Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort

NCT02910037 | Completed Results FDA Device

• 1 other identifier: P0509948
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Encephalitis; Meningitis

Keywords

metagenomic next-generation sequencing; microbiological diagnosis; bacterial infections; viral infections; fungal infections; parasitic infections

Outcome Measures

Primary Outcomes (1)

• Total Number of Cases With at Least One Provider Response

  Investigators will evaluate impact of mNGS assay by clinician surveys and Clinical Microbial Sequencing Board (CMSB) feedback and discussion as measured by at least 1 provider response per case.

  within 1 month of patient enrollment in study

Secondary Outcomes (4)

• Clinical Outcomes: Time From Cerebrospinal Fluid Collection to mNGS Results

  from admission to 1 month post discharge for each patient during the enrollment period of study

• Clinical Outcomes: Length of Stay

  from admission to 1 month post discharge for each patient during the enrollment period of study

• Clinical Outcomes: Final Diagnosis Category

  from admission to time of final case review (1 month post discharge or up to one year)

• Clinical Outcomes: Concordance of mNGS With Other Molecular Testing on Cerebrospinal Fluid Pathogens

  from admission to 1 month post discharge for each patient during the enrollment period of study

Study Arms (1)

patients enrolled for mNGS testing

EXPERIMENTAL

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).

Device: mNGS for pathogen detection

Interventions

mNGS for pathogen detection DEVICE

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

Also known as: Sequence-Based Ultrarapid Pathogen Identification (SURPI)+, UCSF metagenomic next-generation sequencing testing

patients enrolled for mNGS testing

Eligibility Criteria

• Age: 1 Minute - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Demographic Criteria
• Age: any (no age limit)
• 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
• 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
• No known diagnosis of non-infectious etiology responsible for symptoms
• Time of enrollment: within 7 days of onset of symptoms, either initial presentation or acute exacerbation of presumed infectious syndrome.
• Specimen Criteria
• 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
• 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)
• No more than 3 freeze-thaw cycles

Sponsors & Collaborators

• University of California, San Francisco: lead
• California Initiative to Advance Precision Medicine: collaborator
• Sandler Foundation: collaborator
• Bowes Foundation: collaborator
• Charles and Helen Schwab Foundation: collaborator
• University of California, Davis: collaborator
• University of California, Los Angeles: collaborator
• Children's Hospital Los Angeles: collaborator
• Children's Hospital Colorado: collaborator
• St. Jude Children's Research Hospital: collaborator
• Children's National Research Institute: collaborator
• University of California, Berkeley: collaborator
• DNAnexus, Inc.: collaborator
• Syapse, Inc.: collaborator

Study Sites (7)

University of California, Davis Medical Center

Davis, California, 95616, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, Los Angeles Medical Center

Los Angeles, California, 90095, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94116, United States

Location

Children's Hospital Colordao

Denver, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

St. Jude Children's Research Hospital

Nashville, Tennessee, 37212, United States

Location

Related Publications (9)

• 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.

  PMID: 24896819 BACKGROUND

• 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.

  PMID: 26620704 BACKGROUND

• 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.

  PMID: 25572898 BACKGROUND

• 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.

  PMID: 25837569 BACKGROUND

• 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.

  PMID: 24899342 BACKGROUND

• 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.

  PMID: 26290222 BACKGROUND

• 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.

  PMID: 31189036 RESULT

• 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.

  PMID: 28930022 RESULT

• 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.

  PMID: 28721353 RESULT

Related Links

• brief description of PDAID study and referral link
• summary of the PDAID project, sponsored by the California Initiative to Advance Precision Medicine
• video describing metagenomic next-generation sequencing and its use for diagnosis of infections
• The UCSF Center for Next-Gen Precision Diagnostics

MeSH Terms

Conditions

Encephalitis; Meningitis; Bacterial Infections; Virus Diseases; Mycoses; Parasitic Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Charles Chiu
• Organization: The University of California, San Francisco

charles.chiu@ucsf.edu

(415) 514-8219

Study Officials

• Charles Y Chiu, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Hannah Sample, BS

  University of California, San Francisco

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 21, 2016
• Study Start: June 1, 2016
• Primary Completion: July 31, 2017
• Study Completion: July 31, 2017
• Last Updated: May 27, 2021
• Results First Posted: May 27, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: The clinical study report will be submitted for publication by June 2018.

Locations

US (7)