Repeated Controlled Human Hookworm Infection (ReCHHI1)

Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers

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

Study Overview

• Status: Completed
• Conditions: Necator Americanus Infection
• Intervention / Treatment: Biological: 50 Necator americanus L3 larvae; Biological: 100 Necator americanus L3 larvae; Biological: 150 Necator americanus L3 larvae

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• 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: Yes
• Genders Eligible for Study: All

Description

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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 1x50 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; 2x50 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; 3x50 Necator americanus L3 larvae

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Frequency of adverse events as compared between study groups A, B and C.	28 weeks
Magnitude of adverse events	Magnitude of adverse events as compared between study groups A, B and C.	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in egg secretion	Variability in egg secretion by Kato-Katz from week 16 to 20	20 weeks
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	20 weeks
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	20 weeks

Collaborators and Investigators

• Sponsor: Meta Roestenberg
• Investigators: Principal Investigator: Meta Roestenberg, MD. PhD., LUMC

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): August 30, 2018

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

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: ReCHHI1

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