Post-treatment Effects of Ivermectin (IVM) or Diethylcarbamazine (DEC) in Loiasis

NCT01593722 | Completed Phase 4 Results DMC

• 2 other identifiers: 99991211712-I-N117
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Loa loa is a small worm that infects people in West and Central Africa. It is spread by the bite of a fly. Adult worms live under the skin and can cause swelling in the arms, legs, and face. Some people have more serious infections in the heart, kidneys, or brain. Most people with Loa loa infection have no symptoms at all. The standard treatment for Loa loa infection is a medicine called diethylcarbamazine (DEC). Some people have bad reactions to DEC, including itching, muscle pains, and in severe cases coma and death.
• Another drug, ivermectin, is used in mass drug treatment programs to prevent the spread of worm infections that cause blindness and massive swelling (elephantiasis). However, people who also have Loa loa have had serious bad reactions to ivermectin. Researchers want to study both DEC and ivermectin to find out why these reactions occur. If they can be prevented, mass drug treatment programs will be able to be used in areas in Africa where Loa loa exists. Objectives: \- To study the side effects of DEC and ivermectin treatment for Loa loa infection. Eligibility: \- Individuals who live in 4 villages in Cameroon where Loa loa infection is known to exist, who are between 20 and 60 years of age, not pregnant or breastfeeding and have a low level of Loa loa parasites in the blood, but are otherwise healthy. Design:
• Participants will be screened with a physical exam and medical history. Blood samples will be collected to check for Loa loa infection. Participants will also have an eye exam and provide skin samples to check for other worm infections that may interfere with the study treatment.
• Participants will be admitted to the hospital for 4 days (during and after the treatment). They will receive a single dose of either DEC or ivermectin.
• After treatment, regular blood samples will be collected. Participants will be asked questions about how they feel after treatment. Physical exams will be performed. If side effects develop, participants will be treated at the hospital.
• After leaving the hospital, participants will have followup visits. These visits will happen on days 5, 7, 9, and 14 after receiving the study medicine. They will involve a short physical exam and collection of blood samples.
• At the end of the study, participants will be offered a full 21-day DEC treatment to cure the Loa loa infection.

Conditions

Loiasis

Keywords

Loa loa; Immune Response; Therapy

Outcome Measures

Primary Outcomes (1)

• The Peak % of Baseline Eosinophil Count Measured During the First 7 Days Post-treatment.

  7 days

Secondary Outcomes (3)

• The Frequency of Adverse Events

  7 days

• Eosinophil Activation

  3 days

• Proportion of Subjects Who Clear Microfilaremia

  14 days

Other Outcomes (1)

• Treatment Efficacy

  6 months

Study Arms (2)

diethylcarbamazine

ACTIVE COMPARATOR

diethylcarbamazine 8 mg/kg single oral dose

Drug: Diethylcarbamazine

ivermectin

ACTIVE COMPARATOR

ivermectin 200 mcg/kg single oral dose

Drug: Ivermectin

Interventions

Diethylcarbamazine DRUG

single dose

Also known as: Hetrazan, Banocide

diethylcarbamazine

Ivermectin DRUG

single dose

Also known as: Mectizan, Stromectol

ivermectin

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A subject will be eligible for participation in the screening portion of this protocol if all of the following criteria apply:
• male or non-pregnant and not breastfeeding female subjects,
• age 20-60 years (per participant self-report)
• resident of Akonolinga
• Loa microfilaremia from 20 to 5000 mf/mL from the prior screening in the village or did not participate in the prior screening
• consent to a blood draw to screen for infection with Loa loa
• must be willing to have blood samples stored

You may not qualify if:

• A subject will not be eligible for participation in the screening portion of this study if any of the following conditions apply:
• Known to be pregnant (by history) or breastfeeding
• Chronic medical conditions, including but not limited to diabetes, renal or hepatic insufficiency, immunodeficiency, psychiatric disorder, seizure, that in the investigators judgments are deemed to be clinically significant
• History of hypersensitivity reaction to DEC or IVM
• Loa loa microfilaremia between 20 and 2,000 mf/mL blood drawn between 11:30 am and 2:30 pm measured within 30 days prior to the baseline visit
• The subject agrees to storage of samples for study
• A subject will not be eligible to participate in the interventional portion of the study if any of the following conditions are fulfilled at the time of enrollment:
• Pregnancy (by serum or urine beta-HCG) or breastfeeding
• Chronic kidney or liver disease
• Hgb \< 10 gm/dL
• Filarial infection other than Loa loa or M. perstans (O. volvulus, or W. bancrofti)
• Use of DEC or IVM within the past 6 months
• Use of immunosuppressive therapies, including steroids, within the past month
• Any condition that in the investigator s opinion places the subject at undue risk by participating in the study
• Pregnant women and children (the age of consent in Cameroon is 20 years of age) will be excluded from this study since it involves administration of medications contraindicated in pregnancy and more than minimal risk with no prospect of direct benefit, respectively.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Filariasis and other Tropical Diseases Research Center

Yaoundé, Cameroon

Location

Related Publications (4)

• Klion AD, Massougbodji A, Sadeler BC, Ottesen EA, Nutman TB. Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. J Infect Dis. 1991 Jun;163(6):1318-25. doi: 10.1093/infdis/163.6.1318.

  PMID: 2037798 BACKGROUND

• Boussinesq M. Loiasis. Ann Trop Med Parasitol. 2006 Dec;100(8):715-31. doi: 10.1179/136485906X112194.

  PMID: 17227650 BACKGROUND

• Winkler S, Paiha S, Winkler H, Graninger W, Marberger M, Steiner GE. Microfilarial clearance in loiasis involves elevation of Th1 and Th2 products and emergence of a specific pattern of T-cell populations. Parasite Immunol. 1996 Sep;18(9):479-82. doi: 10.1111/j.1365-3024.1996.tb01032.x.

  PMID: 9226684 BACKGROUND

• Herrick JA, Legrand F, Gounoue R, Nchinda G, Montavon C, Bopda J, Tchana SM, Ondigui BE, Nguluwe K, Fay MP, Makiya M, Metenou S, Nutman TB, Kamgno J, Klion AD. Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection. Clin Infect Dis. 2017 Apr 15;64(8):1017-1025. doi: 10.1093/cid/cix016.

  PMID: 28329346 DERIVED

MeSH Terms

Conditions

Loiasis

Interventions

Diethylcarbamazine; Ivermectin

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Macrolides; Polyketides; Lactones

Limitations and Caveats

Small number of subjects analyzed

Results Point of Contact

• Title: Dr. Amy Klion
• Organization: Laboratory of Parasitic Diseases, NIAID, NIH

aklion@niaid.nih.gov

301-435-8903

Study Officials

• Amy D Klion, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2012
• First Posted: May 8, 2012
• Study Start: April 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: January 1, 2014
• Last Updated: November 9, 2016
• Results First Posted: November 9, 2016

Record last verified: 2016-09

Locations

CA (1)