ClinicalTrials.gg
CompletedNCT06811129Updated Oct 29, 2026

Long-Term Neurologic and Neurocognitive Sequelae Following Pediatric Ebola Virus in Liberia

An observational study in Ebola and Post-Acute Ebola Syndrome, sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Completed at 1 site in Liberia. Open to participants aged 7 Years to 30 Years. Per ClinicalTrials.gov, last updated 2026-10-29.

Sponsored by National Institute of Neurological Disorders and Stroke (NINDS) · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
328
Ages
7 Years to 30 Years
Sex
All
01

Study summary

Background:

Ebola virus disease (EVD) causes fever, vomiting, and diarrhea, and may cause internal bleeding. It is often fatal. EVD may also damage the brain and nervous system. It can cause headaches, tremors, weakness, and other problems. These issues can continue for years after people recover from EVD infection. Researchers want to understand more about how EVD may have affected the brains of people who contracted the disease as children.

Objective:

To learn more about the long-term effects of EVD on the brain and nervous system in people who had the disease as children.

Eligibility:

People who were less than 18 years old when they took part in a previous study called the PREVAIL III Natural History of Ebola study. They can be either a survivor of EVD or a close contact. A close contact is someone who had a relationship with a person who survived EVD but never had the disease themself.

Design:

Participants will have 1 clinic visit. They will undergo several tasks:

They will have an exam of their nervous system performed by a neurologist. They will do physical tasks and answer questions about any problems or symptoms since they had EVD.

They may have blood drawn.

They will have tests of their memory, attention, and thinking skills. For one test, participants will answer questions and solve puzzles using pencil and paper. For another test, they will play 4 different games on an iPad.

They will have an interview. A researcher will ask questions about their mood and other symptoms that may affect their brain and nervous system; their past medical diagnoses, symptoms, and experiences; and how they are doing at home, school, or work.

Read the detailed description

Study Description:

The long-term neurological sequelae of Ebola virus disease (EVD) are not well-described, particularly in survivors infected during pediatric age. The 2015 west Africa EVD epidemic had dramatic effect on adults and children and by one year following infection, concerns for neurologic sequelae became apparent. The PREVAIL III (PIII) Ebola Natural History Study in Monrovia, Liberia had a number of substudies, including both an adult Neurology and pediatric Neurology Substudy which were undertaken to better understand the long-term neurologic sequelae of EVD. The adult Neurology Substudy had over five years of follow up visits whereas the original Pediatric Neurology Substudy cohort was composed of a small sample of children seen in 2015 one time under PIII with no subsequent follow ups. Although this pediatric cohort was small, pilot data from this assessment revealed lower cognitive scores in the pediatric EVD survivors compared to controls, as well as worse executive function scores, more complaints of neuropsychiatric symptoms, and worse disability on modified Rankin Scale, among other findings. PIII subsequently closed out between 2020 and 2021. Here we propose a new protocol to observe and study the neurologic and neurocognitive sequelae following Ebola virus exposure at an age below 18. We propose conducting a single in-person neurologic visit including neurologic exam, neurocognitive assessment, and neurologic history and symptom questionnaire to be given to participants at greater than 5-years following exposure. We also plan to do a single blood draw at time of visit to assess for Ebola Virus antibody titers in survivors and close contacts (controls). The participants included in this study will include Ebola survivors and close contacts (controls) that were enrolled in PIII at age less than 18. We hypothesize that some pediatric Ebola survivors will have longterm neurologic sequelae at greater than 5 years post exposure that may be subtle in nature. Included in this study will be one embedded substudy.

Longitudinal Pediatric Neuro EVD Substudy: We propose to see the original small cohort of pediatric participants seen in 2015 for a second visit as a longitudinal sub study. In evaluating our longitudinal cohort, we expect that some of the sequelae noted during their initial evaluation may have improved over time, but these survivors still may have persistent neurological sequelae even after over 5 years convalescence from EVD.

Objectives:

Primary Objective:

  1. Pediatric EVD Neuro Follow up Study: To observe and describe the range of neurologic and neurocognitive findings that are present in EVD survivors at greater than 5 years following infection as compared to controls.
  2. Longitudinal Pediatric Neuro EVD Substudy (Subset of population): To compare neurologic and neurocognitive findings found in EVD survivors and controls at greater than 5 years following infection to that of the same participants at first visit about 1 year post infection.

Secondary Objectives

  1. Pediatric EVD Neuro Follow up Study: To characterize serum Zaire Ebola virus (EBOV) specific antibodies in pediatric EVD survivors at greater than 5 years following infection compared to that of controls.
  2. Longitudinal Pediatric Neuro EVD Substudy: To characterize serum EBOV specific antibodies in pediatric EVD survivors at greater than 5 years following infection to that of the same participant at first visit about 1 year post infection.

Exploratory Objective:

Pediatric EVD Neuro Follow up Study

  1. To compare EBOV specific antibodies in pediatric EVD survivors with and without neurologic and neurocognitive sequelae.
  2. To compare neurologic and neurocognitive findings in pediatric EVD survivors and controls at greater than 5 years post infection to that of adult participants from the PIII adult Neurology sub study.
  3. To explore the presence of other serologic markers in pediatric EVD survivors compared to close-contacts (control).

Outcomes:

Primary Endpoint:

  1. Pediatric EVD Neuro Follow up Study: In comparison of EVD survivors at greater than 5 years following infection with close contacts (controls), the prevalence of:

    • neurological symptoms (as asked on neurologic symptom questionnaire CRF)
    • physical disability (as assessed through MRS score)
    • executive function dysfunction (as assessed through executive function assessment questions)
    • neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF)
    • neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit)
    • neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam and ICA-P assessment)
  2. Longitudinal Pediatric Neuro EVD Substudy: In comparison of EVD survivors at greater than 5 years following infection to that at first visit about 1 year after infection, the change in:

    • number of neurological symptoms (as asked on neurologic symptom questionnaire CRF)
    • Physical disability (as assessed through MRS score)
    • Executive function dysfunction (as assessed through executive function assessment questions).
    • number of neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF.
    • persistence of neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit).
    • neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam and ICA-P assessment).

Secondary Endpoints:

  1. Pediatric EVD Neuro Follow up Study: The degree of antibody response in pediatric EVD survivors at greater than 5 years following infection compared to that of close contacts (controls).
  2. Longitudinal Pediatric Neuro EVD Substudy: The degree of antibody response in pediatric EVD survivors at greater than 5 years following infection compared to that at about 1 year following infection.

Exploratory Endpoints:

Pediatric EVD Neuro Follow up Study:

  1. In EVD survivors at greater than 5 years post infection, the correlation between serum EBOV specific antibody presence and:

    • presence of neurological symptoms (as asked on neurologic symptom questionnaire CRF).
    • presence of physical disability (as assessed through MRS score).
    • presence of executive function dysfunction (as assessed through executive function assessment questions)
    • presence of neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF)
    • presence of neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit).
    • presence of neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam)
  2. In pediatric versus adult EVD survivors at greater than 5 years following infection, the prevalence of:

    • neurological symptoms (as asked on neurologic symptom questionnaire CRF).
    • physical disability (as assessed through MRS score)
    • neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF)
    • neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit)
    • neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam).
  3. The profile of serologic immune markers in pediatric EVD survivors at greater than 5 years following infection.
02

Conditions studied

  • Ebola
  • Post-Acute Ebola Syndrome

Keywords

  • Ebola
  • Neurologic
  • Pediatric
  • Post-Acute Ebola Syndrome
  • Cognitive
  • Global Neurology
03

In context

Hemorrhagic Fever, Ebola

104 studies on the registry are indexed under Hemorrhagic Fever, Ebola; 13 are open to participants now.

This study's enrollment of 328 is above the median of 266 across 16 observational studies indexed under Hemorrhagic Fever, Ebola.

Browse Hemorrhagic Fever, Ebola studies →

Lead sponsor

National Institute of Neurological Disorders and Stroke (NINDS) is the lead sponsor of 601 studies on the registry; 56 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 8 (44%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
7 Years to 30 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

This study will include participants of the PREVAIL III Natural History of Ebola Study who were of pediatric age at the time of enrollment, including EVD survivors and close contacts.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Stated willingness to comply with all study procedures and availability for the duration of the study.
  2. Male or female, previously enrolled in PREVAIL III Natural History of Ebola study as either an EVD survivor, or a close contact.*
  3. Aged \< 18 Years Old at the time of enrollment in PREVAIL III Natural History of Ebola study.
  4. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written document.

    • Close contacts are those who had a relationship with someone who survived EVD but were never diagnosed with EVD themselves.

Exclusion criteria

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. At the time of enrollment, lacks consent capacity due to cognitive impairment that would make them incapable of understanding the explanation of the procedures in this study. Cognitive capacity to consent will be determined at the time of enrollment. Participants with mental disorders or those participants who are cognitively impaired yet still retain consent capacity will not be excluded.
  2. Is unable to comply with the procedures of the protocol.
  3. Has any condition in the judgement of the study staff that would make the volunteer unable to participate in the study.
  4. Is non-English speaking.

Justification for the Exclusion of Non-English Speakers

We plan to include speakers of simple Liberian English in this study. The tools we use for cognitive testing are not validated in any other language, other than English. It is expected that most, if not all, of the cohort we will be recruiting from will be simple Liberian English speakers.

Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
328 participants (actual)

Groups and cohorts

  • Close Contacts

    Male of female, previously enrolled in PREVAIL III Natural History of Ebola study as a close contact. Close contacts are those who had a relationship with someone who survived EVD but were never diagnosed with EVD themselves.

  • EVD Survivors

    Male or female, previously enrolled in PREVAIL III Natural History of Ebola study as an EVD survivor.

06

What researchers measure

Primary outcomes

  1. Pediatric EVD Neuro Follow up Study

    To observe and describe the range of neurologic and neurocognitive findings that are present in EVD survivors at greater than 5 years following infection as compared to controls. In comparison of EVD survivors at greater than 5 years following infection with close contacts, the prevalence of:- neurological symptoms (as asked on neurologic symptom questionnaire CRF) - physical disability (as assessed through MRS score) - executive function dysfunction (as assessed through executive function assessment questions) - neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF) - neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit) - neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam and ICA-P assessment)

    Time frame: 5-10 years post-infection

  2. Longitudinal Pediatric Neuro EVD Sub study (Subset of population)

    To compare neurologic and neurocognitive findings found in EVD survivors and controls at greater than 5 years following infection to that of the same participants at first visit about 1 year post infection.- number of neurological symptoms (as asked on neurologic symptom questionnaire CRF) - Physical disability (as assessed through MRS score) - Executive function dysfunction (as assessed through executive function assessment questions).- number of neuropsychiatric symptoms (as indicated on neuropsychiatric symptom portion of CRF.- persistence of neurologic exam abnormalities (as found on full neurologic physical exam performed by licensed neurologist during visit).- neurocognitive deficits (as determined by cognitive exam scores on NIH Toolbox exam and ICA-P assessment).

    Time frame: 5-10 years post-infection

Secondary outcomes

  1. Longitudinal Pediatric Neuro EVD Sub study:

    The degree of antibody response in pediatric EVD survivors after 5 years or more of convalescence from EVD compared to that at 1 year following infection.

    Time frame: 5-10 years post-infection

  2. Pediatric EVD Neuro Follow up Study

    The degree of antibody response in pediatric EVD survivors after 5 years or more of convalescence from EVD compared to that of controls.

    Time frame: 5-10 years post-infection

07

Study locations

1 site
  • John F. Kennedy Medical Center
    Monrovia, Liberia
08

References and documents

Publications

  • Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwiki KR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E, Van den Enden E. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999 Feb;179 Suppl 1:S1-7. doi: 10.1086/514308. PubMed 9988155 ↗
  • Clark DV, Kibuuka H, Millard M, Wakabi S, Lukwago L, Taylor A, Eller MA, Eller LA, Michael NL, Honko AN, Olinger GG Jr, Schoepp RJ, Hepburn MJ, Hensley LE, Robb ML. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis. 2015 Aug;15(8):905-12. doi: 10.1016/S1473-3099(15)70152-0. Epub 2015 Apr 21. PubMed 25910637 ↗
  • Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK, Colubri A, Sealfon RS, Kanneh L, Moigboi A, Momoh M, Fullah M, Moses LM, Brown BL, Andersen KG, Winnicki S, Schaffner SF, Park DJ, Yozwiak NL, Jiang PP, Kargbo D, Jalloh S, Fonnie M, Sinnah V, French I, Kovoma A, Kamara FK, Tucker V, Konuwa E, Sellu J, Mustapha I, Foday M, Yillah M, Kanneh F, Saffa S, Massally JL, Boisen ML, Branco LM, Vandi MA, Grant DS, Happi C, Gevao SM, Fletcher TE, Fowler RA, Bausch DG, Sabeti PC, Khan SH, Garry RF; KGH Lassa Fever Program; Viral Hemorrhagic Fever Consortium; WHO Clinical Response Team. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014 Nov 27;371(22):2092-100. doi: 10.1056/NEJMoa1411680. Epub 2014 Oct 29. PubMed 25353969 ↗
  • Chertow DS, Nath A, Suffredini AF, Danner RL, Reich DS, Bishop RJ, Childs RW, Arai AE, Palmore TN, Lane HC, Fauci AS, Davey RT. Severe Meningoencephalitis in a Case of Ebola Virus Disease: A Case Report. Ann Intern Med. 2016 Aug 16;165(4):301-4. doi: 10.7326/M15-3066. Epub 2016 Apr 5. No abstract available. PubMed 27043004 ↗
  • Howlett P, Brown C, Helderman T, Brooks T, Lisk D, Deen G, Solbrig M, Lado M. Ebola Virus Disease Complicated by Late-Onset Encephalitis and Polyarthritis, Sierra Leone. Emerg Infect Dis. 2016 Jan;22(1):150-2. doi: 10.3201/eid2201.151212. No abstract available. PubMed 26690042 ↗
  • Jacobs M, Rodger A, Bell DJ, Bhagani S, Cropley I, Filipe A, Gifford RJ, Hopkins S, Hughes J, Jabeen F, Johannessen I, Karageorgopoulos D, Lackenby A, Lester R, Liu RS, MacConnachie A, Mahungu T, Martin D, Marshall N, Mepham S, Orton R, Palmarini M, Patel M, Perry C, Peters SE, Porter D, Ritchie D, Ritchie ND, Seaton RA, Sreenu VB, Templeton K, Warren S, Wilkie GS, Zambon M, Gopal R, Thomson EC. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet. 2016 Jul 30;388(10043):498-503. doi: 10.1016/S0140-6736(16)30386-5. Epub 2016 May 18. PubMed 27209148 ↗
  • Fallah MP, Reilly C, Van Ryn C, Badio M, Camanor SW, Kaler SG, Johnson B, Orone R, Flumo H, Moses SJ, Johnson KL, Gorpudolo N, Gayedyu-Dennis D, Dighero-Kemp B, Fayiah J, Marron L, Hensley LE, Taylor RJ, Higgs ES, Lane HC, Neaton JD, Sneller MC. Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study. Lancet Glob Health. 2023 Jul;11(7):e1053-e1060. doi: 10.1016/S2214-109X(23)00210-3. PubMed 37349033 ↗
  • Foeller ME, Carvalho Ribeiro do Valle C, Foeller TM, Oladapo OT, Roos E, Thorson AE. Pregnancy and breastfeeding in the context of Ebola: a systematic review. Lancet Infect Dis. 2020 Jul;20(7):e149-e158. doi: 10.1016/S1473-3099(20)30194-8. Epub 2020 May 6. PubMed 32595045 ↗
  • PREVAIL III Study Group; Sneller MC, Reilly C, Badio M, Bishop RJ, Eghrari AO, Moses SJ, Johnson KL, Gayedyu-Dennis D, Hensley LE, Higgs ES, Nath A, Tuznik K, Varughese J, Jensen KS, Dighero-Kemp B, Neaton JD, Lane HC, Fallah MP. A Longitudinal Study of Ebola Sequelae in Liberia. N Engl J Med. 2019 Mar 7;380(10):924-934. doi: 10.1056/NEJMoa1805435. PubMed 30855742 ↗
  • Diallo MSK, Ayouba A, Keita AK, Thaurignac G, Sow MS, Kpamou C, Barry TA, Msellati P, Etard JF, Peeters M, Ecochard R, Delaporte E, Toure A; PostEbogui Study Group. Temporal evolution of the humoral antibody response after Ebola virus disease in Guinea: a 60-month observational prospective cohort study. Lancet Microbe. 2021 Dec;2(12):e676-e684. doi: 10.1016/S2666-5247(21)00170-1. Epub 2021 Sep 3. PubMed 35544108 ↗

Individual participant data

Plan to share: No

09

Timeline

4 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Feb 2025 to primary completion in Sep 2025, 6 months.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 5, 2025
First posted
Feb 6, 2025
StartActual
Feb 14, 2025
Primary completionActual
Sep 9, 2025
CompletionActual
Sep 9, 2025
Last update
Oct 29, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Minor edits
Nothing that changes what the study is or who can join. Edited: description
4 updates, last Oct 29, 2026
Show all 4 updates
  1. Oct 29, 2026
    Minor edits only
    + 1 other change: description
  2. Oct 16, 2026
    Minor edits only
    + 1 other change: description
  3. Oct 2, 2026
    Minor edits only
    + 1 other change: description
  4. Sep 28, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06811129
Responsible party
Sponsor
First posted
Feb 6, 2025
Start date
Feb 14, 2025
Primary completion
Sep 9, 2025
Completion
Sep 9, 2025
Last update
Oct 29, 2026

Study contacts

Bridgette J Billioux, M.D.
principal investigator · National Institute of Neurological Disorders and Stroke (NINDS)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

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