Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort (PDAID)

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

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

    • California
      • Davis, California, United States, 95616
        • University of California, Davis Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90095
        • University Of California, Los Angeles Medical Center
      • San Francisco, California, United States, 94116
        • University of California, San Francisco Medical Center
    • Colorado
      • Denver, Colorado, United States, 80045
        • Children's Hospital Colordao
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • St. Jude Children's Research Hospital

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

  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

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

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
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 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
Investigators will review medical records to determine time of initial presentation and measure the time to mNGS results.
from admission to 1 month post discharge for each patient during the enrollment period of study
Clinical Outcomes: Length of Stay
Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study
Investigators will review medical records to determine length of stay including discharge to rehab facilities.
from admission to 1 month post discharge for each patient during the enrollment period of study
Clinical Outcomes: Final Diagnosis Category
Time Frame: from admission to time of final case review (1 month post discharge or up to one year)
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.
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
Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study
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).
from admission to 1 month post discharge for each patient during the enrollment period of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

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

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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