.umaryland.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Dawn R Detamore

Phone

410-402-6820

ddetamor@mprc.umaryland.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

L E Hong, M.D.

Organizational Affiliation

University of Maryland, Baltimore

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Maryland, Baltimore

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21228

Country

United States

12. IPD Sharing Statement

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Brain Biomarker on Inflammation Response

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