Necator Americanus InfectionHiBiSkiNCT06478498
Immune Responses in the Skin After Hookworm Infection
A study testing Necator americanus L3 larvae in people with Necator Americanus Infection, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Five healthy volunteers will be repeatedly exposed to L3 Necator americanus larvae after which two skin biopsies will be taken. Three of the volunteers will be treated two weeks after each infection after which the study will end after 13 weeks. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Necator Americanus Infection
- What is being tested?
- Necator americanus L3 larvae
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Oct 2024to Oct 2026
- Phase
- Interventional
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Subject is aged ≥ 18 and ≤ 45 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator, is available to attend all study visits.
- Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
- Subject agrees to refrain from travel to a hookworm endemic area during the course of the trial.
Show all 13Show fewer
- Subject has signed informed consent (note: there are different informed consent forms for group A- and B participants).
- Additional inclusion criteria for group B participants:
- Agrees to remain infected and to commit to study procedures and rules
- Agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
- Agrees to refrain from travel to a hookworm endemic area during the course of the trial.
- Minimum egg output of 1500 epg at the start of the donor phase.
- Does not meet any of the criteria for withdrawal outlined in section 8.4.
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:
- positive HIV, HBV or HCV screening tests;
- the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period;
- having one of the following laboratory abnormalities: ferritine <10ug/L, transferrine <2.04g/L or Hb <6.5 mmol/L for females or <7.5 mmol/L for males.
- history of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
Show all 23Show fewer
- any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
- history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset;
- inflammatory bowel syndrome;
- regular constipation, resulting in bowel movements less than three times per week.
- Known hypersensitivity to or contra-indications for use of albendazole, including comedication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone).
- Known allergy to amphotericin B or gentamicin.
- For female subjects: positive urine pregnancy test at screening
- Positive faecal qPCR for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection.
- Being an employee or student of the study team.
- Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application.
- increased risk of complications after skin biopsy (e.g. use of anticoagulants, immunosuppressive medication or having tattoo's in the biopsy region).
- Any condition or situation that could influence the independent consent of participant (e.g. being a direct colleague or family member of study personnel).
- Any other condition or situation that would, in the opinion of the investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol or would compromise the integrity of the data.
- Additional exclusion criteria for group B participants:
- For female subjects: pregnancy as determined by positive urine hCG measured before stool donation.
- Having one of the following laboratory abnormalities: ferritin <10ug/L, transferrin <2.04g/L or Hb <7.0mmol/L for females or <8.0mmol/L for males.
- Positive HIV, HBV or HCV screening tests before donation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigating the Local Immune Responses in the Skin After Repeated Hookworm Infection
Five healthy volunteers will be repeatedly exposed to L3 Necator americanus larvae after which two skin biopsies will be taken. Three of the volunteers will be treated two weeks after each infection after which the study will end after 13 weeks. Two of the volunteers will retain the infection for up to two years and will be asked to donate stool samples.
Read the detailed description
Five volunteers will be exposed to 50 Necator americanus L3 larvae, after which they will be treated with a curative regimen of albendazole after two weeks. Then, they will be inoculated with a lower dose of 10 L3 larvae concentrated on one spot, followed by two skin biopsies (one at the inoculation site, the other one serving as a negative control). Subsequently, participants will be treated with albendazole at week 5, except for the participants who have volunteered to become chronic donors. For chronic donors, patency of infection will be assessed and infections repeated (max dose 50 L3 larvae at one time) until egg outputs are >1500 eggs per gram (epg) at the start of the donor phase. If necessary, top-up inoculations can be performed in the donor phase as well when the egg-output is too low for the requested experiments.
- Conditions
- Necator Americanus Infection
- Being tested
- Necator americanus L3 larvae
- Keywords
- Controlled human infection model, hookworm, immune responses, skin
- Medical subject headings
- Ancylostomiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Necator americanus L3 larvaeBiological
Necator americanus L3 larvae
| Study group | Role | What they receive |
|---|---|---|
| Non-donor group | Experimental | Three healthy hookworm-naive volunteers will be infected with 50 Necator americanus L3 larvae in week 0, receive treatment in week 2, followed by another inoculation with 10 Necator americanus L3 larvae localised on one spot after which two biopsies will be taken (one from each arm). After this, they will be treated in week 5. The study ends in week 13. Receives: Biological: Necator americanus L3 larvae |
| Chronic donor group | Experimental | Two healthy hookworm-naive volunteers will be infected with 50 Necator americanus L3 larvae in week 0, receive treatment in week 2, followed by another inoculation with 10 Necator americanus L3 larvae localised on one spot after which two biopsies will be taken (one from each arm). After this, they receive additional inoculations (maximal dose 50 L3 larvae at one time) until egg outputs are >1500 epg at the start of the donor phase.
In the donor phase, volunteers will be asked to donate faeces regularly (~ 5 -10 times a year). Safety visits are scheduled at month 12 and 24. The study ends after approximately 2 years. Receives: Biological: Necator americanus L3 larvae |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identity of skin effector cells
Identification of effector cells in the skin by Hyperion Imaging Mass Cytometry after repeated controlled hookworm infections
Measured: 3 weeks + 1 day after initial infection (timepoint of taking the biopsies)
Correlation between macroscopic skin response and effector cells
Association between the macroscopic skin reaction and effector cells present identified by Hyperion Imaging Mass Cytometry
Measured: 3 weeks + 1 day after initial infection (timepoint of taking the biopsies)
Secondary outcomes (2)
Measurement of humoral (antibody responses and cytokines) and cellular immunological changes after controlled hookworm infections
Measured: 6 weeks from start of the study
Number of hookworm eggs in faeces after infection
Detection of hookworm eggs by faeces microscopy (Kato-Katz) at week 15-16 in volunteers who volunteered to be chronic donors
Measured: 15-16 weeks after start of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2024
- Study start1 Oct 2024 (estimated)
- Primary completion1 Jan 2025 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Necator Americanus InfectionStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Two groups who will follow similar study procedures up until week 5. After this, one group receives direct treatment after which the study will end in week 13. The other group receives top-up inoculations to receive patent infection and remains chronically infected for approximately two years, therefore their follow-up scheme looks different compared to the other group.
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meta Roestenberg, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06478498
- Sponsor's protocol ID
- HibiSki
- Acronym
- HiBiSki
- Status last verified
- Jul 2024
- First submitted
- 24 Jun 2024
- Last updated
- 12 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Local Immune Responses in the Skin After Repeated Hookworm Infection
- ClinicalTrials.gov ID
- NCT06478498
- Acronym / sponsor ID
- HiBiSki / HibiSki
- Conditions
- Necator Americanus Infection
- Keywords
- Controlled human infection model, hookworm, immune responses, skin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 27 Jun 2024 (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.
Five healthy volunteers will be repeatedly exposed to L3 Necator americanus larvae after which two skin biopsies will be taken. Three of the volunteers will be treated two weeks after each infection after which the study will end after 13 weeks. Two of the volunteers will retain the infection for up to two years and will be asked to donate stool samples.
Detailed description
Five volunteers will be exposed to 50 Necator americanus L3 larvae, after which they will be treated with a curative regimen of albendazole after two weeks. Then, they will be inoculated with a lower dose of 10 L3 larvae concentrated on one spot, followed by two skin biopsies (one at the inoculation site, the other one serving as a negative control). Subsequently, participants will be treated with albendazole at week 5, except for the participants who have volunteered to become chronic donors. For chronic donors, patency of infection will be assessed and infections repeated (max dose 50 L3 larvae at one time) until egg outputs are >1500 eggs per gram (epg) at the start of the donor phase. If necessary, top-up inoculations can be performed in the donor phase as well when the egg-output is too low for the requested experiments.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two groups who will follow similar study procedures up until week 5. After this, one group receives direct treatment after which the study will end in week 13. The other group receives top-up inoculations to receive patent infection and remains chronically infected for approximately two years, therefore their follow-up scheme looks different compared to the other group.
| Arm | Type | Receives |
|---|---|---|
| Non-donor group | Experimental | Biological: Necator americanus L3 larvaeThree healthy hookworm-naive volunteers will be infected with 50 Necator americanus L3 larvae in week 0, receive treatment in week 2, followed by another inoculation with 10 Necator americanus L3 larvae localised on one spot after which two biopsies will be taken (one from each arm). After this, they will be treated in week 5. The study ends in week 13. |
| Chronic donor group | Experimental | Biological: Necator americanus L3 larvaeTwo healthy hookworm-naive volunteers will be infected with 50 Necator americanus L3 larvae in week 0, receive treatment in week 2, followed by another inoculation with 10 Necator americanus L3 larvae localised on one spot after which two biopsies will be taken (one from each arm). After this, they receive additional inoculations (maximal dose 50 L3 larvae at one time) until egg outputs are >1500 epg at the start of the donor phase. In the donor phase, volunteers will be asked to donate faeces regularly (~ 5 -10 times a year). Safety visits are scheduled at month 12 and 24. The study ends after approximately 2 years. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Subject is aged ≥ 18 and ≤ 45 years and in good health.
- Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
- Subject is able to communicate well with the investigator, is available to attend all study visits.
- Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
Key exclusion criteria (23 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following:
- Known hypersensitivity to or contra-indications for use of albendazole, including comedication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone).
- Known allergy to amphotericin B or gentamicin.
- For female subjects: positive urine pregnancy test at screening
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 |
|---|---|---|
| Necator americanus L3 larvaeNecator americanus L3 larvae | Biological | Chronic donor group, Non-donor group |
Primary outcome
Identity of skin effector cells
Time frame: 3 weeks + 1 day after initial infection (timepoint of taking the biopsies)
Identification of effector cells in the skin by Hyperion Imaging Mass Cytometry after repeated controlled hookworm infections
Correlation between macroscopic skin response and effector cells
Time frame: 3 weeks + 1 day after initial infection (timepoint of taking the biopsies)
Association between the macroscopic skin reaction and effector cells present identified by Hyperion Imaging Mass Cytometry
2 secondary outcomes
Measurement of humoral (antibody responses and cytokines) and cellular immunological changes after controlled hookworm infections
Time frame: 6 weeks from start of the study
Number of hookworm eggs in faeces after infection
Time frame: 15-16 weeks after start of the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Necator Americanus Infection
RecruitingPhase 1
Experimental Infection of Hookworm-naïve Adults With Dermally-applied Infectious Necator Americanus Hookworm Larvae
Hookworm Infection
Active, not recruiting
Cement flooRs AnD chiLd hEalth (CRADLE)
Ascaris Lumbricoides Infection, Necator Americanus Infection
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Necator americanus L3 larvae in people with Necator Americanus Infection, run by Leiden University Medical Center at 1 site in Netherlands.
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 13 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 12 Jul 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 Netherlands. 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?
Results are not available in the source record.
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?
Identity of skin effector cells (time frame: 3 weeks + 1 day after initial infection (timepoint of taking the biopsies)). 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?
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 12 Jul 2024.