Searching for Persistence of Infection in Lyme Disease

NCT01143558 | Completed Early Phase 1 FDA Device

• 2 other identifiers: 10013910-I-0139
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

Background: Lyme disease is an infection caused by Borrelia burgdorferi, a bacteria that is transmitted to humans by ticks. It can cause many different symptoms including rash, fever, headache, meningitis (infection of the central nervous system), and arthritis. While most patients improve after taking antibiotics, some patients continue to have symptoms. It is currently unknown why some patients continue to have symptoms. One possibility is that the antibiotics have not successfully gotten rid of all of the bacteria. Current tests for Lyme disease cannot tell whether the bacteria have been successfully eliminated from the body. Xenodiagnosis is a way to look for Borrelia bacteria using the animal that usually hosts them, Ixodes scapularis (also known as the deer tick). This method takes advantage of the evolution of the bacteria and the insect that transmits the infection, which can make the insect particularly good at finding the agent. In studies of animals, xenodiagnosis may be more sensitive than current tests for detecting the presence of the Lyme disease bacteria. Researchers are interested in using xenodiagnosis to determine whether uninfected ticks that feed on humans who have been infected with Lyme disease bacteria can detect the continued presence of live bacteria. Objectives: \- To determine whether xenodiagnosis can be used to successfully investigate the presence of Lyme disease bacteria. Eligibility:

• Participants will have an initial visit for a physical examination, medical history, and blood sample.
• For the first study visit, researchers will place a strip of filter paper or a small plastic container with 20 to 30 disease-free ticks on the participant s skin. If possible, the ticks will be placed at the site of a Lyme disease rash or another suspicious area, or on the nondominant forearm. Participants will be asked to keep the ticks in place, and will keep a diary card at home to record any symptoms or problems.
• The ticks will be collected 4 to 6 days after placement. At that visit, participants will have a skin biopsy taken of the area tested, a blood sample will be collected, and participants will receive a new diary card to keep until the next clinic visit.
• After 1 month, participants will provide a final blood sample, and will receive a follow-up phone call 2 months afterward.

Conditions

Lyme Disease

Keywords

Borrelia Burgdorferi; Xenodiagnosis; Ticks; Skin Biopsy; Lyme Disease

Outcome Measures

Primary Outcomes (5)

• To assess the safety of the planned xenodiagnostic procedure in humans. All individuals who underwent xenodiagnosis under the study will be assessed for adverse events

  AE reporting per protocol toxicity table

  full duration of the study

• To perform xenodiagnosis on subjects who have the characteristic EM rash and have been treated with antibiotics early in the course of Lyme disease.

  PCR and culture of samples

  Samples collected during tick removal visit.

• To perform xenodiagnosis on subjects who have a high C6 ELISA titer after antibiotic therapy.

  PCR and culture of samples

  Samples collected during tick removal visit.

• To perform xenodiagnosis on subjects with post Lyme disease syndrome.

  PCR and culture of samples

  Samples collected during tick removal visit.

• To perform xenodiagnosis on subjects with newly diagnosed EM lesions that are within 48 hrs of starting antibiotics.

  PCR and culture of samples

  Samples collected during tick removal visit.

Study Arms (1)

1

EXPERIMENTAL

All cohorts undergo the same intervention with the study device.

Device: Lyme Disease Xenodiagnosis

Interventions

Lyme Disease Xenodiagnosis DEVICE

Clean laboratory-bred ticks are the FDA registered IDE. These ticks are placed on patients to search for evidence of Borrelia burgdorferi.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Criteria for the diagnosis of Lyme disease can be found at The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America (4).
• Patients With EM (N=35), Post Treatment
• Age 18 or older
• EM diagnosed by the study physician or, with a diagnosis of EM that is thought to be highly likely by the study physician.
• Treatment with at least 1 course of antibiotics that fulfills the Infectious Diseases Society of America guidelines for the recommended therapy for Lyme disease. There must be at least 1 month and up to 4 months between the end of the therapy and the study procedures.
• High C6 Antibody Titer (N=35)
• Age 18 or older
• Diagnosed with confirmed or probable early or late Lyme disease as per Centers for Disease Control and Prevention (CDC) case definition (http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm), have received recommended antibiotic therapy and have a high C6 ELISA titer (index above 3) at least 6 months after therapy.
• Post Lyme disease syndrome (N=20)
• Age 18 or older
• Diagnosed with confirmed or probable early or late Lyme disease fulfilling the case definition of Lyme disease by the CDC (http://www.cdc.gov/ncphi/disss.nndss/caseded/lyme disease 2008.htm)
• Received recommended antibiotic therapy, with resolution or stabilization of the objective manifestation(s) of Lyme disease.
• New complaints of fatigue, paresthesias or dysesthesias, widespread musculoskeletal pain or cognitive difficulties within 6 months of the diagnosis of Lyme disease
• Symptoms are persistent or relapsing for at least a 6-month period after completion of antibiotic therapy, causing reduction in previous levels of occupational, educational, social, or personal activities.
• No antibiotic therapy active against Lyme disease in the previous 3 months.

You may not qualify if:

• History of allergy to surgical tape or Nitex nylon mesh
• History of severe reactions to tick bites (granuloma or systemic reactions)
• Inability to maintain the dressing for any reason
• Currently receiving any antibiotic or having received antibiotics in the last month (3 months for patients with post Lyme disease syndrome and high C6 titer) (except patients with EM on treatment)
• Pregnancy or lactation
• Unwillingness to use an effective method of birth control for 3 months after tick placement (women of child-bearing potential only)
• Not able to understand all of the requirements of the study or unable to give informed consent and/or comply with all aspects of the evaluation.
• Investigational therapy during the time of the study and/or in the month prior to signing the informed consent.
• Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin cancers, autoimmune disease requiring immunosuppressive therapy, or history of HIV, chronic viral hepatitis, or syphilis.
• Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study.
• History of forming large thick scars after skin injuries or surgery
• History of excessive bleeding after cuts or procedures
• Currently taking anticoagulants
• History of allergy to lidocaine
• Biopsies will not be done on face, neck, scalp, or over the tibia

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Yale University

New Haven, Connecticut, 06510-8005, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Tufts University

Boston, Massachusetts, 01536, United States

Location

Related Publications (3)

• Bockenstedt LK, Mao J, Hodzic E, Barthold SW, Fish D. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis. 2002 Nov 15;186(10):1430-7. doi: 10.1086/345284. Epub 2002 Oct 23.

  PMID: 12404158 BACKGROUND

• Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008 May;52(5):1728-36. doi: 10.1128/AAC.01050-07. Epub 2008 Mar 3.

  PMID: 18316520 BACKGROUND

• Marques A, Telford SR 3rd, Turk SP, Chung E, Williams C, Dardick K, Krause PJ, Brandeburg C, Crowder CD, Carolan HE, Eshoo MW, Shaw PA, Hu LT. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clin Infect Dis. 2014 Apr;58(7):937-45. doi: 10.1093/cid/cit939. Epub 2014 Feb 11.

  PMID: 24523212 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lyme Disease

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases

Study Officials

• Adriana R Marques, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 14, 2010
• Study Start: November 4, 2010
• Primary Completion: December 30, 2014
• Study Completion: December 30, 2014
• Last Updated: April 14, 2026

Record last verified: 2026-02-06

Locations

US (3)