- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02910037
Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort (PDAID)
May 7, 2021 updated by: University of California, San Francisco
Clinical Implementation of Metagenomic Next-Generation Sequencing for Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
214
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Davis, California, United States, 95616
- University of California, Davis Medical Center
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Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, United States, 90095
- University Of California, Los Angeles Medical Center
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San Francisco, California, United States, 94116
- University of California, San Francisco Medical Center
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Colorado
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Denver, Colorado, United States, 80045
- Children's Hospital Colordao
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Tennessee
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Nashville, Tennessee, United States, 37212
- St. Jude Children's Research Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 minute to 110 years (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Exclusions:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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).
|
This assay is a laboratory-validated metagenomic test for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Number of Cases With at Least One Provider Response
Time Frame: within 1 month of patient enrollment in study
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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.
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within 1 month of patient enrollment in study
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Outcomes: Time From Cerebrospinal Fluid Collection to mNGS Results
Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study
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Investigators will review medical records to determine time of initial presentation and measure the time to mNGS results.
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from admission to 1 month post discharge for each patient during the enrollment period of study
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Clinical Outcomes: Length of Stay
Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study
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Investigators will review medical records to determine length of stay including discharge to rehab facilities.
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from admission to 1 month post discharge for each patient during the enrollment period of study
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Clinical Outcomes: Final Diagnosis Category
Time Frame: from admission to time of final case review (1 month post discharge or up to one year)
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Investigators will review medical records to determine final diagnosis after all diagnostic testing has been performed including metagenomic Next-Gen sequencing and autopsy where applicable.
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from admission to time of final case review (1 month post discharge or up to one year)
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Clinical Outcomes: Concordance of mNGS With Other Molecular Testing on Cerebrospinal Fluid Pathogens
Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study
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mNGS findings were compared to conventional testing for concordance.
Conventional testing included both tests that were ordered as part of each patients workup and those order to confirm mNGS findings on cerebrospinal fluid (CSF).
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from admission to 1 month post discharge for each patient during the enrollment period of study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Charles Y Chiu, MD, PhD, University of California, San Francisco
- Study Director: Hannah Sample, BS, University of California, San Francisco
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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. Erratum In: Genome Med. 2016;8(1):1. Klenschmidt-DeMasters, Bette K [corrected to Kleinschmidt-DeMasters, Bette K].
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2016
Primary Completion (Actual)
July 31, 2017
Study Completion (Actual)
July 31, 2017
Study Registration Dates
First Submitted
September 13, 2016
First Submitted That Met QC Criteria
September 19, 2016
First Posted (Estimate)
September 21, 2016
Study Record Updates
Last Update Posted (Actual)
May 27, 2021
Last Update Submitted That Met QC Criteria
May 7, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- P0509948
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
All genomic / metagenomic sequencing data from this study will be made available either at NIH Sequence Read Archive or NIH database of Genotypes and Phenotypes (dbGaP), depending on whether human sequence data is included.
The investigators intend to make de-identified ancillary clinical, laboratory, and radiographic data available as well upon request.
IPD Sharing Time Frame
The clinical study report will be submitted for publication by June 2018.
IPD Sharing Supporting Information Type
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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