Human Immune Response to Ixodes Scapularis Tick Bites

NCT05036707 | Recruiting Phase 1 FDA Device

• 2 other identifiers: 10000331000331-I
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tick Resistance; Lyme Disease; Tick-borne Diseases

Keywords

Tick Immunity; Tick-borne diseases; Vaccines; Lyme Disease

Outcome Measures

Primary Outcomes (2)

• Assessment of Safety of the device. Use toxicity tables and safety monitoring as specified in the protocol.

  Ongoing assessment of safety.

  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.

  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...

  continuous

• Exploratory: Analyze gene expression of Ixodes scapularis after feeding on humans using RNASeq.

  continuous

• Exploratory: Compare early and late immune response in skin after Ixodes scapularis bite. Use RNASeq, histology, immunohistochemistry, digital spatial profiling to explore.

  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.

  continous

Study Arms (1)

1

ACTIVE COMPARATOR

Healthy Volunteer

Device: Xenodiagnosis Ticks; Procedure: skin biopsy; Procedure: blood draw

Interventions

Xenodiagnosis Ticks 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.

1

skin biopsy PROCEDURE

2-3 mm skin punch biopsies will be performed.

1

blood draw PROCEDURE

Peripheral blood draws will be performed.

1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Serum IgE level within Clinical Center Department of Laboratory Medicine normal range.
• https://ccinternal2.cc.nih.gov/LTGRA/UL/public\_labtest\_detail.aspx?next\_flg=Y\&test\_id=4731\&id\_order=53
• Serum tryptase level within Clinical Center Department of Laboratory Medicine normal range.
• https://ccinternal2.cc.nih.gov/LTGRA/UL/public\_labtest\_detail.aspx?next\_flg=Y\&test\_id=1157\&id\_order=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

You may not qualify if:

• 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.
• Inability to maintain the dressing for any reason.
• Pregnancy or lactation.
• Treatment with another investigational drug or other intervention within the past 30 days.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• 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

• Ribeiro 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.

  PMID: 16431279 BACKGROUND

• Valenzuela JG. Exploring tick saliva: from biochemistry to 'sialomes' and functional genomics. Parasitology. 2004;129 Suppl:S83-94. doi: 10.1017/s0031182004005189.

  PMID: 15938506 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Tick-Borne Diseases; Lyme Disease

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Adriana R Marques, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siu-Ping Ng, R.N.

CONTACT

(301) 451-7661; sturk1@mail.nih.gov

Adriana R Marques, M.D.

CONTACT

(301) 435-7244; amarques@niaid.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2021
• First Posted: September 8, 2021
• Study Start: February 28, 2022
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05-04

Locations

US (1)