Establishing a Controlled Human Hookworm Infection Model at Leiden University Medical Center (CHHIL)

Four healthy hookworm-naive volunteers will be exposed to 50 L3 Necator americanus larvae once and will retain infection for up to 2 years.

Study Overview

• Status: Completed
• Conditions: Necator Americanus Infection
• Intervention / Treatment: Biological: Necator americanus L3 larvae

Detailed Description

Four volunteers will be exposed to 50 Necator americanus L3 larvae. Volunteers will be followed on a weekly basis until week 12 after infection. If volunteers develop a patent infection, defined by detectable egg production in stool by microscopy at any timepoint within week 9 to 12, they will be scheduled to donate faeces on request.

Two years after infection or if volunteers do not excrete eggs detectable by microscopy on week 9 to 12, volunteers will be treated with a 3-day regimen of albendazole to abrogate the infection. Retreatment with albendazole will be given to volunteers who remain positive for hookworm after treatment.

Six months after the treatment, volunteers will undergo their last visit.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

1. Subject is aged ≥ 18 and ≤ 45 years.
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. Subjects are able to respond to phone or email within 24 hours during the first 12 weeks of the study.
5. Subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period.
6. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
7. Subject has signed informed consent

A potential subject who meets any of the following criteria will be excluded from participation in this study:

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:

   • history of severe asthma or other health conditions that may require future steroid use;
   • body weight <50 kg or 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 <7.5 mmol/L for females or <8.5 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 type 1 hypersensitivity to amphotericin B or gentamicin.
4. For female subjects: positive urine pregnancy test at screening.
5. Positive faecal PCR 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 with a stay in non-hygienic environment during this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Four healthy hookworm-naive volunteers will be infected with 50 Necator americanus L3 larvae.	Biological: Necator americanus L3 larvae; 50 Necator americanus L3 larvae

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of hookworm eggs by faeces microscopy (Kato-Katz) at any week between week 9 to 12 post-infection.	Detection of hookworm eggs by faeces microscopy (Kato-Katz) at any week between week 9 to 12 post-infection.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events following single exposure to hookworm larvae	Number of adverse events following single exposure to hookworm larvae	2 years
Humoral (antibody) and cellular immunological changes after controlled human hookworm infection	Humoral (antibody) and cellular immunological changes after controlled human hookworm infection	2 years
Time to positive faeces test for hookworm as defined by Kato-Katz and qPCR	Time to positive faeces test for hookworm as defined by Kato-Katz and qPCR	12 weeks

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Meta Roestenberg, MD, PhD, LUMC

Publications and helpful links

General Publications

• Hoogerwerf MA, Coffeng LE, Brienen EAT, Janse JJ, Langenberg MCC, Kruize YCM, Gootjes C, Manurung MD, Dekker M, Becker L, Erkens MAA, van der Beek MT, Ganesh MS, Feijt C, Winkel BMF, Westra IM, Meij P, Loukas A, Visser LG, de Vlas SJ, Yazdanbakhsh M, van Lieshout L, Roestenberg M. New Insights Into the Kinetics and Variability of Egg Excretion in Controlled Human Hookworm Infections. J Infect Dis. 2019 Aug 9;220(6):1044-1048. doi: 10.1093/infdis/jiz218.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): August 15, 2017
• Study Completion (Actual): November 22, 2021

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: hookworm; controlled human infection model
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Strongylida Infections; Infections; Communicable Diseases; Hookworm Infections; Ancylostomiasis
• Other Study ID Numbers: CHHIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No