Ignite Creation Date:
2024-05-06 @ 4:36 PM
Last Modification Date:
2024-10-26 @ 2:13 PM
Study NCT ID:
NCT05036707
Status:
RECRUITING
Last Update Posted:
2024-06-07
First Post:
2021-09-04
Brief Title:
Human Immune Response to Ixodes Scapularis Tick Bites
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Investigating the Human Immune Response to Ixodes Scapularis Tick Bites
Status:
RECRUITING
Status Verified Date:
2024-10-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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
1 Develop a model of acquired tick resistance in humans
2 Continue to assess the safety of tick feeding using laboratory-reared Ixodes scapularis larva in humans
Exploratory Objectives
1 Comparison of the early and late immune response in the skin site of the bite of Ixodes scapularis after a single tick exposure
2 Determine the effects of repeated tick feeding on the immune response at the tick bite site in human skin and development of tick resistance
3 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
4 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
1 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
2 Monitor safety adverse events AEs using reporting tools and Sponsor safety monitors
Exploratory Endpoints
1 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
2 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
3 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
4 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
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
1 Develop a model of acquired tick resistance in humans
2 Continue to assess the safety of tick feeding using laboratory-reared Ixodes scapularis larva in humans
Exploratory Objectives
1 Comparison of the early and late immune response in the skin site of the bite of Ixodes scapularis after a single tick exposure
2 Determine the effects of repeated tick feeding on the immune response at the tick bite site in human skin and development of tick resistance
3 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
4 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
1 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
2 Monitor safety adverse events AEs using reporting tools and Sponsor safety monitors
Exploratory Endpoints
1 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
2 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
3 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
4 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
True
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 000331-I | None | None | None |