Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial

Abstract

Introduction Recent findings from onchocerciasis-endemic foci uphold that increasing ivermectin coverage reduces the epilepsy incidence, and anecdotal evidence suggests seizure frequency reduction in persons with onchocerciasis-associated epilepsy, when treated with ivermectin. We conducted a randomized clinical trial to assess whether ivermectin treatment decreases seizure frequency. Methods A proof-of-concept randomized clinical trial was conducted in the Logo health zone in the Ituri province, Democratic Republic of Congo, to compare seizure frequencies in onchocerciasisinfected persons with epilepsy (PWE) randomized to one of two treatment arms: the anti-epileptic drug phenobarbital supplemented with ivermectin, versus phenobarbital alone. The primary endpoint was defined as the probability of being seizure-free at month 4. A secondary endpoint was defined as >50% reduction in seizure frequency at month 4, compared to baseline. Both endpoints were analyzed using multiple logistic regression. In longitudinal analysis, the probability of seizure freedom during the follow-up period was assessed for both treatment arms by fitting a logistic regression model using generalized estimating equations (GEE). Results Ninety PWE enrolled between October and November 2017 were eligible for analysis. A multiple logistic regression analysis showed a borderline association between ivermectin

Ivermectin Treatment Response in Two Rural Villages with a High Prevalence of Onchocerciasis and Epilepsy, Mahenge Tanzania

“…There is anecdotal evidence that ivermectin in O. volvulus infected PWE may decrease the frequency of seizures [27]. Moreover, a recent randomised clinical trial in DRC showed that O. volvulus infected PWE who received multiple doses of ivermectin were more likely to be seizure-free during the last four months of a one year trial than O. volvulus PWE who received only one dose of ivermectin [28]. The small sample size of our study and the low mf density at baseline, most likely explains why a bene cial effect of ivermectin was not observed.…”

OV16 Seroprevalence among Persons with Epilepsy in Onchocerciasis Endemic Regions: A Multi-Country Study

“…In Mahenge, Ulanga district, Tanzania [ 10 , 11 ], CDTI had been implemented for more than 20 years, Kitgum and Pader districts, Uganda [ 5 ], CDTI had been implemented since 2009, and in Cameroon, in Bilomo (Mbam valley), mass drug administration of ivermectin was implemented in 1998 and around mid-1990s in Kelleng (Sanaga valley) [ 12 ]. Other PWE were enrolled during the screening of PWE for participation in a clinical trial to investigate the effect of ivermectin on the frequency of seizures in persons with O. volvulus infection in the Logo health zone, Ituri province, Democratic Republic of Congo (DRC) [ 13 ]. In the Logo health zone, CDTI had never been implemented [ 14 ].…”

Single versus Multiple Dose Ivermectin Regimen in Onchocerciasis-Infected Persons with Epilepsy Treated with Phenobarbital: A Randomized Clinical Trial in the Democratic Republic of Congo

“…A multiple logistic regression analysis showed a borderline insignificant association at 5% significance level between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062) [9]. Given the small sample size, the results of the trial were difficult to interpret [9]. During the trial, we realized that the planned sample size (110 individuals) could not be reached as the inclusion criteria were very strict.…”

“…Ninety-four of them who met the criteria for onchocerciasis-associated epilepsy (OAE) [8], and who experienced at least two seizures per month by the time of assessment, were enrolled in a four-month proof-of-concept trial. A multiple logistic regression analysis showed a borderline insignificant association at 5% significance level between ivermectin treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062) [9]. Given the small sample size, the results of the trial were difficult to interpret [9].…”