Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial.
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 random...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0007966 |
| _version_ | 1818581565479845888 |
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| author | Michel Mandro Joseph Nelson Siewe Fodjo Deby Mukendi Alfred Dusabimana Sonia Menon Steven Haesendonckx Richard Lokonda Swabra Nakato Francoise Nyisi Germain Abhafule Deogratias Wonya'Rossi Jean Marie Jakwong Patrick Suykerbuyk Jacques Meganck An Hotterbeekx Robert Colebunders |
| author_facet | Michel Mandro Joseph Nelson Siewe Fodjo Deby Mukendi Alfred Dusabimana Sonia Menon Steven Haesendonckx Richard Lokonda Swabra Nakato Francoise Nyisi Germain Abhafule Deogratias Wonya'Rossi Jean Marie Jakwong Patrick Suykerbuyk Jacques Meganck An Hotterbeekx Robert Colebunders |
| author_sort | Michel Mandro |
| collection | DOAJ |
| description | 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 onchocerciasis-infected 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 treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits. CONCLUSION:Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE. TRIAL REGISTRATION:Registration: www.clinicaltrials.gov; NCT03052998. |
| first_indexed | 2024-12-16T07:35:31Z |
| format | Article |
| id | doaj.art-577599405307437ea164259e56940717 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-16T07:35:31Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-577599405307437ea164259e569407172022-12-21T22:39:14ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-01-01141e000796610.1371/journal.pntd.0007966Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial.Michel MandroJoseph Nelson Siewe FodjoDeby MukendiAlfred DusabimanaSonia MenonSteven HaesendonckxRichard LokondaSwabra NakatoFrancoise NyisiGermain AbhafuleDeogratias Wonya'RossiJean Marie JakwongPatrick SuykerbuykJacques MeganckAn HotterbeekxRobert ColebundersINTRODUCTION: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 onchocerciasis-infected 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 treatment and being seizure-free at month 4 (OR: 1.652, 95% CI 0.975-2.799; p = 0.062). There was no significant difference in the probability of experiencing >50% reduction of the seizure frequency at month 4 between the two treatment arms. Also, treatment with ivermectin did not significantly increase the odds of being seizure-free during the individual follow-up visits. CONCLUSION:Whether ivermectin has an added value in reducing the frequency of seizures in PWE treated with AED remains to be determined. A larger study in persons with OAE on a stable AED regimen and in persons with recent epilepsy onset should be considered to further investigate the potential beneficial effect of ivermectin treatment in persons with OAE. TRIAL REGISTRATION:Registration: www.clinicaltrials.gov; NCT03052998.https://doi.org/10.1371/journal.pntd.0007966 |
| spellingShingle | Michel Mandro Joseph Nelson Siewe Fodjo Deby Mukendi Alfred Dusabimana Sonia Menon Steven Haesendonckx Richard Lokonda Swabra Nakato Francoise Nyisi Germain Abhafule Deogratias Wonya'Rossi Jean Marie Jakwong Patrick Suykerbuyk Jacques Meganck An Hotterbeekx Robert Colebunders Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. PLoS Neglected Tropical Diseases |
| title | Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. |
| title_full | Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. |
| title_fullStr | Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. |
| title_full_unstemmed | Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. |
| title_short | Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. |
| title_sort | ivermectin as an adjuvant to anti epileptic treatment in persons with onchocerciasis associated epilepsy a randomized proof of concept clinical trial |
| url | https://doi.org/10.1371/journal.pntd.0007966 |
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