Xenodiagnosis After Antibiotic Treatment for Lyme Disease

NCT02446626 | Completed Results DMC FDA Device

• 2 other identifiers: 15013115-I-0131
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 5

Brief Summary

Background: The most common tick-borne illness in the United States, Lyme disease is caused by Borrelia burgdorferi bacteria that are transmitted to people by Ixodes scapularis ticks. Most cases of Lyme disease are cured by antibiotics, but some patients continue to experience symptoms despite the absence of detectable Lyme bacteria. Xenodiagnosis uses a vector to detect the presence of a disease-causing microbe. Researchers will use live, laboratory-bred ticks to see if Lyme disease bacteria can be detected in people after completing antibiotic therapy and if that is more common in people who continue to experience symptoms such as fatigue and joint pain. Objectives: \- To see if ticks can be used to detect B. burgdorferi in people who have had Lyme disease and received antibiotic therapy and if it correlates with persistent symptoms. Eligibility:

• Adults at least 18 years old who have:
• Untreated erythema migrans (the Lyme disease rash); OR
• Untreated Lyme arthritis; OR
• Continuing symptoms after treatment for Lyme disease; OR
• Had Lyme disease and antibiotic treatment within the past 12 months.
• Healthy volunteers Design:
• Participants will be screened with medical history, physical exam, and blood tests.
• Visit 1:
• Blood and urine tests, health questionnaire.
• Up to 30 laboratory-bred, pathogen-free, larval ticks (each smaller than a poppy seed) will be placed under a dressing.
• Participants may have two small biopsies of skin .
• 4 6 days later, Visit 2:
• Dressing will be removed and ticks will be collected.
• Participants will answer symptom questions.
• If many ticks are still attached, participants will have to come back the next day. If not enough ticks feed successfully, the procedure may be repeated.
• Participants will keep a diary of symptoms for 30 days. Over 3 months, they will be return to the clinic 3 times to see how they feel and answer questionnaires. Test results will be discussed.

Conditions

Lyme Disease

Keywords

Lyme Disease; Ixodes scapularis; Borrelia Burgdorferi; Post treatment; Tick bite

Outcome Measures

Primary Outcomes (2)

• Detection of Borrelia Burgdorferi in Ticks After Xenodiagnosis Procedure

  Recovered ticks after feeding on research participants were tested for presence of B. burgdorferi using at least one of three procedures: 1. Test ticks by polymerase chain reaction (PCR) and culture - Injection of tick lysate into severe combined immunodeficiency (SCID) mice with subsequent PCR and culture testing 2. Test ticks using isothermal amplification reaction included in the PCR electrospray ionization mass spectroscopy 3. Test ticks by PCR using the Tick-borne disease Capture Sequencing Assay (TBDCapSeq)

  3-6 days post tick placement

• Participants With Adverse Event Related to the Application of Ticks (Xenodiagnosis)

  Safety of xenodiagnosis in humans was assessed by number of participants with adverse event related to the application of ticks. Adverse event was assessed using participants self-reported diary cards and clinical interview.

  Up to 30-days after tick removal

Study Arms (5)

Cohort #1: Patients with Lyme disease, post-therapy

ACTIVE COMPARATOR

Participants with Lyme disease, post-therapy had 25-30 clean laboratory-reared larval ticks applied as close as possible to the previous site of Lyme disease manifestation. Ticks were secured under a retention dressing and allowed to attach to the research participant. Ticks were removed 3 - 6 days after the placement.

Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis

Cohort #2: Patients with post-Lyme disease symptoms (PTLDs)

ACTIVE COMPARATOR

Participants with post-treatment Lyme disease symptoms (PTLDS) at least 12-months from initial treatment had 25-30 clean laboratory-reared larval ticks applied as close as possible to the previous site of Lyme disease manifestation. Ticks were secured under a retention dressing and allowed to attach to the research participant. Ticks were removed 3 - 6 days after the placement.

Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis

Cohort #3: New Acute Erythema Migrans

ACTIVE COMPARATOR

Participant with new onset of acute erythema migrans had 25-30 clean laboratory-reared larval ticks applied as close as possible to the site of Lyme disease manifestation. Ticks were secured under a retention dressing and allowed to attach to the research participant. Ticks were removed 3 - 6 days after the placement. Acute erythema migrans participant (possible positive control)

Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis

Cohort #4: Untreated Lyme Arthritis

ACTIVE COMPARATOR

Participant with untreated Lyme arthritis had 25-30 clean laboratory-reared larval ticks applied as close as possible to the site of Lyme disease manifestation. Ticks were secured under a retention dressing and allowed to attach to the research participant. Ticks were removed 3 - 6 days after the placement. Lyme Arthritis participant (possible positive control)

Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis

Cohort #5: Healthy Volunteers

ACTIVE COMPARATOR

Healthy volunteers with no history of Lyme disease had 25-30 clean laboratory-reared larval ticks applied to a body site that was comfortable for participant. Ticks were secured under a retention dressing and allowed to attach to the research participant. Ticks were removed 3 - 6 days after the placement. Healthy Volunteers (negative control)

Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis

Interventions

Skin biopsy PROCEDURE

Optional 2-3mm skin punch biopsies will be performed.

Cohort #1: Patients with Lyme disease, post-therapy; Cohort #2: Patients with post-Lyme disease symptoms (PTLDs); Cohort #3: New Acute Erythema Migrans; Cohort #4: Untreated Lyme Arthritis; Cohort #5: Healthy Volunteers

Blood draw PROCEDURE

Peripheral blood draws will be performed.

Cohort #1: Patients with Lyme disease, post-therapy; Cohort #2: Patients with post-Lyme disease symptoms (PTLDs); Cohort #3: New Acute Erythema Migrans; Cohort #4: Untreated Lyme Arthritis; Cohort #5: Healthy Volunteers

Xenodiagnosis DEVICE

Larval ticks will be obtained from Dr. Sam Telford from a laboratory maintained tick colony at Tufts Veterinary School. These ticks are hatched from eggs laid by ticks that have fed only on specific pathogen free laboratory animals that were purchased from established vendors. Between 25-30 larval ticks that have been aged and are known to be ready to attach will be placed on the study participant.

Cohort #1: Patients with Lyme disease, post-therapy; Cohort #2: Patients with post-Lyme disease symptoms (PTLDs); Cohort #3: New Acute Erythema Migrans; Cohort #4: Untreated Lyme Arthritis; Cohort #5: Healthy Volunteers

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 and therapy for 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.
• PATIENTS WITH LYME DISEASE, POST-THERAPY (N=100)
• Age 18 or older
• Lyme disease diagnosed in the previous 13 months, fulfilling the case definition of confirmed or probable Lyme disease by the US Centers for Disease Control and Prevention (CDC) (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/).
• Completion of 1 course of antibiotics at least 3 months and up to 12 months between the end of the therapy and the xenodiagnostic procedure.
• Antibiotic treatment fulfills the Infectious Diseases Society of America guidelines for the recommended therapy for Lyme disease
• PATIENTS WITH POST-LYME DISEASE COMPLAINTS AT LEAST 12 MONTHS FROM INITIAL TREATMENT (N=40)
• Age 18 or older.
• Diagnosed with confirmed or probable Lyme disease fulfilling the case definition of Lyme disease by the CDC (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/).
• Received recommended antibiotic therapy for Lyme disease 5 at least 12 months between the end of the initial antibiotic therapy and the xenodiagnostic procedure.
• Persistent or recurrent symptoms that began or worsened within 6 months of the diagnosis and treatment for Lyme disease.
• ACUTE EM (N=40)
• Age 18 or older.
• EM diagnosed by the study physician.
• Receiving antibiotic therapy for Lyme disease for less than 48 hours.

You may not qualify if:

• History of allergy to surgical tape or dressing.
• History of severe reactions to tick bites (granuloma or systemic reactions).
• Inability to maintain the dressing for any reason.
• Pregnancy or lactation.
• Unwillingness to use an effective method of birth control for the duration of participation in the study (women of child-bearing potential only) and for at least 3 months following the last tick placement.
• Use of investigational therapy and devices 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.
• Refusal to participate in specimen collection and storage for future study related use.
• History of forming large thick scars (keloids) after skin injuries or surgery.
• History of excessive bleeding after cuts or procedures.
• Currently taking anticoagulants.
• History of allergy to lidocaine.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Stony Brook University: collaborator
• Mansfield Family Practice LLC: collaborator
• Tufts Medical Center: collaborator
• New York Medical College: collaborator

Study Sites (5)

Mansfield Family Practice

Storrs, Connecticut, 06268, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Stony Brook University (State University of New York)

Stony Brook, New York, 11794-8153, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Related Publications (5)

• 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 BACKGROUND

• Telford SR 3rd, Hu LT, Marques A. Is there a place for xenodiagnosis in the clinic? Expert Rev Anti Infect Ther. 2014 Nov;12(11):1307-10. doi: 10.1586/14787210.2014.966084.

  PMID: 25301228 BACKGROUND

• Hodzic E, Imai D, Feng S, Barthold SW. Resurgence of persisting non-cultivable Borrelia burgdorferi following antibiotic treatment in mice. PLoS One. 2014 Jan 23;9(1):e86907. doi: 10.1371/journal.pone.0086907. eCollection 2014.

  PMID: 24466286 BACKGROUND

• Turk SP, Lumbard K, Liepshutz K, Williams C, Hu L, Dardick K, Wormser GP, Norville J, Scavarda C, McKenna D, Follmann D, Marques A. Post-treatment Lyme disease symptoms score: Developing a new tool for research. PLoS One. 2019 Nov 11;14(11):e0225012. doi: 10.1371/journal.pone.0225012. eCollection 2019.

  PMID: 31710647 RESULT

• Marques AR, Ng SP, McCarthy JE, Telford SR 3rd, Dardick K, Wormser GP, Marcos LA, Tokarz R, Williams C, Law M, Norville J, Lundt M, Petnicki-Ocwieja T, Scavarda C, McKenna D, Goethert HK, Mateja A, Follman D, Eshoo MW, Hu LT. Xenodiagnosis to search for Borrelia burgdorferi after antibiotic treatment of Lyme disease: a prospective cohort study. Clin Infect Dis. 2026 Jan 21:ciag031. doi: 10.1093/cid/ciag031. Online ahead of print.

  PMID: 41563326 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lyme Disease; Tick Bites

Interventions

Blood Specimen Collection; Xenodiagnosis

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Microbiological Techniques

Results Point of Contact

• Title: Marques, Adriana
• Organization: National Institute of Allergy and Infectious Diseases

amarques@niaid.nih.gov

+1 301 435 7668

Study Officials

• Adriana R Marques, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 18, 2015
• Study Start: July 24, 2015
• Primary Completion: May 4, 2022
• Study Completion: May 4, 2022
• Last Updated: June 3, 2024
• Results First Posted: June 3, 2024

Record last verified: 2022-05-05

Locations

US (5)