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

Study Description

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.

Condition or disease
Lyme Disease; Pediatric Infectious Disease; Erythema Migrans; Lyme Arthritis; Lyme Carditis; Lyme Disease Meningitis

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Next Generation Sequencing to Detect Borrelia Burgdorferi DNA in the Blood of Pediatric Patients With Lyme Disease
• Actual Study Start Date: July 24, 2018
• Estimated Primary Completion Date: May 31, 2020
• Estimated Study Completion Date: May 31, 2020

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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.

Biospecimen Retention:   Samples With DNA

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

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• 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

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

Contacts and Locations

Contacts

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

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

Locations

United States, New York

Clinical Research Center; Recruiting

Setauket, New York, United States, 11733-9219

Contact: Wendy Mattias 631-444-6900 wendy.mattias@stonybrookmedicine.edu

Contact: Erin Infanzon 631-444-8832 erin.infanzon@stonybrookmedicine.edu

Principal Investigator: Christy A Beneri

Sub-Investigator: Andrew Handel

Sponsors and Collaborators

Stony Brook University

Karius, Inc.

More Information

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.

• Responsible Party: Christy Beneri, Assistant Professor of Pediatrics, Stony Brook University
• ClinicalTrials.gov Identifier: NCT03505879
• Other Study ID Numbers: 1205731-1
• First Posted: April 23, 2018
• Last Update Posted: October 16, 2019
• Last Verified: October 2019

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

Keywords provided by Christy Beneri, Stony Brook University:

Next Generation Sequencing

Additional relevant MeSH terms:

Communicable Diseases; Infection; Lyme Disease; Erythema Chronicum Migrans; Glossitis, Benign Migratory; Meningitis; Erythema; Central Nervous System Diseases; Nervous System Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Skin Diseases; Skin Manifestations; Borrelia Infections; Tick-Borne Diseases; Spirochaetales Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Glossitis; Tongue Diseases; Mouth Diseases; Stomatognathic Diseases