Lyme DiseaseNCT02446626
Xenodiagnosis After Antibiotic Treatment for Lyme Disease
A study testing Skin biopsy, Blood draw and Xenodiagnosis in people with Lyme Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lyme Disease
- What is being tested?
- Skin biopsy, Blood draw and Xenodiagnosis
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 5 sitesUnited States
- Study dates
- 24 Jul 2015to 4 May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- LYME ARTHRITIS (N=40)
- Age 18 or older.
- Lyme arthritis and have not received antibiotic therapy for the disease.
- HEALTHY VOLUNTEERS (N=20)
- Age 18 or older.
- No prior history of Lyme disease.
- Negative whole cell enzyme-linked immunosorbent assay (ELISA) or C6-based antibody test for Lyme disease.
- Patients with recently diagnosed (acute) EM (within 48 hours of starting antibiotic therapy) and patients with untreated Lyme arthritis will be recruited in an attempt to increase the chances of finding a positive result by xenodiagnosis (an attempt of a positive control) While patients with acute untreated EM would be the best positive control group, it would be unethical to withhold therapy in these patients for the few days required for tick feeding, due to the risk of dissemination of the organism and possible morbidity. Patients with untreated Lyme arthritis will be recruited to establish whether xenodiagnosis can be used to identify infection in late stage Lyme patients where the bacterium is known to be present. These patients have been infected for months and will not be harmed for delaying therapy for a few days. Lyme arthritis is a late manifestation of B. burgdorferi infection, and hematogenous dissemination already occurred at this late stage. Studies have shown that the presence or absence of previous antibiotic treatment is more predictive than the duration of untreated arthritis for the success of antibiotic therapy in Lyme arthritis. Similarly, patients who just started therapy for EM may still have live Borrelia in the skin and xenodiagnosis may be able to recover the bacteria (but culture of skin biopsies from patients with EM become negative very quickly - within one dose - on antibiotic therapy).
- While treatment for Lyme disease will not be offered under this protocol, it may be available via different clinical research protocols or regular medical care at the study site. If not, treatment will be prescribed by the patient's primary care. For patients with untreated early Lyme disease (erythema migrans), antibiotics can be started at the same day of tick placement. For patients with untreated Lyme arthritis, antibiotics can be started after collection of xenodiagnostic ticks (usually 4-5 days, up to 7 days). For patients with Lyme arthritis, if less than 14 ticks fed successfully and if the participant agrees, antibiotic treatment can be delayed until after the repeat procedure.
- Patients with acute EM and untreated Lyme arthritis will be able to re-enroll as Patients with Lyme disease, post-therapy. Therefore, in case of positive results, we will be able to compare between the procedures.
- Negative control patients will include healthy volunteers from Lyme endemic areas who have never been diagnosed with Lyme disease and have a negative B. burgdorferi ELISA and C6 antibody titer.
Who cannot join
- No antibiotic therapy active against Lyme disease in the previous 3 months (except patients with acute EM). Prophylaxis with a single dose of doxycycline 200 mg is not an exclusion.
- 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.
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- 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.
- Oral or IV steroids in the previous 2 weeks (topical, nasal, inhaled, intra-articular, and replacement doses of steroids are not exclusions).
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Tufts Medical Center
Boston, Massachusetts, 02111
Stony Brook University (State University of New York)
Stony Brook, New York, 11794-8153
Mansfield Family Practice
Storrs, Connecticut, 06268
New York Medical College
Valhalla, New York, 10595
About this study
Official title: Xenodiagnosis After Antibiotic Treatment for Lyme Disease - Phase II Study
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.
Read more
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.
Read the detailed description
Lyme disease is the most common vector borne disease in the United States. Although antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for most patients early in the course of disease, a significant number of patients who receive therapy report persistent symptoms. The cause of persistent symptoms after antibiotic therapy for Lyme disease is an area of great controversy. Recent studies have shown that the organism (Borrelia burgdorferi) may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding (xenodiagnosis). Whether this occurs in humans is unknown. Currently available tests for human Lyme disease do not allow determination of persistent infection after antibiotic therapy.
We performed the first study of the use of I. scapularis larva for the xenodiagnosis of B. burgdorferi infection in humans. Our pilot study showed that xenodiagnosis was well tolerated with no severe adverse events (AEs). The most common AE was mild itching at the site. In this small pilot study, xenodiagnosis for B. burgdorferi was positive in 2 participants and indeterminate in 2 participants. Further studies are needed to determine the sensitivity of xenodiagnosis in evaluating the infection status of Lyme disease patients.
In this proposal, we want to further investigate the utility of xenodiagnosis for identifying persistence of infection with B. burgdorferi in treated human Lyme disease. Our objectives include assessing the link between detection of B. burgdorferi by xenodiagnosis and persistence of symptoms in patients diagnosed with Lyme disease, within 1 year, post therapy; compare the rate of detection of B. burgdorferi by xenodiagnosis after therapy in participants with posttreatment Lyme disease symptoms; identify subject characteristics related to the likelihood of detecting B. burgdorferi by xenodiagnosis including: time from infection, time between infection and therapy, time from therapy; and continue to assess the safety of xenodiagnosis in humans.
The results of study have the potential to resolve this long-standing controversy in Lyme disease pathogenesis. While xenodiagnosis is unlikely to be widely used in clinical practice due to the labor intensity and speed of testing, if our study shows a linkage between positive xenodiagnostic testing and persistence of symptoms after B. burgdorferi infection, it may prove to be a useful tool for testing new strategies for treatment and for correlation with more generally applicable diagnostic markers. Understanding the pathogenesis of persistent symptoms following Lyme disease, and identifying reliable diagnostic tests for determining the success of antibiotic therapy, is critical to the medical management of these patients.
- Conditions
- Lyme Disease
- Being tested
- Skin biopsy, Blood draw, Xenodiagnosis
- Keywords
- Lyme Disease, Ixodes scapularis, Borrelia Burgdorferi, Post treatment, Tick bite
- Medical subject headings
- Lyme Disease, Tick Bites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin biopsyProcedure or surgery
Optional 2-3mm skin punch biopsies will be performed.
Blood drawProcedure or surgery
Peripheral blood draws will be performed.
XenodiagnosisDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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) Receives: 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) Receives: 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) Receives: Procedure: Skin biopsy; Procedure: Blood draw; Device: Xenodiagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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
- Test ticks using isothermal amplification reaction included in the PCR electrospray ionization mass spectroscopy
- Test ticks by PCR using the Tick-borne disease Capture Sequencing Assay (TBDCapSeq)
Measured: 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.
Measured: Up to 30-days after tick removal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study start24 Jul 2015
- Primary completion4 May 2022
- Study completion4 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Lyme DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Stony Brook University, Mansfield Family Practice LLC, Tufts Medical Center, New York Medical College
- Responsible party
- Sponsor
- Investigators
- Adriana R Marques, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02446626
- Sponsor's protocol ID
- 150131
- Other IDs
- 15-I-0131
- Status last verified
- 5 May 2022
- First submitted
- 13 May 2015
- Last updated
- 3 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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.
PubMed 24523212Telford 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.
PubMed 25301228Hodzic 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.
PubMed 24466286Turk 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.
PubMed 31710647Marques 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.
PubMed 41563326
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Xenodiagnosis After Antibiotic Treatment for Lyme Disease - Phase II Study
- ClinicalTrials.gov ID
- NCT02446626
- Acronym / sponsor ID
- 150131
- Conditions
- Lyme Disease
- Keywords
- Lyme Disease, Ixodes scapularis, Borrelia Burgdorferi, Post treatment, Tick bite
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Stony Brook University, Mansfield Family Practice LLC, Tufts Medical Center, New York Medical College
- Study start
- 24 Jul 2015 (actual)
- Primary completion
- 4 May 2022 (actual)
- Study completion
- 4 May 2022 (actual)
- First posted
- 18 May 2015 (estimated)
- Results
- Posted 3 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Lyme disease is the most common vector borne disease in the United States. Although antibiotic therapy is clinically effective in treating the symptoms of Lyme disease for most patients early in the course of disease, a significant number of patients who receive therapy report persistent symptoms. The cause of persistent symptoms after antibiotic therapy for Lyme disease is an area of great controversy. Recent studies have shown that the organism (Borrelia burgdorferi) may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding (xenodiagnosis). Whether this occurs in humans is unknown. Currently available tests for human Lyme disease do not allow determination of persistent infection after antibiotic therapy.
We performed the first study of the use of I. scapularis larva for the xenodiagnosis of B. burgdorferi infection in humans. Our pilot study showed that xenodiagnosis was well tolerated with no severe adverse events (AEs). The most common AE was mild itching at the site. In this small pilot study, xenodiagnosis for B. burgdorferi was positive in 2 participants and indeterminate in 2 participants. Further studies are needed to determine the sensitivity of xenodiagnosis in evaluating the infection status of Lyme disease patients.
In this proposal, we want to further investigate the utility of xenodiagnosis for identifying persistence of infection with B. burgdorferi in treated human Lyme disease. Our objectives include assessing the link between detection of B. burgdorferi by xenodiagnosis and persistence of symptoms in patients diagnosed with Lyme disease, within 1 year, post therapy; compare the rate of detection of B. burgdorferi by xenodiagnosis after therapy in participants with posttreatment Lyme disease symptoms; identify subject characteristics related to the likelihood of detecting B. burgdorferi by xenodiagnosis including: time from infection, time between infection and therapy, time from therapy; and continue to assess the safety of xenodiagnosis in humans.
The results of study have the potential to resolve this long-standing controversy in Lyme disease pathogenesis. While xenodiagnosis is unlikely to be widely used in clinical practice due to the labor intensity and speed of testing, if our study shows a linkage between positive xenodiagnostic testing and persistence of symptoms after B. burgdorferi infection, it may prove to be a useful tool for testing new strategies for treatment and for correlation with more generally applicable diagnostic markers. Understanding the pathogenesis of persistent symptoms following Lyme disease, and identifying reliable diagnostic tests for determining the success of antibiotic therapy, is critical to the medical management of these patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort #1: Patients with Lyme disease, post-therapy | Active comparator | Procedure: Skin biopsy, Procedure: Blood draw, Device: XenodiagnosisParticipants 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. |
| Cohort #2: Patients with post-Lyme disease symptoms (PTLDs) | Active comparator | Procedure: Skin biopsy, Procedure: Blood draw, Device: XenodiagnosisParticipants 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. |
| Cohort #3: New Acute Erythema Migrans | Active comparator | Procedure: Skin biopsy, Procedure: Blood draw, Device: XenodiagnosisParticipant 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) |
| Cohort #4: Untreated Lyme Arthritis | Active comparator | Procedure: Skin biopsy, Procedure: Blood draw, Device: XenodiagnosisParticipant 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) |
| Cohort #5: Healthy Volunteers | Active comparator | Procedure: Skin biopsy, Procedure: Blood draw, Device: XenodiagnosisHealthy 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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.
Key exclusion criteria (15 listed)
- No antibiotic therapy active against Lyme disease in the previous 3 months (except patients with acute EM). Prophylaxis with a single dose of doxycycline 200 mg is not an exclusion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Skin biopsyOptional 2-3mm skin punch biopsies will be performed. | Procedure or surgery | 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 drawPeripheral blood draws will be performed. | Procedure or surgery | 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 |
| XenodiagnosisLarval 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. | Device | 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 |
Primary outcome
Detection of Borrelia Burgdorferi in Ticks After Xenodiagnosis Procedure
Time frame: 3-6 days post tick placement
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)
Participants With Adverse Event Related to the Application of Ticks (Xenodiagnosis)
Time frame: Up to 30-days after tick removal
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24523212Marques 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.
- Background: PubMed 25301228Telford 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.
- Background: PubMed 24466286Hodzic 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.
- Results publication: PubMed 31710647Turk 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.
- Derived from this study: PubMed 41563326Marques 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana R Marques, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Skin biopsy, Blood draw and Xenodiagnosis in people with Lyme Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection of Borrelia Burgdorferi in Ticks After Xenodiagnosis Procedure (time frame: 3-6 days post tick placement). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02446626, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2024.