Repeated Controlled Human Hookworm Infection

Necator Americanus Infection Clinical Trial

— ReCHHI1  

Official title:

Repeated Controlled Human Hookworm Infection in Healthy Dutch Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03257072
• Other study ID #: ReCHHI1
• Status: Completed
• Phase: N/A
• Start date: January 10, 2018
• Est. completion date: August 30, 2018

Study information

• Verified date: November 2020
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 30, 2018
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Hookworm Infections
• Infection
• Necator Americanus Infection

Intervention

Biological:
• 50 Necator americanus L3 larvae
1x50 Necator americanus L3 larvae
• 100 Necator americanus L3 larvae
2x50 Necator americanus L3 larvae
• 150 Necator americanus L3 larvae
3x50 Necator americanus L3 larvae

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Meta Roestenberg

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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 rand — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events	Frequency of adverse events as compared between study groups A, B and C.	28 weeks
Primary	Magnitude of adverse events	Magnitude of adverse events as compared between study groups A, B and C.	28 weeks
Secondary	Variability in egg secretion	Variability in egg secretion by Kato-Katz from week 16 to 20	20 weeks
Secondary	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
Secondary	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