CClinicalTrials.gg
RecruitingNCT07435649IMPACTUpdated Sep 14, 2026

Investigation of the Delve Detect Cerebrospinal Fluid (CSF) Metagenomic Next-generation Sequencing (mNGS) Test When Used for the Initial Diagnostic Workup of Patients With Suspected Central Nervous System (CNS) Infection

An interventional study of Delve Detect CSF mNGS Test and Real-World Data in Central Nervous System Infection, sponsored by Delve Bio, Inc.. Recruiting at 5 sites in United States. Per ClinicalTrials.gov, last updated 2026-09-14.

Sponsored by Delve Bio, Inc. · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
400
Allocation
Non-randomized
Sex
All
01

Study summary

Delve Bio, Inc. is a developer of novel mNGS tests with the goal of aiding in the diagnosis of infectious diseases in several clinical indications that may not have alternative traditional diagnostic methods routinely available. A proof of concept for the clinical utility of this mNGS testing methodology has been described in several seminal publications.1,2,3,4 Delve Bio is currently offering one of these assays as a laboratory-developed test (LDT) performed in a CLIA-certified, CAP-accredited laboratory. The test is called Delve Detect CSF. Delve Detect CSF is an mNGS in vitro diagnostic test intended for the simultaneous detection and differentiation of nucleic acids from multiple bacteria, viruses, fungi, and parasites in CSF from individuals suspected of meningitis or encephalitis. Delve Detect CSF identifies microbial nucleic acid in an unbiased and pathogen-agnostic manner.

Historically, due to its cost and turnaround times, which can be on the order of 14 days, CSF mNGS testing is typically employed as a "test of last resort" for patients with suspected infectious meningitis and encephalitis, and is often used when traditional diagnostic methods cannot identify the cause of infection. In the IMPACT Study, we seek to investigate the diagnostic and clinical utility of mNGS testing if it is employed earlier in the diagnostic workup of patients with suspected CNS infection and unknown etiology in conjunction with a more rapid turnaround time for test results on the order of two business days from sample receipt by the laboratory. Participants who meet the inclusion/exclusion criteria and undergo informed consent (and assent as applicable) will be enrolled in the study, assigned to the appropriate subpopulation category, and obtain CSF testing with Delve Detect CSF in addition to other SOC testing. In addition to the Delve Detect CSF test results, associated clinical information and health economic data for the participants will be obtained through chart abstraction. Clinical information will be de-identified wherever possible, and any PHI being collected will not be individually reported as part of the intended analysis. The site investigator or their designee at each site will complete a survey to provide a consensus view of the treatment team regarding how the availability of Delve Detect CSF test results in early diagnostic workup affected clinical decision-making.

Analyses of the test results from Delve Detect CSF and other SOC diagnostic methods, in addition to the clinical information, will not be used to identify any participant. Information generated through the study will be recorded in such a manner that the identity of the human participants cannot readily be ascertained directly or through identifiers linked to the participants, and the participants will not be contacted. The results from this study could be used to support publications in scientific white papers, manuscripts, posters, and/or presentations.

02

Conditions studied

  • Central Nervous System Infection

Keywords

  • Delve Bio
  • IMPACT Study
  • mNGS
  • Central Nervous System (CNS) Infection
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  1. Must be willing and able to provide informed consent or have a legally authorized representative (LAR) willing and able to provide informed consent for participation in the study:

    a. Adults, 18 years of age or older, must provide informed consent, or if unable to provide consent, must have voluntary informed consent provided by a LAR b. Children \< 18 years of age must have informed consent provided by a parent, guardian, or LAR, and: i. If 7 years of age or older, must provide voluntary assent for participation, unless unable to do so If less than 7 years of age, assent should also be obtained, if feasible.

  2. Individuals presenting with, or admitted or transferred with, suspected CNS infection with at least 2 of the following clinical signs and symptoms:

    1. Headache
    2. Photophobia
    3. Neck stiffness
    4. Nausea/vomiting
    5. Documented fever ≥ 38°C (100.4°F)
    6. Altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥ 24 h with no alternative cause identified
    7. Generalized or partial seizures not fully attributable to a preexisting seizure disorder, identified toxic-metabolic derangement, or alcohol withdrawal
    8. Abnormality of brain parenchyma on neuroimaging suggestive of CNS infection that is either new from prior studies or appears acute in onset
    9. Abnormal spinal cord imaging suggestive of myelitis

Note: The clinical signs and symptoms list above applies to non-infant participants (≥ 1 year old). Infants (\< 1 year old) who are suspected of CNS infection may be enrolled if they present with fever ≥ 38°C (100.4°F) OR hypothermia \< 36.5°C (97.7°F) AND at least 1 of the following clinical signs and symptoms:

  1. Bulging fontanel (soft spot)
  2. Lethargy or irritability
  3. Refusing to feed or poor feeding
  4. Apnea
  5. Hypotonia or Hypertonia

Exclusionary participant characteristics:

  1. Unable to obtain consent (or assent, as applicable) from potential participant or legally authorized representative (LAR)
  2. Established diagnosis of non-infectious etiology responsible for symptoms of meningitis/encephalitis/myelitis, with confirmation prior to lumbar puncture (LP) being performed
  3. Established diagnosis of infectious etiology responsible for symptoms with microbiologic confirmation prior to LP being performed
  4. Established diagnosis of infectious etiology responsible for symptoms prior to CSF sample being sent for testing with Delve Detect CSF

    Note: participants already consented and enrolled in the study who obtain a positive test result from SOC testing prior to the CSF sample being sent for testing with Delve Detect CSF will be withdrawn from the study and excluded from analysis.

  5. Low clinical suspicion for infection with one of the following known diagnoses related to the patient admission prior to LP being performed. Remote history of these diagnoses does not exclude the patient from eligibility:

    1. Trauma
    2. Ischemic or hemorrhagic stroke unless suspected to be due to infectious etiology
    3. Postictal or metabolic encephalopathy
    4. Malignancy without present infection symptoms
    5. Demyelinating disease

    Exclusionary CSF sample characteristics:

  6. No evidence of CSF pleocytosis (defined as CSF white blood cell count (WBC) ≥ 5 cells per μL) in the first LP collected.

    Note: Exclusion criterion 4 applies to participants who are immunocompetent or otherwise not known to have a current immunodeficiency or immunocompromised status. Individuals with a current immunodeficiency or immunocompromised status (as defined in Section 9.3) may be enrolled with or without the presence of CSF pleocytosis and continue to final analysis.

  7. Insufficient residual CSF volume available for Delve Detect testing (\< 500 μL)
  8. The residual CSF sample available for testing with Delve Detect CSF was not the first diagnostic LP for the participant's current admission
  9. Residual CSF was stored at room temperature for ≥ 6 hours
  10. Residual CSF was stored refrigerated (2-8 °C) for ≥ 7 days
  11. Residual CSF was stored frozen (≤ -70 °C) for ≥ 90 days
  12. Residual CSF experienced more than a cumulative two freeze-thaw cycles
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
400 participants (estimated)

Study arms

  • Experimental
    Prospectively Collected Patients tested with Delve Detect mNGS

    Participants will be identified as candidates for the prospective enrollment population by clinicians who are treating the patients and/or laboratory investigators performing clinical testing on initial samples obtained from the patients through inpatient or ICU admission. Patients may be identified and enrolled in the study prior to or after CSF collection has been performed. Following informed consent and assent procedures, as applicable, participants will be enrolled in the study. Following enrollment and informed consent/assent, 500 - 1000 µL of CSF specimen collected as part of the first LP for SOC diagnostic workup will be sent for mNGS testing with the Delve Detect CSF test. Delve Detect CSF test results will be provided to treating physicians for clinical decision-making.

    Diagnostic Test: Delve Detect CSF mNGS Test

  • Active comparator
    Real-World Data Control Cohort

    RWD will be used to construct a control dataset for patients who were diagnosed and treated without the use of CSF mNGS. An attempt will be made to match the calendar time period/duration, and proportions of sex, age, disease, etiology (infectious/non-infectious), and subpopulation categories as the prospective enrollment population. The intent of the control population is to enable secondary and exploratory outcome comparisons by collecting data for patients who were diagnosed and treated without the use of CSF mNGS testing.

    Other: Real-World Data

Interventions

  • Diagnostic testDelve Detect CSF mNGS Test

    This cohort consists of patients admitted with suspected CNS infection, who will receive Delve Detect CSF mNGS testing from a prospectively collected CSF specimen. The results of the Delve Detect CSF mNGS Test will be returned to the patient's treatment team for clinical decision making.

  • OtherReal-World Data

    For the analysis of secondary and exploratory outcomes, a control population of patients who were diagnosed and treated without the use of CSF mNGS testing will be constructed using real-world data (RWD). The control population will have approximately equal proportions of demographics, disease severity, and subpopulation categories as the prospective enrollment population. RWD will be used to examine the potential effect that testing with Delve Detect CSF had on the selected outcomes with the prospectively enrolled participants by collecting data for patients who were diagnosed and treated without the use of CSF mNGS testing. These participants will be enrolled in the non-mNGS control population and have de-identified RWD collected through a waiver of informed consent as appropriate for comparison to the prospective enrollment population.

05

What researchers measure

Primary outcomes

  1. Overall Diagnostic Yield

    The primary endpoint of the study is to investigate the utility of Delve Detect CSF with respect to the overall diagnostic yield compared to SOC diagnostic testing.

    Time frame: From Enrollment to 90 Days Post-Discharge for Each Patient

06

Study locations

4 of 5 sites recruiting
  • University of California at San Francisco at Zuckerberg San Francisco General
    San Francisco, California 94110, United States
    • Colette Match, PhD, MPH · Contact · colette.match@ucsf.edu · 628-206-3595
    • Colette Match, PhD, MPH · Principal investigator
    Recruiting
  • Emory University Hospital
    Atlanta, Georgia 30322, United States
    • Anna Piantadosi, MD, PhD · Contact · anne.piantadosi@emory.edu · 404-712-9005
    • Anne Piantadosi, MD, PhD · Principal investigator
    • Rami Waked, MD · Sub investigator
    • Colleen Kraft, MD · Sub investigator
    Recruiting
  • University of Maryland, Baltimore
    Baltimore, Maryland 21201, United States
    • Jonathan Baghdadi, MD, PhD · Contact · jbaghdadi@som.umaryland.edu · 410-706-0066
    • Jonathan Baghdadi, MD, PhD · Principal investigator
    Not yet recruiting
  • Lahey Hospital & Medical Center
    Burlington, Massachusetts 01805, United States
    Recruiting
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
    • Buddy Creech, MD, MPH · Contact · buddy.creech@vumc.edu · 615-343-0332
    • Buddy Creech, MD, MPH · Principal investigator
    • Stephanie Rolsma, MD, PhD · Sub investigator
    • Susan G Johnson, MSN · Sub investigator
    Recruiting
07

References and documents

Publications

  • Benoit P, Brazer N, de Lorenzi-Tognon M, Kelly E, Servellita V, Oseguera M, Nguyen J, Tang J, Omura C, Streithorst J, Hillberg M, Ingebrigtsen D, Zorn K, Wilson MR, Blicharz T, Wong AP, O'Donovan B, Murray B, Miller S, Chiu CY. Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections. Nat Med. 2024 Dec;30(12):3522-3533. doi: 10.1038/s41591-024-03275-1. Epub 2024 Nov 12. PubMed 39533109 ↗
  • 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. PubMed 31189036 ↗
  • Miller S, Naccache SN, Samayoa E, Messacar K, Arevalo S, Federman S, Stryke D, Pham E, Fung B, Bolosky WJ, Ingebrigtsen D, Lorizio W, Paff SM, Leake JA, Pesano R, DeBiasi R, Dominguez S, Chiu CY. Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid. Genome Res. 2019 May;29(5):831-842. doi: 10.1101/gr.238170.118. Epub 2019 Apr 16. PubMed 30992304 ↗
  • 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. PubMed 24896819 ↗

Individual participant data

Plan to share: Undecided — Analyses of the test results from the Delve Detect CSF mNGS Test and any other SOC diagnostic methods, in addition to the clinical information, will not be used to identify any participant. Following informed consent, participants will be de-identified through the assignment of a unique number according to a standard procedure that will be provided to each investigational site. The participant ID will be used in conjunction with the unique Delve Detect CSF ID number included on each CSF specimen transfer tube used for mNGS testing for each participant. The results from this study could be used to support publications in scientific white papers, manuscripts, posters, and/or presentations.

08

Registry details

Key details

Study ID
NCT07435649
Lead sponsor
Delve Bio, Inc.
Responsible party
Sponsor
First posted
Feb 27, 2026
Start date
May 1, 2026
Primary completion
Jun 1, 2027 (estimated)
Completion
Sep 1, 2027 (estimated)
Last update
Sep 14, 2026

Study contacts

Steve Miller, M.D., Ph.D.
Contact
steve.miller@delve.bio
844-221-7423
Timothy Blicharz, Ph.D.
Contact
tim.blicharz@delve.bio
Steve Miller, M.D., Ph.D.
principal investigator · Delve Bio, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion