Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort

NCT ID: NCT02910037

Last Updated: 2021-05-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-01

Study Completion Date

2017-07-31

Brief Summary

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This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients. From June 2016 to June 2017, 200 patients will be enrolled from multiple hospitals in California and outside of California. Patients will be evaluated to determine the impact on the mNGS assay on diagnostic yield, hospital costs and clinical outcomes.

Detailed Description

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This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients, with the goal of directly impacting clinical care and improving patient mortality. This diagnostic test has been previously validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, the University of California, San Francisco Clinical Microbiology Laboratory. From June 2016 to June 2017, investigators will prospectively enroll 200 patients from multiple hospitals in California (University of California, San Francisco; University of California, Los Angeles; University of California, Davis; Children's Hospital Los Angeles) and outside California (Children's National Medical Center, Children's Hospital Colorado, St. Jude Children's Research Hospital) for mNGS testing, and evaluate the impact on the assay on diagnostic yield, hospital costs and clinical outcomes.

Conditions

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Encephalitis Meningitis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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patients enrolled for mNGS testing

Patients with meningitis and/or encephalitis will be enrolled in this study in order to analyze the clinical utility of mNGS for pathogen detection. There is no control group for this study (Investigators will identify historical controls by retrospective chart review and clinical reimbursement documents).

Group Type EXPERIMENTAL

mNGS for pathogen detection

Intervention Type DEVICE

This assay is a laboratory-validated metagenomic test for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.

Interventions

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mNGS for pathogen detection

This assay is a laboratory-validated metagenomic test for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.

Intervention Type DEVICE

Other Intervention Names

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Sequence-Based Ultrarapid Pathogen Identification (SURPI)+ UCSF metagenomic next-generation sequencing testing

Eligibility Criteria

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Exclusion Criteria

* Patients on a 5150 or 5250 psychiatric hold
* Prisoners
* University of California employees / students or close associates of any of the key personnel on the study
* Outpatients and/or patients with chronic illness

Inclusion:

Demographic Criteria

1. Age: any (no age limit)
2. Language: any (with the use of interpreting services for obtaining consent)

For the following, the infectious syndromes include meningitis, encephalitis, fever, sepsis, and pneumonia:

Clinical Criteria

1. Hospital admission or transfer with diagnosis of an presumed infectious syndrome or clinical presentation consisting with an infectious syndrome, as defined below:

* Meningitis: fever \>38°C and abnormal imaging or CSF pleocytosis (CSF white blood cell count (WBC) \> 5 /mm\^3) +/- stiff neck, +/- headache, +/- seizure
* Encephalitis: pleocytosis and at least one of the following: altered mental status, seizures, new onset of focal neurologic findings, abnormal EEG, acute brain abnormalities on neuroimaging
2. No known diagnosis of non-infectious etiology responsible for symptoms
3. Time of enrollment: within 7 days of onset of symptoms, either initial presentation or acute exacerbation of presumed infectious syndrome.

Specimen Criteria

1. cerebrospinal fluid available within 7 days of symptom onset AND within 3 days of hospital admission or transfer unless evidence for acute exacerbation as defined by abrupt decline in clinical status, worsening pleocytosis or other laboratory parameters
2. Minimum of 600 microliters (uL) of clinical sample, stored at 4 degrees Celsius (C) no more than 5 days (ideally frozen in -70 degrees Celsius within 24 hours of collection)
3. No more than 3 freeze-thaw cycles
Minimum Eligible Age

1 Minute

Maximum Eligible Age

110 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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California Initiative to Advance Precision Medicine

OTHER

Sponsor Role collaborator

Sandler Foundation

UNKNOWN

Sponsor Role collaborator

Bowes Foundation

UNKNOWN

Sponsor Role collaborator

Charles and Helen Schwab Foundation

UNKNOWN

Sponsor Role collaborator

University of California, Davis

OTHER

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role collaborator

Children's Hospital Colorado

OTHER

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role collaborator

Children's National Research Institute

OTHER

Sponsor Role collaborator

University of California, Berkeley

OTHER

Sponsor Role collaborator

DNAnexus, Inc.

UNKNOWN

Sponsor Role collaborator

Syapse, Inc.

UNKNOWN

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Charles Y Chiu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Hannah Sample, BS

Role: STUDY_DIRECTOR

University of California, San Francisco

Locations

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University of California, Davis Medical Center

Davis, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

University of California, Los Angeles Medical Center

Los Angeles, California, United States

Site Status

University of California, San Francisco Medical Center

San Francisco, California, United States

Site Status

Children's Hospital Colordao

Denver, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

St. Jude Children's Research Hospital

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, Salamat SM, Somasekar S, Federman S, Miller S, Sokolic R, Garabedian E, Candotti F, Buckley RH, Reed KD, Meyer TL, Seroogy CM, Galloway R, Henderson SL, Gern JE, DeRisi JL, Chiu CY. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med. 2014 Jun 19;370(25):2408-17. doi: 10.1056/NEJMoa1401268. Epub 2014 Jun 4.

Reference Type BACKGROUND
PMID: 24896819 (View on PubMed)

Greninger AL, Messacar K, Dunnebacke T, Naccache SN, Federman S, Bouquet J, Mirsky D, Nomura Y, Yagi S, Glaser C, Vollmer M, Press CA, Kleinschmidt-DeMasters BK, Dominguez SR, Chiu CY. Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing. Genome Med. 2015 Dec 1;7:113. doi: 10.1186/s13073-015-0235-2.

Reference Type BACKGROUND
PMID: 26620704 (View on PubMed)

Naccache SN, Peggs KS, Mattes FM, Phadke R, Garson JA, Grant P, Samayoa E, Federman S, Miller S, Lunn MP, Gant V, Chiu CY. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin Infect Dis. 2015 Mar 15;60(6):919-23. doi: 10.1093/cid/ciu912. Epub 2015 Jan 7.

Reference Type BACKGROUND
PMID: 25572898 (View on PubMed)

Greninger AL, Naccache SN, Messacar K, Clayton A, Yu G, Somasekar S, Federman S, Stryke D, Anderson C, Yagi S, Messenger S, Wadford D, Xia D, Watt JP, Van Haren K, Dominguez SR, Glaser C, Aldrovandi G, Chiu CY. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis. 2015 Jun;15(6):671-82. doi: 10.1016/S1473-3099(15)70093-9. Epub 2015 Mar 31.

Reference Type BACKGROUND
PMID: 25837569 (View on PubMed)

Naccache SN, Federman S, Veeraraghavan N, Zaharia M, Lee D, Samayoa E, Bouquet J, Greninger AL, Luk KC, Enge B, Wadford DA, Messenger SL, Genrich GL, Pellegrino K, Grard G, Leroy E, Schneider BS, Fair JN, Martinez MA, Isa P, Crump JA, DeRisi JL, Sittler T, Hackett J Jr, Miller S, Chiu CY. A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples. Genome Res. 2014 Jul;24(7):1180-92. doi: 10.1101/gr.171934.113. Epub 2014 Jun 4.

Reference Type BACKGROUND
PMID: 24899342 (View on PubMed)

Wilson MR, Shanbhag NM, Reid MJ, Singhal NS, Gelfand JM, Sample HA, Benkli B, O'Donovan BD, Ali IK, Keating MK, Dunnebacke TH, Wood MD, Bollen A, DeRisi JL. Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing. Ann Neurol. 2015 Nov;78(5):722-30. doi: 10.1002/ana.24499. Epub 2015 Aug 24.

Reference Type BACKGROUND
PMID: 26290222 (View on PubMed)

Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S, Chiu CY. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis. N Engl J Med. 2019 Jun 13;380(24):2327-2340. doi: 10.1056/NEJMoa1803396.

Reference Type RESULT
PMID: 31189036 (View on PubMed)

Chiu CY, Coffey LL, Murkey J, Symmes K, Sample HA, Wilson MR, Naccache SN, Arevalo S, Somasekar S, Federman S, Stryke D, Vespa P, Schiller G, Messenger S, Humphries R, Miller S, Klausner JD. Diagnosis of Fatal Human Case of St. Louis Encephalitis Virus Infection by Metagenomic Sequencing, California, 2016. Emerg Infect Dis. 2017 Oct;23(10):1964-1968. doi: 10.3201/eid2310.161986.

Reference Type RESULT
PMID: 28930022 (View on PubMed)

Murkey JA, Chew KW, Carlson M, Shannon CL, Sirohi D, Sample HA, Wilson MR, Vespa P, Humphries RM, Miller S, Klausner JD, Chiu CY. Hepatitis E Virus-Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing. Open Forum Infect Dis. 2017 Jun 13;4(3):ofx121. doi: 10.1093/ofid/ofx121. eCollection 2017 Summer.

Reference Type RESULT
PMID: 28721353 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://chiulab.ucsf.edu

brief description of PDAID study and referral link

http://www.ciapm.org/project/precision-diagnosis-acute-infectious-diseases

summary of the PDAID project, sponsored by the California Initiative to Advance Precision Medicine

https://www.youtube.com/watch?v=OFYSEowGfeI

video describing metagenomic next-generation sequencing and its use for diagnosis of infections

http://nextgendiagnostics.ucsf.edu

The UCSF Center for Next-Gen Precision Diagnostics

Other Identifiers

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P0509948

Identifier Type: -

Identifier Source: org_study_id

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