Tick-borne DiseasesPhase 1/2NCT05036707
Human Immune Response to Ixodes Scapularis Tick Bites
A Phase 1/2 study testing Xenodiagnosis Ticks, skin biopsy and blood draw in people with Tick-borne Diseases and Tick Resistance, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Each year, the number of cases of tick-borne diseases increases. The deer tick (Ixodes scapularis) is the vector of at least 7 pathogens that cause human diseases, including Lyme disease. Researchers want to learn more to help them develop vaccines against ticks in the future. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Tick-borne Diseases, Tick Resistance, Lyme Disease
- What is being tested?
- Xenodiagnosis Ticks, skin biopsy and blood draw
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2022to 30 Jun 2029
- Phase
- Phase 1/2
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 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Age 18 years or older.
- In good general health as evidenced by medical history.
- No history of TBD.
- No known tick bite.
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- Serum IgE level within Clinical Center Department of Laboratory Medicine normal range.
- https://ccinternal2.cc.nih.gov/LTGRA/UL/publiclabtestdetail.aspx?nextflg=Y\&testid=4731\&idorder=53
- Serum tryptase level within Clinical Center Department of Laboratory Medicine normal range.
- https://ccinternal2.cc.nih.gov/LTGRA/UL/publiclabtestdetail.aspx?nextflg=Y\&testid=1157\&idorder=1
- For participants of child-bearing potential: use of effective contraception for at least 1 month prior to tick placement, and agreement to use such a method during study participation and for an additional 3 months after the removal of the last ticks. Types of contraception include abstinence, surgical methods (sterilization, implants, intrauterine device, partner with vasectomy), hormonal methods (birth control pill, patch, ring, injection), or barrier methods (diaphragm plus spermicide, male condom plus spermicide)
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
- Agree to not participate in other clinical studies requiring investigational interventions for the duration of the study.
- Minimum hemoglobin of 13.0 g/dL for males and 12 g/dL for females
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- History of forming large thick scars (keloids) after skin injuries.
- History of excessive bleeding after cuts or procedures.
- History of taking anticoagulants in the past 28 days.
- History of allergic reaction to lidocaine.
- History of allergic reaction to tape, adhesive bandages, or dressings.
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- Inability to maintain the dressing for any reason.
- Pregnancy or lactation.
- Treatment with another investigational drug or other intervention within the past 30 days.
- Oral or intravenous (IV) steroids in the 2 weeks prior to each tick placement procedure (topical, nasal, inhaled, intra-articular, and replacement doses of steroids are not exclusions).
- History of reactions to mammalian meat, IgE- mediated food allergies, urticaria or anaphylaxis. Mild pollen-food allergy syndrome is not an exclusion.
- History of systemic allergic reaction to venom (bee, wasps and other Hymenoptera stings).
- History of clinically significant drug allergies.
- History of moderate to severe atopy asthma, atopic dermatitis, allergic rhinitis.
- Active severe skin disease, uncontrolled diabetes, cancer other than non-melanoma skin cancers, autoimmune disease requiring immunosuppressive therapy, or history of human immunodeficiency virus (HIV), chronic viral hepatitis, or syphilis.
- Refusal to allow storage of samples and data for future usage.
- 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.
- Children:
- Children are excluded from this protocol as there is no direct benefit to the participants, the risk from the skin biopsies is small but above minimal, the procedure is invasive and can be stressful for children, and there is concern over their ability to maintain the LeFlap dressing.
- Pregnant and breastfeeding women:
- Pregnant and breastfeeding women are excluded from trial participation as there is no direct benefit to the participants.
- Adults who lack or lose decision-making capacity to consent to research participation:
- Adults lacking decision-making capacity to provide informed consent are excluded at screening as there is no direct benefit to the participants. Enrolled participants who permanently or temporarily lose the ability to consent after receiving the first tick exposure procedure will be advised to continue study visits for safety monitoring but will have no additional research procedures performed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: Investigating the Human Immune Response to Ixodes Scapularis Tick Bites
Background:
Each year, the number of cases of tick-borne diseases increases. The deer tick (Ixodes scapularis) is the vector of at least 7 pathogens that cause human diseases, including Lyme disease. Researchers want to learn more to help them develop vaccines against ticks in the future.
Read more
Objective:
To learn how people s bodies, particularly the skin, respond to tick bites.
Eligibility:
Healthy adults aged 18 years and older who have no known history of a tick-borne disease or tick bite exposure.
Design:
Participants will be screened with a medical history, physical exam, and blood tests.
Participants will have 2 skin punch biopsies of healthy skin. For this, a sharp instrument will be used to remove a round plug of skin about the size of a pencil eraser. Participants will then have 10 clean laboratory-bred ticks placed at 2 different sites on their skin (20 ticks total). The ticks will be removed from the first site 1 day after placement and from the second site 2-4 days after placement. Participants will complete symptom diary cards. They will answer questions about itching at the tick feeding sites. They will give blood samples. Photos will be taken of the tick feeding sites. Skin punch biopsies will be collected at the sites of the tick bites.
Participants will repeat the tick feeding procedures 2 times, each 2-8 weeks apart. For the 2nd and 3rd procedures, 10 clean laboratory-bred ticks will be placed at 1 site. The ticks will be removed 2-3 days after tick placement. They will have telephone follow-up visits after each procedure.
After the final tick removal, participants will have follow-up visits in 4-6 weeks and again in 3 months. They will give blood samples and discuss how they are feeling.
Participation will last about 5-7 months.
Read the detailed description
Study Description:
This study aims to develop a model for acquired tick resistance in humans, characterize the acquisition of tick-associated skin immunity, and monitor the innate and adaptive immune response of Ixodes scapularis tick bites. The study will be a prospective, non-randomized, single-center study performed at the National Institutes of Health (NIH) Clinical Center. It will be performed under Investigational Device Exemption (IDE) G210153 and will be monitored as per National Institute of Allergy and Infectious Diseases (NIAID) and NIH regulations. Participants (35 adult healthy volunteers) will undergo up to 3 tick feeding placements, 2 to 8 weeks
apart. One to two punch skin biopsies (2-3 mm) from the tick bite sites will be collected at 1 day (early) and 2-4 days (late) after the first tick placement procedure. Skin biopsies of an unaffected site will be performed as a control. One to two punch skin biopsies (2-3 mm) from the tick bite sites will be collected at day 2-3 after the 2nd and 3rd tick placement procedures. Additionally, blood will be collected to evaluate systemic immune response to tick salivary proteins. Ticks will also be collected at each timepoint and gene expression will be analyzed to determine the effect of the human skin response on ticks.
Changes in resistance to tick bites can be evaluated by:
- Local reaction to the tick bite
- pruritus
- site reactions
- Blood flow index as measured by laser speckle contrast imaging
- Number of fed ticks
Changes in the immune response and cellular recruitment in the skin can be evaluated using:
Differential expression of immune transcripts and other skin associated transcripts using RNAseq or other high-throughput profiling of cells.
Conventional histology and immunohistochemistry
Digital Spatial Profiling to determine cell type and other immune markers using a high-plex platform
Changes in the systemic immune response will be evaluated by:
Measurement of antibodies against tick salivary proteins will be assessed by enzyme-linked immunosorbent assay (ELISA) and
western blot
Novel state-of-the-art high-resolution technologies to deeply characterize the immune response to tick bites over time, both phenotypically and functionally.
Changes in tick transcriptomic profile will be assessed by:
RNAseq: Ribonucleic acid (RNA) will be isolated from tick after they have been removed from subjects and unexposed ticks.
Differential expression profile will be performed and validated by NanoString
Objectives:
Primary Objectives:
- Develop a model of acquired tick resistance in humans
- Continue to assess the safety of tick feeding using laboratory-reared Ixodes scapularis larva in humans
Exploratory Objectives:
- Comparison of the early and late immune response in the skin site of the bite of Ixodes scapularis after a single tick exposure.
- Determine the effects of repeated tick feeding on the immune response at the tick bite site in human skin and development of tick resistance.
- Analyze the evolution of the systemic immune response to tick bite in participants after multiple tick exposures and validate development of reliable biomarkers of tick exposure.
- Analyze gene expression of Ixodes scapularis larvae feeding on humans and determine the effects of immune response of subjects repeatedly bitten on larvae gene expression.
Endpoints:
Primary Endpoints:
- Pruritus at the site of tick attachment in the first 24 hours of tick placement over the three placements as measured by a positive slope over the three placements of the numerical rating score. The slope of other pruritus scores at 24 hours and at Day 2-4, and the number of attached ticks collected from participants over the three placements will also be measured.
- Monitor safety adverse events (AEs) using reporting tools and Sponsor safety monitors.
Exploratory Endpoints:
- Compare the results from the skin biopsies acquired with the first tick placement. Our hypothesis is that there will be differential phenotypic, transcriptomic, and immunohistochemical differences between:
- Exposed (bitten skin at day 1) and unexposed (unbitten skin)
- Exposed (bitten skin at day 2-4) and unexposed (unbitten skin)
- Exposed (bitten skin at day 1) and exposed (bitten skin at day 2-4) Measurement of changes will be assessed by:
- Differential expression of immune transcripts and other skin associated transcripts using RNAseq
- Conventional histology and immunohistochemistry
- Digital Spatial Profiling to determine cell type and other immune markers using a high-plex platform
- Compare the changes in the local immune response and cellular recruitment between the 1st, 2nd and the 3rd tick exposures and correlate with measures of itching, blood flow index and number of attached ticks and the feeding status. We postulate that differences between the timepoints will become more marked with multiple exposures. We hypothesize that there will be differential phenotypic and transcriptomic differences between: Exposed (bitten skin at day 2-3, exposure 2) and exposed (bitten skin at day 2-3, exposure 3) Correlate these changes with measures of resistance to tick feeding (itching, number and level of feeding of attached ticks, blood flow index).
- Compare the development of antibody responses against Ixodes scapularis salivary protein antigens between the 1st, 2nd, and the 3rd tick exposures and correlate antibodies against tick salivary proteins with measures of resistance (itching, erythema, blood flow index, number of fed ticks). Explore the development of the host response in blood using high resolution technologies such as immunophenotyping, proteomics and transcriptomics and compare the responses between the 1st, 2nd, and the 3rd tick exposures.
- Using RNAseq technology, measure changes in gene expression of ticks fed at early timepoint (1 day) vs late timepoint (2-4 days) vs unfed ticks and of ticks fed at 1st, 2nd, and 3rd placements. Correlation of pruritus and changes in tick gene expression.
- Conditions
- Tick-borne Diseases, Tick Resistance, Lyme Disease
- Being tested
- Xenodiagnosis Ticks, skin biopsy, blood draw
- Keywords
- Tick Immunity, Tick-borne diseases, Vaccines, Lyme Disease
- Medical subject headings
- Tick-Borne Diseases, Lyme Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xenodiagnosis TicksDevice
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.
skin biopsyProcedure or surgery
2-3 mm skin punch biopsies will be performed.
blood drawProcedure or surgery
Peripheral blood draws will be performed.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Healthy Volunteer Receives: Device: Xenodiagnosis Ticks; Procedure: skin biopsy; Procedure: blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol.
Ongoing assessment of safety.
Measured: continuous
Develop a model of acquired tick resistance in humans. Use validated pruritus scales, numerical rating system, verbal rating system, and visual analogue system.
Clinical measures of tick immunity.
Measured: end of study
Secondary outcomes (4)
Exploratory: Determine the effects of repeated tick feeding on immune response at tick bite site and the development of resistance. Use RNASeq,histology, immunohistochemistry, digital spatial profiling, clinical itch scales, site reactions, tick...
Compare changes in early and late local immune response and cellular recruitment between the 1st and 3rd tick exposures.
Measured: continuous
Exploratory: Analyze gene expression of Ixodes scapularis after feeding on humans using RNASeq.
Measure changes in gene expression of ticks fed at the various time points.
Measured: continuous
Exploratory: Compare early and late immune response in skin after Ixodes scapularis bite. Use RNASeq, histology, immunohistochemistry, digital spatial profiling to explore.
Compare early and late immune response in the skin using skin biopsies collected at Day 1 and Day 4.
Measured: continuous
Exploratory: Analyze the evolution of the systemic immune response to tick bite by measuring antibodies response (ELISA and western blot) against Ixodes scapularis salivary protein antigens.
Compare the development of antibody responses against Ixodes scapularis salivary antigens between the 1st, 2nd, and 3rd tick feedings.
Measured: continous
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2021
- Study start28 Feb 2022
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Tick-borne DiseasesStudies 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 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- 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
- NCT05036707
- Sponsor's protocol ID
- 10000331
- Other IDs
- 000331-I
- Status last verified
- 16 Sep 2026
- First submitted
- 4 Sep 2021
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: It is not yet known if the research results will reveal a need to disclose IPD, therefore it is undecided if we plan to make IPD available.
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 24523212Ribeiro JM, Alarcon-Chaidez F, Francischetti IM, Mans BJ, Mather TN, Valenzuela JG, Wikel SK. An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochem Mol Biol. 2006 Feb;36(2):111-29. doi: 10.1016/j.ibmb.2005.11.005. Epub 2005 Dec 20.
PubMed 16431279Valenzuela JG. Exploring tick saliva: from biochemistry to 'sialomes' and functional genomics. Parasitology. 2004;129 Suppl:S83-94. doi: 10.1017/s0031182004005189.
PubMed 15938506