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CompletedNCT03257072ReCHHI1Updated Nov 18, 2020

Repeated Controlled Human Hookworm Infection

An interventional study of 50 Necator americanus L3 larvae and 100 Necator americanus L3 larvae in Necator Americanus Infection, sponsored by Meta Roestenberg. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-11-18.

Sponsored by Meta Roestenberg · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

Twenty-four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus larvae for a maximum of three times.

Read the detailed description

Twenty-four volunteers will be allocated equally into three groups (i.e. group A, B, C). Group A, B, and C will have one, two, and three infections respectively. Every infection will be performed with 50 L3 Necator americanus larvae. Group A will receive infection at week 4 only. Group B will be infected at week 2 and week 4. Group C will be infected at week 0, 2 and 4. To maintain blinding, group A and B will receive mock infections with water at week 0 and week 0 and 2 respectively. The interval between each CHHI is 2 weeks. Before every infection, the safety will be assessed by a review of adverse events data with a local safety monitor.

Sixteen weeks after the last infection (week 20), all volunteers will be offered treatment with a 3-day regimen of albendazole to abrogate infection. Volunteers with average egg counts >250 eggs per gram will be asked if they would be willing to keep their infection for a maximum of two years (chronic donors). No more than four volunteers will be selected to be chronic donors. Six months after the last infection (or after the last donation for the chronic donors) volunteers will undergo their last visit.

02

Conditions studied

  • Necator Americanus Infection

Keywords

  • hookworm
  • controlled human infection model
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Subject is aged ≥ 18 and ≤ 45 years and in good health.
  2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
  3. Subject is able to communicate well with the investigator, is available to attend all study visits.
  4. Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
  5. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
  6. Subject has signed informed consent.

Exclusion criteria

Exclusion Criteria:

  1. 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:

    • Body Mass Index (BMI) \<18.0 or >30.0 kg/m2 at screening;
    • 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 \<10 ug/L, transferrine \<2.04 g/L or Hb \<7.0 mmol/L for females or \<8.0 mmol/L for males;
    • history of malignancy of any organ system (other than localized 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.
  2. Known hypersensitivity to or contra-indications for use of albendazole, including co-medication known to interact with albendazole metabolism (e.g. carbamazepine, phenobarbital, phenytoin, cimetidine, theophylline, dexamethasone)
  3. Known allergy to amphotericin B or gentamicin
  4. For female subjects: positive urine pregnancy test at screening
  5. Positive faecal qPCR or Kato-Katz for hookworm at screening, any known history of hookworm infection or treatment for hookworm infection or possible exposure to hookworm in the past
  6. Being an employee or student of the department of parasitology of the LUMC
  7. Current or past scars, tattoos, or other disruptions of skin integrity at the intended site of larval application
  8. Subjects with planned travel to hookworm endemic areas during this trial
  9. Receipt of a vaccine within 4 weeks prior to the study initiation
  10. Known food allergy
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
24 participants (actual)

Study arms

  • Experimental
    A: 50 Necator americanus L3 larvae

    Mock infections with water at week 0 and 2, infection with 50 Necator americanus L3 larvae at week 4

    Biological: 50 Necator americanus L3 larvae

  • Experimental
    B: 100 Necator americanus L3 larvae

    Mock infections with water at week 0, infection with 50 Necator americanus L3 larvae at week 2 and 4

    Biological: 100 Necator americanus L3 larvae

  • Experimental
    C: 150 Necator americanus L3 larvae

    Infection with 50 Necator americanus L3 larvae at week 0, 2 and 4

    Biological: 150 Necator americanus L3 larvae

Interventions

  • Biological50 Necator americanus L3 larvae

    1x50 Necator americanus L3 larvae

  • Biological100 Necator americanus L3 larvae

    2x50 Necator americanus L3 larvae

  • Biological150 Necator americanus L3 larvae

    3x50 Necator americanus L3 larvae

05

What researchers measure

Primary outcomes

  1. Frequency of adverse events

    Frequency of adverse events as compared between study groups A, B and C.

    Time frame: 28 weeks

  2. Magnitude of adverse events

    Magnitude of adverse events as compared between study groups A, B and C.

    Time frame: 28 weeks

Secondary outcomes

  1. Variability in egg secretion

    Variability in egg secretion by Kato-Katz from week 16 to 20

    Time frame: 20 weeks

  2. Lowest dose at which there is 100% patent hookworm infection

    The lowest dose at which there is 100% patent hookworm infection, as defined by a positive Kato-Katz at any time between week 16 to 20

    Time frame: 20 weeks

  3. Comparison of the average number of eggs secreted

    Comparison of the average number of eggs secreted by Kato-Katz and qPCR between different groups in weeks 16-20 after the infection

    Time frame: 20 weeks

06

Study locations

1 site
  • Leiden University Medical Center
    Leiden, 2333 ZA, Netherlands
07

References and documents

Publications

  • Hoogerwerf MA, Koopman JPR, Janse JJ, Langenberg MCC, van Schuijlenburg R, Kruize YCM, Brienen EAT, Manurung MD, Verbeek-Menken P, van der Beek MT, Westra IM, Meij P, Visser LG, van Lieshout L, de Vlas SJ, Yazdanbakhsh M, Coffeng LE, Roestenberg M. A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection. J Infect Dis. 2021 Mar 3;223(5):905-913. doi: 10.1093/infdis/jiaa414. PubMed 32645714 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03257072
Lead sponsor
Meta Roestenberg
Responsible party
Meta Roestenberg (Principal Investigator, Leiden University Medical Center) — Sponsor-investigator
First posted
Aug 22, 2017
Start date
Jan 10, 2018
Primary completion
Aug 30, 2018
Completion
Aug 30, 2018
Last update
Nov 18, 2020

Study contacts

Meta Roestenberg, MD. PhD.
principal investigator · LUMC

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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