Post-treatment Effects of Ivermectin (IVM) or Diethylcarbamazine (DEC) in Loiasis
Condition: Loiasis
MeSH terms: Loiasis
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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 blood counts, intracellular and serum cytokine levels and
      markers of eosinophil activation will be assessed at baseline, 4 and 8 hours, and 1, 2, 3, 5,
      7, and 9 and 14 days post-treatment and compared between the two treatment groups. Subjects
      who received ivermectin will be treated with single dose DEC (8 mg/kg) on day 14. All
      subjects will then be followed at 6 and 12 months post-hospitalization to determine whether
      they have experienced Loa-specific symptoms (eyeworm or Calabar swellings). Mf count and
      complete blood count (CBC) with differential will be obtained at each follow-up visit.
      Subjects with Loa-specific symptoms or mf counts > 100 mf/mL at the 6 month time point will
      be offered a full treatment course. If > 50% of subjects meet criteria for full DEC treatment
      at the 6, month time point, all subjects will be treated and the study will enter a follow-up
      phase with a visit at 12 months (6 months after the full treatment course ).
    

Intervention name(s): Diethylcarbamazine; Ivermectin
Intervention type(s): Drug; Drug
Intervention description(s): single dose; single dose
Other intervention name(s): Hetrazan, Banocide; Mectizan, Stromectol
Intervention MeSH terms: Ivermectin; Diethylcarbamazine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Loa loa; Immune Response; Therapy