Clinical Trial: Ivermectin Treatment in Patients With Onchocerciasis-associated Epilepsy

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Ivermectin Treatment in Patients With Onchocerciasis-associated Epilepsy: A Randomized Clinical Trial

Brief Summary:

Many studies have reported an association between epilepsy, including 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

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 be an extra argument that Onchocerciasis is causing epilepsy and that therefore we should increase our efforts to eliminate onchocerciasis.

Methods

We will conduct a randomized clinical trial in the Democratic Republic of Congo (DRC) to compare seizure freedom in onchocerciasis infested epilepsy patients who receive immediate Ivermectin treatment with delayed (after four months) Ivermectin treatment. All participants will simultaneously receive anti-epileptic drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the fourth 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 non-Ivermectin arms.

Current status

Detailed Summary:

Introduction

Many studies have reported an association between epilepsy, including nodding syndrome (NS), and onchocerciasis. A meta-analysis of African population-based surveys showed a variation in epilepsy prevalence consistent with onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence. NS is an epileptic disorder occurring in children in onchocerciasis (river blindness) endemic regions, initially only observed in South Sudan, Uganda and Tanzania. NS occurs in previously health children, aged mainly between 5-18 years and is characterized by head-nodding, an atonic epileptic seizure. Individuals may also develop other types of seizures and stunted growth. NS should be considered part of a spectrum of onchocerciasis associated epileptic (OAE) disorders. We recently suggested that these epileptic disorders share etiological factors related to Onchocerca volvulus (OV) infection and therefore considered Ivermectin, used to treat Onchocerciasis, as a treatment option for OAE.

One dose of Ivermectin eliminates microfilariae very rapidly. A mathematical model predicted that microfilariaedermia would be reduced by half 24 h after the intake of Ivermectin. Therefore, if the microfilariae load plays an important role in causing OAE, it may be that Ivermectin also has a rapid effect on the frequency of seizures.

Ivermectin treatment may decrease seizure frequency in patients with OAE In a study in Kabarole district in Uganda in 1992, 34/91 (37%) patients reported some decrease in either the frequency or severity of seizures after one dose of Ivermectin (150 µg/kg). After being treated with Ivermectin, 13 (14%) individuals had no seizures for 3.7 months (on average). Seizures were unchanged in
Sponsor: Robert Colebunders

Current Primary Outcome: seizure freedom [ Time Frame: 4 months ]

absence of seizures month 4


Original Primary Outcome: Same as current

Current Secondary Outcome: >50 % reduction in seizure frequency [ Time Frame: 4 months ]

>50 % reduction in seizure frequency compared to baseline


Original Secondary Outcome: Same as current

Information By: Universiteit Antwerpen

Dates:
Date Received: February 10, 2017
Date Started: April 1, 2017
Date Completion: February 1, 2018
Last Updated: February 15, 2017
Last Verified: February 2017