Hyper-Immunoglobulin E. Syndrome (HEIS)Early Phase 1NCT03921515
Skin Immunity Sample Collection Involving Blisters and Biopsies
A Early Phase 1 study testing Blister induction and Skin Biopsies in people with Hyper-Immunoglobulin E. Syndrome (HEIS) and Chronic Granulomatous Disease (CGD), run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people. Read more about this study
- Who is it for?
- Ages 7 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyper-Immunoglobulin E. Syndrome (HEIS), Chronic Granulomatous Disease (CGD)
- What is being tested?
- Blister induction and Skin Biopsies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2024to 10 Dec 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 7 to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Meets one of the following:
- has documentation of HIES or CGD (patient populations); or
- does not have clinically apparent evidence of an immune defect or history of invasive or recurrent S. aureus infections (healthy volunteers).
- Between the following age limits (inclusive):
- 18 and 65 years old for healthy volunteers;
- 7 and 65 years old for patients with CGD;
Show all 9Show fewer
- 18 and 65 years old for patients with HIES.
- Willing to allow storage of blood, RNA, bacterial and fungal cultures, and other tissue samples for future research.
- Able to provide informed consent.
Who cannot join
- The following exclusion criteria apply to all subjects:
- For individuals undergoing blister or skin biopsy procedures, history of keloid formation.
- Current or prior (within 3 months) anticoagulant or anti-platelet therapy (other than aspirin or non-steroidal anti-inflammatory drugs [NSAIDs]).
- Current or prior (within 3 months) use of immunomodulatory drugs (e.g., chemotherapy, steroids), except if approved by the principal investigator.
- Pregnancy.
- Any condition that, in the opinion of the investigator, contraindicates participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people.
Read more
Objective:
To learn about how immune response and skin healing are related to each other.
Eligibility:
People ages 18-65 with hyper IgE syndrome or Job syndrome or people ages 7-65 with chronic granulomatous disease. Healthy volunteers ages 18 65 are also needed.
Design:
Participants will be screened with:
Medical history
Physical exam
Possible urine tests
Participants will have 1 to 3 visits within about a week. Visits will include the following:
Participants will have a wells device strapped to the inside of the forearm. It will suction the skin and pull the top layer away to form 8 blisters. The skin over the blisters and the liquid inside will be collected.
Participants will have up to 4 skin biopsies. A sharp tool will remove a small plug of skin from the forearm.
Participants may have blood and urine tests.
The skin on participants skin will be rubbed with a cotton swab.
Some participants will have an overnight visit. They will have the blister device placed back on the arm. The wells will be lined up over the blister wounds. The wells will be filled with either saline or the participant s blood serum. The device will be covered and left on the arm for up to 24 hours. Doctors will periodically remove some liquid from the wells.
Read the detailed description
The incidence of community-associated (CA) staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), has increased in recent years. Skin and soft tissues are the primary sites for these infections. Although many patients without apparent underlying immune dysfunction suffer from recurrent and persistent skin infections with S.aureus, patients with conditions such as hyper immunoglobulin E syndrome (HIES, or Job s syndrome) and chronic granulomatous disease (CGD) are disproportionately affected. Although underlying host molecular defects responsible for some of these predisposing conditions have been uncovered in recent years, the skin immune response to S. aureus infections has not been elucidated in either healthy volunteers or susceptible populations. We hypothesize that the local skin response determines susceptibility to S. aureus skin infection.
In this sample collection protocol, we will perform exploratory evaluations of anti-staphylococcal immune responses in healthy volunteers, subjects with HIES, and subjects with CGD. Following screening and baseline procedures, including blood draw and skin swab, subjects will have the option to undergo blister induction, where a suction device will be used to induce skin blisters on the forearm. The tops of the blisters and blister fluid will be collected for research testing and storage for future research. An optional overnight inpatient stay may be performed to collect additional cellular infiltrates in response to autologous serum and/or sterile saline. Subjects may also have up to 4 skin punch biopsies from the forearm over the course of a week to capture wound healing progress and identify involved genes. All research procedures will be performed at the National Institutes of Health Clinical Center (NIH CC).
The primary objective of this research is to perform ex vivo assessment of wound healing pathways using a skin blister model and skin biopsies to obtain keratinocyte cultures and evaluate skin immune responses. We will use three experimental approaches: 1) ex vivo evaluation of anti-microbial responses and tissue remodeling through derivation of keratinocyte cultures from skin blisters and biopsies, 2) in vivo and ex vivo assessment of cellular response after blister induction using overnight exposure to autologous serum and/or sterile saline, and 3) evaluation of in vivo responses to skin biopsies. We anticipate that the research will provide critical new information on the human skin immune and remodeling responses and will have direct relevance for the development of vaccines, diagnostics, and therapeutics.
- Being tested
- Blister induction, Skin Biopsies
- Keywords
- Hyper-Immunuglobulin E.Syndrome, Chronic Granulomatous Disease, Tumor Necrosis Factor Alpha, Staphylococcus Aureus
- Medical subject headings
- Granulomatous Disease, Chronic, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blister inductionOther
Blister induction involves creating 8 blisters on the forearm and removing the tops of the blisters for primary cell culture derivation. After blister induction, subjects may have an optional overnight admission to assess cell infiltration in response to autologous serum and/or sterile saline solution.
Skin BiopsiesOther
The skin biopsies will involve up to 4 biopsies: 2 initial punch biopsies 2 mm in diameter, followed by a punch biopsy 3 (plus or minus 1) and 7 (plus or minus 2) days later using a 3 mm punch to encompass the initial biopsy sites, capturing the tissue at 3 and 7 days of healing.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Blister Induction Receives: Other: Blister induction |
| 2 | Other | Skin Biopsies Receives: Other: Skin Biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor necrosis factor alpha (TNFa) production by keratinocytes from patients with HIES versus healthy volunteers
Evaluate epithelial cell responses to cutaneous wounds and infections of keratinocytes and other cutaneous epithelial cells in patients with HIES or CGD and healthy volunteers.
Measured: Throughout study
T-cell infiltration as percent of total cell infiltration in patients with CGD versus healthy volunteers.
Identify cellular mediators that contribute to the inflammatory processthrough evaluation of infiltrating cell types.
Measured: Throughout study
Fold induction in genes related to wound healing.
Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT).
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2019
- Study start9 Dec 2024
- Primary completion10 Dec 2024
- Study completion10 Dec 2024
Why it stopped: Study closed by PI, no enrollment.
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 Hyper-Immunoglobulin E. Syndrome (HEIS)Studies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ian A Myles, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03921515
- Sponsor's protocol ID
- 190084
- Other IDs
- 19-I-0084
- Status last verified
- Dec 2024
- First submitted
- 18 Apr 2019
- Last updated
- 13 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71. doi: 10.1001/jama.298.15.1763.
PubMed 17940231Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003 Dec 10;290(22):2976-84. doi: 10.1001/jama.290.22.2976.
PubMed 14665659Myles IA, Datta SK. Staphylococcus aureus: an introduction. Semin Immunopathol. 2012 Mar;34(2):181-4. doi: 10.1007/s00281-011-0301-9. Epub 2012 Jan 27. No abstract available.
PubMed 22282052
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Skin Immunity Sample Collection Involving Blisters and Biopsies
- ClinicalTrials.gov ID
- NCT03921515
- Acronym / sponsor ID
- 190084
- Keywords
- Hyper-Immunuglobulin E.Syndrome, Chronic Granulomatous Disease, Tumor Necrosis Factor Alpha, Staphylococcus Aureus
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study closed by PI, no enrollment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- 10 Dec 2024 (actual)
- Study completion
- 10 Dec 2024 (actual)
- First posted
- 19 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The way the body heals and protects itself from getting sick is called the immune response. Some people with weak immune systems get sick often or get rashes and skin infections. Researchers want to find out how the immune system and skin problems are related so they can help these people.
Objective:
To learn about how immune response and skin healing are related to each other.
Eligibility:
People ages 18-65 with hyper IgE syndrome or Job syndrome or people ages 7-65 with chronic granulomatous disease. Healthy volunteers ages 18 65 are also needed.
Design:
Participants will be screened with:
Medical history
Physical exam
Possible urine tests
Participants will have 1 to 3 visits within about a week. Visits will include the following:
Participants will have a wells device strapped to the inside of the forearm. It will suction the skin and pull the top layer away to form 8 blisters. The skin over the blisters and the liquid inside will be collected.
Participants will have up to 4 skin biopsies. A sharp tool will remove a small plug of skin from the forearm.
Participants may have blood and urine tests.
The skin on participants skin will be rubbed with a cotton swab.
Some participants will have an overnight visit. They will have the blister device placed back on the arm. The wells will be lined up over the blister wounds. The wells will be filled with either saline or the participant s blood serum. The device will be covered and left on the arm for up to 24 hours. Doctors will periodically remove some liquid from the wells.
Detailed description
The incidence of community-associated (CA) staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), has increased in recent years. Skin and soft tissues are the primary sites for these infections. Although many patients without apparent underlying immune dysfunction suffer from recurrent and persistent skin infections with S.aureus, patients with conditions such as hyper immunoglobulin E syndrome (HIES, or Job s syndrome) and chronic granulomatous disease (CGD) are disproportionately affected. Although underlying host molecular defects responsible for some of these predisposing conditions have been uncovered in recent years, the skin immune response to S. aureus infections has not been elucidated in either healthy volunteers or susceptible populations. We hypothesize that the local skin response determines susceptibility to S. aureus skin infection.
In this sample collection protocol, we will perform exploratory evaluations of anti-staphylococcal immune responses in healthy volunteers, subjects with HIES, and subjects with CGD. Following screening and baseline procedures, including blood draw and skin swab, subjects will have the option to undergo blister induction, where a suction device will be used to induce skin blisters on the forearm. The tops of the blisters and blister fluid will be collected for research testing and storage for future research. An optional overnight inpatient stay may be performed to collect additional cellular infiltrates in response to autologous serum and/or sterile saline. Subjects may also have up to 4 skin punch biopsies from the forearm over the course of a week to capture wound healing progress and identify involved genes. All research procedures will be performed at the National Institutes of Health Clinical Center (NIH CC).
The primary objective of this research is to perform ex vivo assessment of wound healing pathways using a skin blister model and skin biopsies to obtain keratinocyte cultures and evaluate skin immune responses. We will use three experimental approaches: 1) ex vivo evaluation of anti-microbial responses and tissue remodeling through derivation of keratinocyte cultures from skin blisters and biopsies, 2) in vivo and ex vivo assessment of cellular response after blister induction using overnight exposure to autologous serum and/or sterile saline, and 3) evaluation of in vivo responses to skin biopsies. We anticipate that the research will provide critical new information on the human skin immune and remodeling responses and will have direct relevance for the development of vaccines, diagnostics, and therapeutics.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Other: Blister inductionBlister Induction |
| 2 | Other | Other: Skin BiopsiesSkin Biopsies |
Who may qualify
- Ages
- 7 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
Key exclusion criteria (6 listed)
- For individuals undergoing blister or skin biopsy procedures, history of keloid formation.
- Current or prior (within 3 months) anticoagulant or anti-platelet therapy (other than aspirin or non-steroidal anti-inflammatory drugs [NSAIDs]).
- Current or prior (within 3 months) use of immunomodulatory drugs (e.g., chemotherapy, steroids), except if approved by the principal investigator.
- Pregnancy.
- Any condition that, in the opinion of the investigator, contraindicates participation in the study.
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 |
|---|---|---|
| Blister inductionBlister induction involves creating 8 blisters on the forearm and removing the tops of the blisters for primary cell culture derivation. After blister induction, subjects may have an optional overnight admission to assess cell infiltration in response to autologous serum and/or sterile saline solution. | Other | 1 |
| Skin BiopsiesThe skin biopsies will involve up to 4 biopsies: 2 initial punch biopsies 2 mm in diameter, followed by a punch biopsy 3 (plus or minus 1) and 7 (plus or minus 2) days later using a 3 mm punch to encompass the initial biopsy sites, capturing the tissue at 3 and 7 days of healing. | Other | 2 |
Primary outcome
Tumor necrosis factor alpha (TNFa) production by keratinocytes from patients with HIES versus healthy volunteers
Time frame: Throughout study
Evaluate epithelial cell responses to cutaneous wounds and infections of keratinocytes and other cutaneous epithelial cells in patients with HIES or CGD and healthy volunteers.
T-cell infiltration as percent of total cell infiltration in patients with CGD versus healthy volunteers.
Time frame: Throughout study
Identify cellular mediators that contribute to the inflammatory processthrough evaluation of infiltrating cell types.
Fold induction in genes related to wound healing.
Time frame: Throughout study
Determine whether there are abnormalities in specific tissue repair pathways, such as epithelial to mesenchymal transition (EMT).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Background: PubMed 17940231Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71. doi: 10.1001/jama.298.15.1763.
- Background: PubMed 14665659Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003 Dec 10;290(22):2976-84. doi: 10.1001/jama.290.22.2976.
- Background: PubMed 22282052Myles IA, Datta SK. Staphylococcus aureus: an introduction. Semin Immunopathol. 2012 Mar;34(2):181-4. doi: 10.1007/s00281-011-0301-9. Epub 2012 Jan 27. No abstract available.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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.
Ian A Myles, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Blister induction and Skin Biopsies in people with Hyper-Immunoglobulin E. Syndrome (HEIS) and Chronic Granulomatous Disease (CGD), run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 9 inclusion and 6 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: withdrawn, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Tumor necrosis factor alpha (TNFa) production by keratinocytes from patients with HIES versus healthy volunteers (time frame: Throughout study). The study lists 3 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 NCT03921515, which also lists 3 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 13 Dec 2024.