Bridging the Childhood Epilepsy Treatment Gap in Africa

Epilepsy Clinical Trial

— BRIDGE  

Official title:

Bridging the Childhood Epilepsy Treatment Gap in Africa (BRIDGE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04290975
• Other study ID #: 191283
• Secondary ID: PACTR20200386477
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 16, 2020
• Est. completion date: May 31, 2024

Study information

• Verified date: May 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

About half of the world's children with epilepsy do not receive treatment - known as the epilepsy treatment gap - with significantly higher rates (67%-90%) in low- and middle-income countries (LMICs). We will conduct the first cluster-randomized clinical trial (cRCT) to determine the efficacy, implementation, and cost-effectiveness of a novel intervention shifting childhood epilepsy care to epilepsy-trained community health extension workers in an effort to close the epilepsy treatment gap. This research will provide information to help extend epilepsy treatment to children in LMICs and worldwide who suffer from untreated seizures.

Description:

Epilepsy is the most common severe neurological disorder among children. Most children with epilepsy, if treated, can live normal lives. Yet among the world's children living with epilepsy, about 80% of whom reside in low- and middle-income countries (LMICs), about half do not receive treatment; this is described as "the childhood epilepsy treatment gap." Among the LMICs of Africa, the childhood epilepsy treatment gap is about 67%-90% - unchanged for over twenty years. Although the World Health Organization (WHO) and other health agencies recommend that the epilepsy treatment gap be bridged by task shifting epilepsy care to community health extension workers (CHWs) in primary care settings, this recommendation has not been implemented on a large scale. This failure to scale up task shifting in epilepsy care is due to (a) inadequate evidence of efficacy of task-shifted epilepsy care, (b) a lack of methods and tools for implementing epilepsy task shifting, (c) inadequate understanding of task-shifted epilepsy care barriers, and (d) a lack of cost-effectiveness data for health policymakers. CHWs providing task-shifted epilepsy care must identify children with epilepsy, disadvantaged by stigma and unknown to the healthcare system, who are without access to neurologists or electroencephalograms (EEGs). An epilepsy screening tool in the local language (e.g., Hausa) is therefore essential for epilepsy diagnosis, seizure type classification, and medical management. Hausa, the most commonly spoken language in west Africa, with over 120 million Hausa speakers, is used in daily life, commerce, and education; our proposed study will be conducted in three major cities in Hausa-speaking Africa. Funded by an R21 grant (R21TW010899) in preparation for this cluster-randomized clinical trial (cRCT), we developed and piloted in Kano, Nigeria (a) a scalable epilepsy training program for CHWs, (b) an epilepsy community education program in Hausa to facilitate screening, diagnosis and treatment; and (c) an epilepsy data management system. We also (d) validated an epilepsy screening, diagnosis, and seizure classification tool in Hausa, (e) demonstrated feasibility of screening and enrolling children in a cRCT of task-shifted epilepsy care, and (f) piloted a task-shifted epilepsy diagnosis and management protocol. We will now conduct the first cRCT of task-shifted childhood epilepsy care in Africa with the following specific aims: 1. Conduct a non-inferiority cRCT of a task-shifted childhood epilepsy care protocol compared to enhanced usual care (EUC) in three Hausa-speaking cities in northern Nigeria. We will enroll a maximum of 1800 children (age 6 mo, <18 yrs) with epilepsy across 60 randomly selected primary healthcare centers (PHCs) in Kano (30 PHCs), Kaduna (16 PHCs) and Zaria (14 PHCs). PHCs will be randomly assigned to intervention (task-shifted to CHWS childhood epilepsy care; 30 PHCs) or EUC (referral to a physician for epilepsy management; 30 PHCs). Primary outcome: we hypothesize that the proportion of children seizure-free for ≥ 6 months at 24 months follow-up (primary outcome) will be similar in the intervention and EUC arms. Secondary outcomes at 24 months include (a) percent seizure reduction from baseline, (b) time to next seizure after 3 months seizure-free, and (c) accuracy of epilepsy diagnosis and seizure type classification by CHWs compared to assessments by physician epilepsy specialists, blinded to the randomization arm. 2. Assess socio-behavioral and implementation outcomes among providers, parents/guardians and patients in the cRCT. Outcome measures include: (1) Difference in baseline, 12- and 24-month intervention acceptability, appropriateness, and feasibility measures among providers in the task-shifted intervention arm of the cRCT; (2) Difference in baseline, 12- and 24-month quality of life, epilepsy knowledge and stigma, and trust in the healthcare system and providers among participants; (3) Comparison of 12- and 24-month quality of life, knowledge and stigma and trust measures among participants in the intervention and control arms. 3. Determine the cost-effectiveness of the task-shifted epilepsy care intervention. Direct costs of the intervention and EUC will include personnel costs (including CHW epilepsy training) and expenses for diagnostic (EEG, brain imaging) and laboratory tests and anti-epileptic drugs. Indirect costs will include travel time and time away from work for parents/guardians and change in school attendance for patients. Cost-effectiveness will be expressed as US dollars per disability adjusted life year (DALY) averted. This project will also establish a brain disorders clinical research network for Hausa-speaking Africa and provide data for health system leaders and policymakers to scale-up task-shifted childhood epilepsy care.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1800
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 16 Years

Eligibility

Inclusion Criteria:

• Resident of Kano or Kaduna states and living in the Kano, Zaria, or Kaduna metropolitan areas of northern Nigeria
• Parent or guardian provided informed consent for the screening questionnaire given to the parent/guardian
• Parent or guardian informed consent, plus assent for children >7 years able to provide assent, for epilepsy diagnostic evaluation if the screening for possible epilepsy is positive
• Diagnosed with possible epilepsy through initial screening, and then diagnosed with epilepsy upon further evaluation by an epilepsy-trained CHW working with the BRIDGE project, who may consult a BRIDGE physician for diagnostic questions
• Parent or guardian provided consent, and assent for children >7 years able to provide assent, for enrollment in the cRCT of task-shifted epilepsy care versus enhanced physician epilepsy care

Exclusion Criteria:

• Children who have previously been diagnosed with epilepsy and are currently enrolled in other care and treatment, or who have been treated for epilepsy within three months prior to screening
• Children who are currently receiving care by a neurologist or neurosurgeon for a serious brain disorder (e.g., brain tumor, stroke)
• Lack of informed consent, and/or lack of assent from children >7 years who are able to provide assent.Inability of the parent or guardian to communicate with healthcare providers in either Hausa or English
• Any child who screens positive for epilepsy, has epilepsy upon clinical evaluation, but does not live in Kano, Zaria, and Kaduna, and who is in the judgement of the parents and/or BRIDGE staff to be unable to comply with the study visits because of travel distance from home.

Related Conditions & MeSH terms

• Epilepsy

Intervention

Other:
• Task-shifting of follow-up care for pediatric epilepsy
For the intervention arm, follow-up care of children with epilepsy will be shifted to be performed primarily by Community Health Workers (CHWs) with specialized epilepsy training
• Enhanced usual care for pediatric epilepsy
For the intervention arm, follow-up care of children with epilepsy will be performed primarily by physicians, with CHWs serving to collect standardized data regarding outcomes

Locations

Country	Name	City	State
Nigeria	Federal Neuro-Psychiatric Hospital	Kaduna
Nigeria	Aminu Kano Teaching Hospital	Kano
Nigeria	Ahmadu Bello University Teaching Hospital	Zaria

Sponsors (4)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Ahmadu Bello University Teaching Hospital, Aminu Kano Teaching Hospital, Federal Neuro-Psychiatric Hospital, Kaduna

Country where clinical trial is conducted

Nigeria, 

References & Publications (10)

de Boer HM, Moshe SL, Korey SR, Purpura DP. ILAE/IBE/WHO Global Campaign Against Epilepsy: a partnership that works. Curr Opin Neurol. 2013 Apr;26(2):219-25. doi: 10.1097/WCO.0b013e32835f2037. — View Citation

de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008 May;12(4):540-6. doi: 10.1016/j.yebeh.2007.12.019. Epub 2008 Feb 14. — View Citation

Diop AG, de Boer HM, Mandlhate C, Prilipko L, Meinardi H. The global campaign against epilepsy in Africa. Acta Trop. 2003 Jun;87(1):149-59. doi: 10.1016/s0001-706x(03)00038-x. — View Citation

Mbuba CK, Newton CR. Packages of care for epilepsy in low- and middle-income countries. PLoS Med. 2009 Oct;6(10):e1000162. doi: 10.1371/journal.pmed.1000162. Epub 2009 Oct 13. — View Citation

Mbuba CK, Ngugi AK, Fegan G, Ibinda F, Muchohi SN, Nyundo C, Odhiambo R, Edwards T, Odermatt P, Carter JA, Newton CR. Risk factors associated with the epilepsy treatment gap in Kilifi, Kenya: a cross-sectional study. Lancet Neurol. 2012 Aug;11(8):688-96. doi: 10.1016/S1474-4422(12)70155-2. Epub 2012 Jul 6. — View Citation

Mbuba CK, Ngugi AK, Newton CR, Carter JA. The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies. Epilepsia. 2008 Sep;49(9):1491-503. doi: 10.1111/j.1528-1167.2008.01693.x. Epub 2008 Jun 13. — View Citation

Ndoye NF, Sow AD, Diop AG, Sessouma B, Sene-Diouf F, Boissy L, Wone I, Toure K, Ndiaye M, Ndiaye P, de Boer H, Engel J, Mandlhate C, Meinardi H, Prilipko L, Sander JW. Prevalence of epilepsy its treatment gap and knowledge, attitude and practice of its population in sub-urban Senegal an ILAE/IBE/WHO study. Seizure. 2005 Mar;14(2):106-11. doi: 10.1016/j.seizure.2004.11.003. — View Citation

Newton CR, Garcia HH. Epilepsy in poor regions of the world. Lancet. 2012 Sep 29;380(9848):1193-201. doi: 10.1016/S0140-6736(12)61381-6. — View Citation

Wilmshurst JM, Cross JH, Newton C, Kakooza AM, Wammanda RD, Mallewa M, Samia P, Venter A, Hirtz D, Chugani H. Children with epilepsy in Africa: recommendations from the International Child Neurology Association/African Child Neurology Association Workshop. J Child Neurol. 2013 May;28(5):633-44. doi: 10.1177/0883073813482974. Epub 2013 Mar 28. — View Citation

Wilmshurst JM, Kakooza-Mwesige A, Newton CR. The challenges of managing children with epilepsy in Africa. Semin Pediatr Neurol. 2014 Mar;21(1):36-41. doi: 10.1016/j.spen.2014.01.005. Epub 2014 Jan 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost-effectiveness of task-shifted care	Comparison of total financial epilepsy care costs between task-shifted and enhanced usual care study arms, as measured at specified intervals throughout both arms of the study - 1 week, 1 month, 2 months, 4 months, 6 months, 9 months, 12 months, 18 months, and 24 months after enrollment through questions about care received in standardized case report forms, and with financial costs determined by health economists who verify costs of care at specific private and government healthcare facilities.	Data collection over 24 months after enrollment, with analysis of cost-effectiveness data after the final study subject completes the 24-month follow-up visit.
Primary	Percentage seizure-free	Percentage of children in each arm of the study who are seizure-free	Must be seizure-free for 6 or more months at the 24-month visit follow-up visit
Secondary	Reduction in seizure frequency	75% reduction in seizure frequency	Evaluated at 24 months in both arms compared to enrollment (baseline) data
Secondary	Seizure freedom in response to first prescribed anti-epileptic drug	Percentage of children seizure free for 6 months or longer in response to the first anti-epileptic drug prescribed, as measured by questions in standardized case report forms completed by physicians with epilepsy expertise, blinded as to the arm of the study. The blinded physicians will review a daily seizure log which indicates the occurrence and duration of each seizure, maintained by the parent/guardian, to facilitate the blinded physician evaluation.	6 months after enrollment of final subject
Secondary	Diagnostic accuracy	Diagnostic accuracy among study subjects in both arms, determined by blinded physicians	Evaluated by blinded physicians at 1, 6, 12, 18, and 24 months after enrollment
Secondary	Mortality	Differences in mortality between study arms that cannot be explained by potential differences in disease severity	Once, at study conclusion (24 months after enrollment of final subject)
Secondary	Status epilepticus	Difference in frequency of episodes of status epilepticus among children in both arms of the study, as measured by questions in standardized case report forms completed by physicians with expertise in epilepsy, who are blinded as to the arm of the study. The blinded physicians will review a daily seizure log which indicates estimated seizure duration for each seizure, maintained by the parent/guardian, to facilitate the blinded physician evaluation.	Assessed at 1 month, 6 months, 12 months, 18 months and 24 months after enrollment, with analysis of outcome at study conclusion (24 months after enrollment of final subject)
Secondary	Morbidity	Differences in morbidity, including neurodevelopmental morbidity, associated with epilepsy between study arms that emerged during the cRCT	Once, at study conclusion (24 months after enrollment of final subject)
Secondary	Diagnostic tests ordered	Differences by study arm in number and type of diagnostic tests (e.g., MRIs, EEGs) ordered	Once, at study conclusion (24 months after enrollment of final subject)
Secondary	Task-shifted protocol adherence	Percentage adherence by CHWs to protocol in the task-shifted arm	Once, at study conclusion (24 months after enrollment of final subject)
Secondary	Anytime 6-month seizure-free interval	6-month seizure-free intervals as determined by evaluations by physicians with expertise in epilepsy, blinded as to the arm of the study, at 6 months, 12 months, 18 months and 24 months after enrollment. These blinded physicians with expertise in epilepsy will record seizure frequency (including seizure-freedom) on standardized case report forms, facilitated by blinded physician review of daily seizure logs maintained by parents/guardians that will indicate the specific dates and durations of all recorded seizures.	Assessed at 4 time points during 24-month follow-up: 6, 12, 18, and 24 months