Immune Responses in the Skin After Hookworm Infection

NCT06478498 | Not Yet Recruiting

• 1 other identifier: HibiSki
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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. Two of the volunteers will retain the infection for up to two years and will be asked to donate stool samples.

Conditions

Necator Americanus Infection

Keywords

Controlled human infection model; hookworm; immune responses; skin

Outcome Measures

Primary Outcomes (2)

• Identity of skin effector cells

  Identification of effector cells in the skin by Hyperion Imaging Mass Cytometry after repeated controlled hookworm infections

  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

  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

  6 weeks from start of the study

• Number of hookworm eggs in faeces after infection

  15-16 weeks after start of the study

Other Outcomes (1)

• Number of adverse events following exposure(s) to hookworm larvae

  12 weeks after last infection timepoint

Study Arms (2)

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.

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.

Biological: Necator americanus L3 larvae

Interventions

Necator americanus L3 larvae BIOLOGICAL

Necator americanus L3 larvae

Chronic donor group; Non-donor group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Subject has signed informed consent (note: there are different informed consent forms for group A- and 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

MeSH Terms

Conditions

Ancylostomiasis

Condition Hierarchy (Ancestors)

Hookworm Infections; Strongylida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Infectious Diseases and vaccine development

Model Details: 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.

Study Record Dates

• First Submitted: June 24, 2024
• First Posted: June 27, 2024
• Study Start: October 1, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)