Ivermectin Treatment in Patients With Onchocerciasis-associated Epilepsy

NCT03052998 | Completed Phase 4 DMC

• 2 other identifiers: B300201730821ERC grant No.671055
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

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 Start of enrolment is planned from March 2017 and we expect to have enrolled all 110 participants by August 2017. Results are expected early 2018. Discussion 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 socio-economic status of families with affected members in Africa.

Conditions

Ivermectin; Onchocerciasis; Epilepsy

Outcome Measures

Primary Outcomes (1)

• seizure freedom

  absence of seizures month 4

  4 months

Secondary Outcomes (1)

• >50 % reduction in seizure frequency

  4 months

Study Arms (2)

Ivermectin

ACTIVE COMPARATOR

Ivermectin and anti-epileptic treatment

Drug: Ivermectin

no treatment

NO INTERVENTION

only anti-epileptic treatment

Interventions

Ivermectin DRUG

Effect of Ivermectin on frequency of seizures

Also known as: anti-epileptic drugs

Ivermectin

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 5 years and above
• Signed informed consent form
• Normal neurological development until onset of epilepsy
• Onset of epilepsy between ages of 5 and 18 years
• Seizure frequency of ≥2 seizures per month
• Presence of microfilaria in skin snip and/or antibodies against Ov16

You may not qualify if:

• Ivermectin intake the last 9 months
• Pregnancy or breastfeeding
• Known or suspected allergy to Ivermectin
• Loa Loa microfilariae in blood
• Epilepsy with known cause (e.g. severe head trauma, perinatal asphyxia, patients with a history of cerebral malaria, meningitis or encephalitis)

Sponsors & Collaborators

• Robert Colebunders: lead

Study Sites (1)

Centre de Recherche en Maladies Tropicales de l'Ituri

Rethy, Ituri, Democratic Republic of the Congo

Location

Related Publications (3)

• Mandro M, Siewe Fodjo JN, Mukendi D, Dusabimana A, Menon S, Haesendonckx S, Lokonda R, Nakato S, Nyisi F, Abhafule G, Wonya'Rossi D, Jakwong JM, Suykerbuyk P, Meganck J, Hotterbeekx A, Colebunders R. Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. PLoS Negl Trop Dis. 2020 Jan 10;14(1):e0007966. doi: 10.1371/journal.pntd.0007966. eCollection 2020 Jan.

  PMID: 31923177 DERIVED

• Siewe Fodjo JN, Mandro M, Mukendi D, Tepage F, Menon S, Nakato S, Nyisi F, Abhafule G, Wonya'rossi D, Anyolito A, Lokonda R, Hotterbeekx A, Colebunders R. Onchocerciasis-associated epilepsy in the Democratic Republic of Congo: Clinical description and relationship with microfilarial density. PLoS Negl Trop Dis. 2019 Jul 17;13(7):e0007300. doi: 10.1371/journal.pntd.0007300. eCollection 2019 Jul.

  PMID: 31314757 DERIVED

• Colebunders R, Mandro M, Mukendi D, Dolo H, Suykerbuyk P, Van Oijen M. 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.

  PMID: 28855148 DERIVED

MeSH Terms

Conditions

Onchocerciasis; Epilepsy

Interventions

Ivermectin

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Michel Mandro, MD

  Chef de Bureau Inspection&Contrôle et Associé de Recherche Clinique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor infectious diseases

Model Details: Randomized clinical trial

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 14, 2017
• Study Start: October 1, 2017
• Primary Completion: December 31, 2017
• Study Completion: August 1, 2018
• Last Updated: January 7, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 10.01.19

Locations

DE (1)