Lyme Test Indication Combinations (LyTIC) Study (LyTIC)

To establish performance of individual tests and combinations of tests (serological, molecular and cellular tests) in early Lyme infection diagnosis

Study Overview

• Status: Terminated
• Conditions: Lyme Disease
• Intervention / Treatment: Diagnostic test: PCR based assay; Diagnostic test: Serology based assay; Diagnostic test: Tcell based assay

Detailed Description

The present study aims to investigate the performance characteristics of both established and new assays for Borrelia burgdorferi infection and to assess the relative performance of appropriate combinations of these tests. The study will also investigate the effect of the time course of the infection and its treatment on the outcomes for the various tests. Polymerase Chain Reaction(PCR), serology and T cell based tests will be performed. In addition, tests for Babesia, Anaplasma, Ehrlichia and Rickettsia will also be performed as these pathogens can be carried by the same tick that carries Borrelia and may result in coinfection.

• Study Type: Observational
• Enrollment (Actual): 410

Contacts and Locations

Study Locations

• United States
  • California
    • Redding, California, United States, 96001
      • Paradigm Clinical Research
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research
    • Norwalk, Connecticut, United States, 06850
      • Circle Care Center
    • Stamford, Connecticut, United States, 06905
      • Orthopaedic Foundation for Active Lifestyles, Inc
  • Delaware
    • Georgetown, Delaware, United States, 19958
      • Delaware Integrated Medicine
  • Florida
    • Hialeah, Florida, United States, 33013
      • Eastern Research, Inc.
    • Hialeah, Florida, United States, 33016
      • South Florida Clinical Trials SFCT, A member of the Alliance, Inc.
    • Miami, Florida, United States, 33136
      • South Coast Research Center
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advance Clinical Research
  • Maine
    • Bangor, Maine, United States, 04401
      • Acadia Clinical Research
    • Portland, Maine, United States, 01430
      • Integrative Health Center of Maine
  • Maryland
    • Eldridge, Maryland, United States, 21075
      • Centennial Medical Group
    • Hagerstown, Maryland, United States, 21740
      • Klein & Associates, MD, PA
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research, Inc.
    • Rockville, Maryland, United States, 20854
      • Rockville Internal Medicine Group
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • NECCR Primacare Research,LLC
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
    • New Bedford, Massachusetts, United States, 02740
      • Metromedic Walk In
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
    • Westford, Massachusetts, United States, 02790
      • NECCR Primacare Research, LLC
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Asthma and Allergy Institute of MI
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research
  • Minnesota
    • Sartell, Minnesota, United States, 56377
      • Pinnacle Research
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Andrea Gaito
    • Florham Park, New Jersey, United States, 07932
      • MAffiliated Medical Associates
  • New York
    • Brooklyn, New York, United States, 11207
      • Modern Medical
    • Brooklyn, New York, United States, 11219
      • Private Practice-Johnathan Liebowitz
    • Brooklyn, New York, United States, 12298
      • NY Arthritis Clinic
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • Flushing, New York, United States, 11367
      • Private Practice-David Wurwitz
    • Glens Falls, New York, United States, 12801
      • Adirondack Medical Research Center
    • New York, New York, United States, 10022
      • NYCT, A member of Alliance, Inc.
    • Newburgh, New York, United States, 12550
      • Mid Hudson Medical Research
    • Port Jefferson, New York, United States, 11777
      • John T. Mather Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research
    • Columbus, Ohio, United States, 43207
      • Buckeye Health and Research
    • Toledo, Ohio, United States, 43207
      • Toledo Institute of Clinical Research
  • Pennsylvania
    • Barto, Pennsylvania, United States, 19504
      • Bally Medical Group
    • Boyertown, Pennsylvania, United States, 18512
      • Boyertown Medical Assoc.
    • Collegeville, Pennsylvania, United States, 19426
      • Collegeville Family Practice
    • Downingtown, Pennsylvania, United States, 19335
      • Brandywine Clinic
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • East Norriton, Pennsylvania, United States, 19401
      • Pediatric Medical Associates of NTN/ABG
    • Erie, Pennsylvania, United States, 16506
      • Liberty Family Practice/Square 1
    • Lansdale, Pennsylvania, United States, 19446
      • Detweiler Family Practice
    • Lansdale, Pennsylvania, United States, 19446
      • Green and Seidner Family Practice
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Assoc.
    • Pottstown, Pennsylvania, United States, 19465
      • Brookside Family Practice and Pediatrics
    • Royersford, Pennsylvania, United States, 19468
      • Spring-Ford Family Practice
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Safe Harbor Clinical Research
    • Lincoln, Rhode Island, United States, 02865
      • Ocean State Clinical Research
    • Portsmouth, Rhode Island, United States, 02871
      • NECCR Primacare Research, LLC
  • Texas
    • Lytle, Texas, United States, 78052
      • Atascosa Clinical Trial
  • Vermont
    • Hinesburg, Vermont, United States, 05461
      • Brookside Family Health Care
  • Virginia
    • Arlington, Virginia, United States, 22207
      • Millennium Clincial Trials
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine
    • Lynchburg, Virginia, United States, 24501
      • The Education and Research Foundation, Inc.
    • Manassas, Virginia, United States, 21010
      • Manassas Clinical Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Exemplar Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

500 subjects aged 5 years or older.

Description

Inclusion Criteria:

• Cohort 1a (typical EM and intention to treat):

Inclusion

1. Documented new onset Lyme disease EM rash (single or multiple) with photographic evidence provided to Oxford Immunotec.
2. Patient must be able to provide blood sample at the initial visit (prior to treatment initiation) and subsequent samples according to the schedule.
3. Patients 5 years of age or older, with a minimum weight of 40 pounds.
4. Patient able to read English and to give consent to study participation.
5. If patient is younger than 18 years of age a legally authorized representative must provide consent.

Cohort 1b (no typical EM; Lyme disease symptoms; intention to treat):

Inclusion

1. Patients with suspected Lyme disease, based on physician's examination, where the physician has the intention to treat for Lyme disease (i.e. patients who following initial examination were prescribed treatment for Lyme disease).
2. Documented new onset of Lyme disease symptoms without a typical EM rash or with no rash. If a rash is present, photographic evidence must be provided.
3. Patient must be able to provide blood sample at the initial visit (prior to treatment initiation) and subsequent samples according to the schedule.
4. Patients 5 years of age or older, with a minimum weight of 40 pounds.
5. Patient able to read English and to give consent to study participation.
6. If patient is younger than 18 years of age a legally authorized representative must provide consent.

Cohort 2 (Healthy subjects):

Inclusion

1. Subjects 5 years of age or older, with a minimum weight of 40 pounds.
2. Subjects never diagnosed with any tick borne disease including Lyme disease
3. Subjects able to read English and to give consent to study participation.
4. If subject is younger than 18 years of age a legally authorized representative must provide consent.

Exclusion Criteria:

• Exclusion Cohort 1a (typical EM and intention to treat):

  1. Patients with Lyme-like symptoms lasting longer than 1 month prior to study enrolment.
  2. Patients receiving treatment for any tick borne disease (including Lyme disease) prior to enrolment.
  3. Patients who received a Lyme vaccination.
  4. Patients with anemia defined as a serum hemoglobin <10gm/dL.
  5. Patients who are participating in, or plan to participate in, any investigational drug study.
  6. Patients who are considered unsuitable for the study by the Investigator.

Cohort 1b (no typical EM; Lyme disease symptoms; intention to treat):

1. Patients with Lyme-like symptoms lasting longer than 1 month prior to study enrolment.
2. Patients receiving treatment for any tick borne disease (including Lyme disease) prior to enrolment.
3. Patients who received a Lyme vaccination.
4. Patients with anemia defined as a serum hemoglobin <10gm/dL.
5. Patients who are participating in, or plan to participate in, any investigational drug study.
6. Patients who are considered unsuitable for the study by the Investigator.

Cohort 2 (Healthy subjects):

Exclusion

1. Subjects with a history of tick bite
2. Subjects with past or current tick borne disease diagnosis
3. Subjects at risk for tick borne diseases including Lyme disease
4. Subjects residing in endemic regions for tick borne diseases: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia and Wisconsin.
5. Subjects who have ever visited non-urban areas of endemic regions for tick borne diseases: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia and Wisconsin.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1a:Lyme patients- Erythema Migrans(EM)rash present; Patients with newly diagnosed Lyme disease based on the presence of a physician-documented EM rash. PCR, serology and Tcell based assay.	Diagnostic test: PCR based assay; Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined. In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).; Diagnostic test: Serology based assay; The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.; The Immunetics C6 Lyme ELISA assay.; A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines; A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections. Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.; Diagnostic test: Tcell based assay; A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.
1b:Lyme patients no typical EM; Patients documented symptoms of early Lyme disease, without a typical EM rash present, and the physician's intention to treat for Lyme disease. PCR, serology and Tcell based assay	Diagnostic test: PCR based assay; Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined. In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).; Diagnostic test: Serology based assay; The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.; The Immunetics C6 Lyme ELISA assay.; A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines; A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections. Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.; Diagnostic test: Tcell based assay; A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.
Cohort 2: healthy controls; Patients drawn from Lyme disease non-endemic areas and subjects with known exposure to Lyme disease will be excluded. PCR, serology and Tcell based assay.	Diagnostic test: PCR based assay; Whole blood specimens will be tested for the presence of Borrelia DNA by PCR in a two-step test (Imugen). In Cohort 1a and 1b. The first step tests for the presence of any Borrelia DNA. The second step is employed on positive samples and tests for the presence of either B. burgdorferi DNA or B. miyamotoi DNA. Positivity by PCR has a short but early window in the infection cycle for Borrelia burgdorferi and results may enable this window period and diagnosis rates to be better defined. In addition co-infection PCR analysis will be performed for the presence of Babesia, Anaplasma or Ehrlichia DNA (Imugen).; Diagnostic test: Serology based assay; The Imugen Lyme Antibody Analysis which includes immunoglobulin M (IgM),immunoglobulin G (IgG), and immunoglobulin A (IgA) antibody capture immunoassay and IgG and IgM based Western blots. In Cohort 1a and 1b.; The Immunetics C6 Lyme ELISA assay.; A 2-tier Lyme test performed and interpreted according to Centers for Disease Control (CDC) Guidelines; A Rickettsia antibody test will be used to identify Spotted Fever and Typhus fever groups infections. Lyme test methodologies generally indicate a need to run a combination of tests in order to overcome limitations in either sensitivity or specificity of the various individual tests. Performance of all these tests on the same set of samples should enable both individual and combinatorial performance values to be calculated and compared.; Diagnostic test: Tcell based assay; A research based ELISpot assay will be performed on peripheral blood mononuclear cells (PBMC) extracted from whole blood samples to test for presence of T cells activated against Borrelia antigens. Unlike serology based methods, this signal may not persist over extended periods of time in the absence of Borrelia antigens. The diagnostic window may be different for a test measuring adaptive immune response (i.e. T cells) and thus such test may identify patients with undetectable antibody response and may aid sensitivity of diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sample Data Analysis	The results will be used to calculate performance, including sensitivity and specificity of the tests under evaluation. The utility of these tests at different time points post initial presentation will be evaluated.	Tests at different time points post inital presentation will be evaluated through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Oxford Immunotec

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Tick-Borne Diseases; Borrelia Infections; Spirochaetales Infections; Lyme Disease
• Other Study ID Numbers: L3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No