Next Generation Sequencing Detection of Lyme Disease

• ClinicalTrials.gov Identifier: NCT03505879
• Recruitment Status: Recruiting
• First Posted: April 23, 2018
• Last Update Posted: October 16, 2019
• Sponsor: Stony Brook University
• Collaborator: Karius, Inc.
• Information provided by (Responsible Party): Christy Beneri, Stony Brook University

Tracking Information

• First Submitted Date: April 13, 2018
• First Posted Date: April 23, 2018
• Last Update Posted Date: October 16, 2019
• Actual Study Start Date: July 24, 2018
• Estimated Primary Completion Date: May 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2019)

• Ability of Next Generation Sequencing to detect Borrelia burgdorferi DNA in blood [ Time Frame: 1 year ]
  To determine if Next Generation Sequencing (NGS) is able to detect Borrelia burgdorferi DNA in the blood of pediatric patients with Lyme disease, including those with erythema migrans (single or multiple), Lyme meningitis, Lyme carditis, Lyme disease facial palsy, and Lyme arthritis
• NGS detection of Borrelia burgdorferi DNA following antibiotics [ Time Frame: 1 year ]
  To determine if Next Generation Sequencing (NGS) is able to detect Borrelia burgdorferi DNA in the blood of pediatric patients with a multiple erythema migrans rash shortly after the first dose of antibiotics.

Original Primary Outcome Measures (submitted: April 13, 2018)

• Ability of Next Generation Sequencing to detect Borrelia burgdorferi DNA in blood [ Time Frame: 5 months ]
  To determine if Next Generation Sequencing (NGS) is able to detect Borrelia burgdorferi DNA in the blood of pediatric patients with clinically-diagnosed erythema migrans (EM).
• NGS detection of Borrelia burgdorferi DNA in blood compared to serology [ Time Frame: 5 months ]
  To compare the ability to detect Borrelia burgdorferi infection among pediatric patients with an erythema migrans using NGS versus serology

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: April 13, 2018)

Changes in NGS detection of Borrelia burgdorferi DNA in blood over time [ Time Frame: 5 months ]

To determine if the detection of Borrelia burgdorferi DNA in pediatric patients with an EM changes over time after appropriate antibiotic treatment of Lyme disease.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Next Generation Sequencing Detection of Lyme Disease
• Official Title: Next Generation Sequencing to Detect Borrelia Burgdorferi DNA in the Blood of Pediatric Patients With Lyme Disease
• Brief Summary: Next Generation Sequencing is capable of sequencing millions of small strands of DNA from a single blood sample, potentially improving its sensitivity compared to PCR testing, which only detects predetermined larger strands of DNA. We will test the ability of NGS to detect Borrelia burgdorferi DNA in the blood of pediatric patients with Lyme disease. We will conduct an observational study of NGS testing on pediatric patients at all stages of Lyme disease. Study involvement will require a single study visit for clinical data collection and blood draw. We will enroll patients at all phases of suspected Lyme disease, collect clinically relevant information, and test for Lyme disease using Next Generation Sequencing and standard Lyme serologic testing. If the patient has multiple erythema migrans, Lyme meningitis, facial nerve palsy, arthritis, or carditis, a B. burgdorferi serum PCR will also be sent. Enrollment and Next Generation Sequencing blood draw will occur before or up to 24 hours after the first dose of antibiotics is administered. We will also study the impact of antibiotics on NGS testing by running the test 6-24 hours after antibiotics are started among a small subset of patients with a multiple erythema migrans rash. Collected data will be analyzed with basic descriptive statistics.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Whole blood samples for detection of infectious pathogens by next generation sequencing

• Sampling Method: Non-Probability Sample
• Study Population: Cases will include pediatric patients age 1 to <18 years old who currently have a specific Lyme disease syndrome and have been on antibiotics for less than 24 hours prior to blood draw

Condition

• Lyme Disease
• Pediatric Infectious Disease
• Erythema Migrans
• Lyme Arthritis
• Lyme Carditis
• Lyme Disease Meningitis

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• Schwartz AM, Hinckley AF, Mead PS, Hook SA, Kugeler KJ. Surveillance for Lyme Disease - United States, 2008-2015. MMWR Surveill Summ. 2017 Nov 10;66(22):1-12. doi: 10.15585/mmwr.ss6622a1.
• Theel ES. The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease. J Clin Microbiol. 2016 May;54(5):1191-6. doi: 10.1128/JCM.03394-15. Epub 2016 Feb 10. Review.
• Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005 Jul;18(3):484-509. Review.
• Babady NE, Sloan LM, Vetter EA, Patel R, Binnicker MJ. Percent positive rate of Lyme real-time polymerase chain reaction in blood, cerebrospinal fluid, synovial fluid, and tissue. Diagn Microbiol Infect Dis. 2008 Dec;62(4):464-6. doi: 10.1016/j.diagmicrobio.2008.08.016. Epub 2008 Oct 22.
• Kalish RA, McHugh G, Granquist J, Shea B, Ruthazer R, Steere AC. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease. Clin Infect Dis. 2001 Sep 15;33(6):780-5. Epub 2001 Aug 10.
• da Fonseca AJ, Galvão RS, Miranda AE, Ferreira LC, Chen Z. Comparison of three human papillomavirus DNA detection methods: Next generation sequencing, multiplex-PCR and nested-PCR followed by Sanger based sequencing. J Med Virol. 2016 May;88(5):888-94. doi: 10.1002/jmv.24413. Epub 2015 Nov 6.
• Abril MK, Barnett AS, Wegermann K, Fountain E, Strand A, Heyman BM, Blough BA, Swaminathan AC, Sharma-Kuinkel B, Ruffin F, Alexander BD, McCall CM, Costa SF, Arcasoy MO, Hong DK, Blauwkamp TA, Kertesz M, Fowler VG Jr, Kraft BD. Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation Sequencing. Open Forum Infect Dis. 2016 Jul 12;3(3):ofw144. eCollection 2016 Sep.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 13, 2018): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2020
• Estimated Primary Completion Date: May 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Lyme disease subjects (Cases):

Inclusion criteria:

1. Age 1 to <18 years old
2. The subject has spent time in a Lyme-endemic area during the previous month
3. The subject has a suspected Lyme disease infection

Exclusion criteria:

1. Past infection with Lyme disease
2. Received oral or IV antibiotics within 1 month prior to presentation Note: Subjects may be enrolled if NGS blood test can be drawn <24 hours after the first dose of Lyme diseasetargeted antibiotics is administered

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 17 Years (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Christy Beneri, DO; (631) 444-7692; Christy.Beneri@stonybrookmedicine.edu

Contact: Andrew Handel, MD; (631) 444-7692; Andrew.handel@stonybrookmedicine.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03505879
• Other Study ID Numbers: 1205731-1
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Christy Beneri, Stony Brook University
• Study Sponsor: Stony Brook University
• Collaborators: Karius, Inc.
• Investigators: Not Provided
• PRS Account: Stony Brook University
• Verification Date: October 2019