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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Comparison Between the Post-Treatment Reactions After Single-dose Ivermectin or DEC in Subjects With Loa Loa Infection

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. Parti

    Detailed Summary: Ivermectin is currently used for mass drug distribution for the control of onchocerciasis and elimination of lymphatic filariasis in Africa. Due to the occurrence of severe neurologic adverse events in individuals with concomitant Loa loa infection and high levels of circulating microfilariae, drug distribution has been halted in many areas in Cameroon, Democratic Republic of Congo and other Loa-endemic countries. Diethylcarbamazine citrate (DEC) is the treatment of choice for Loa loa infection in the United States and other non-endemic countries, but can also be associated with the development of severe adverse reactions, including fatal encephalopathy, that are correlated with the number of circulating microfilariae in the blood. The cause of these reactions is unknown, and it is not known if post-treatment reactions to DEC and ivermectin both have the same underlying mechanism. Post-treatment reactions to both medications are accompanied by a dramatic interleukin-5 (IL-5)-dependent increase in eosinophilia and evidence of eosinophil activation. Preliminary data suggests that, unlike post-treatment responses in Wolbachia-containing filariae, inflammatory mediators commonly seen in bacterial infections and malaria, including tumor necrosis factor (TNF)-alpha and IL-1-beta, are not increased post-treatment with DEC. The aim of this study is to characterize the immunologic mechanisms of ivermectin and DEC posttreatment reactions so that it can be established whether or not these posttreatment reactions have the same underlying mechanism. An understanding of the pathophysiology of these post-treatment reactions is necessary in order to develop strategies to prevent these reactions in the future. We plan to randomize 20 subjects with low- to- moderate numbers of circulating Loa loa microfilariae to receive a single oral dose of either ivermectin (200 mcg/kg) or DEC (8 mg/kg) in an inpatient setting in Cameroon. Signs and symptoms, blood microfilarial levels, complete b
    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome: The Peak % of Baseline Eosinophil Count Measured During the First 7 Days Post-treatment. [ Time Frame: 7 days ]

    Original Primary Outcome: The peak % change from baseline eosinophil count measured during the first 7 days post-treatment. [ Time Frame: 7 days ]

    Current Secondary Outcome:

    • The Frequency of Adverse Events [ Time Frame: 7 days ]
      Symptoms, signs and laboratory abnormalities occurring in the 7 days post-treatment
    • Eosinophil Activation [ Time Frame: 3 days ]
      Levels of surface marker expression on eosinophils
    • Proportion of Subjects Who Clear Microfilaremia [ Time Frame: 14 days ]


    Original Secondary Outcome:

    • The frequency and severity of adverse events [ Time Frame: 7 days ]
    • Markers of eosinophil activation, including levels of surface marker expression on eosinophils and serum levels of eosinophil granule proteins [ Time Frame: 7 days ]
    • Proportion of Subjects Who Clear Microfilaremia [ Time Frame: 14 days ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: May 5, 2012
    Date Started: April 2012
    Date Completion:
    Last Updated: September 20, 2016
    Last Verified: September 2016