Journal article
Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.
- Abstract:
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Background Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O. volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O. volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment.
Methods This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100 mg daily for six weeks in 230 participants. Participants will be patients’ ages≥8 years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1–2 weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries) 100 mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6 weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24 months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life.
Discussion This trial postulates that targeting O. volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome.
Trial registration Registered with clinicaltrials.gov ID: NCT02850913 on 1st August, 2016.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1022.5KB, Terms of use)
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- Publisher copy:
- 10.1186/s12883-019-1256-z
Authors
- Publisher:
- BioMed Central
- Journal:
- BMC Neurology More from this journal
- Volume:
- 19
- Issue:
- 1
- Article number:
- 35
- Publication date:
- 2019-03-06
- Acceptance date:
- 2019-02-13
- DOI:
- ISSN:
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1471-2377
- Pmid:
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30841858
- Language:
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English
- Keywords:
- Pubs id:
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pubs:980897
- UUID:
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uuid:1ff0d595-ddc7-47c4-9870-f722123af48e
- Local pid:
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pubs:980897
- Source identifiers:
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980897
- Deposit date:
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2019-03-23
Terms of use
- Copyright holder:
- Idro et al
- Copyright date:
- 2019
- Notes:
- © The Author(s). 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Licence:
- CC Attribution (CC BY)
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