Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

JMIR Res Protoc. 2017 Aug 30;6(8):e137. doi: 10.2196/resprot.7186.

Abstract

Background: Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences.

Objective: The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis.

Methods: We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms.

Results: Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018.

Conclusions: If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa-endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa.

Trial registration: ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0).

Keywords: Democratic Republic of the Congo; epilepsy; ivermectin; nodding syndrome; onchocerciasis; randomized clinical trial.

Associated data

  • ClinicalTrials.gov/NCT03052998