Faculty Collaboration Database

Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial. BMC Neurol 2019 Mar 06;19(1):35

Date

03/08/2019

Pubmed ID

30841858

Pubmed Central ID

PMC6402111

DOI

10.1186/s12883-019-1256-z

Scopus ID

2-s2.0-85062585181 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

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.

Author List

Idro R, Anguzu R, Ogwang R, Akun P, Abbo C, Mwaka AD, Opar B, Nakamya P, Taylor M, Elliott A, Vincent A, Newton C, Marsh K

Author

Ronald Anguzu MD, PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antiparasitic Agents
Child
Double-Blind Method
Doxycycline
Humans
Male
Nodding Syndrome
Onchocerca volvulus
Quality of Life
Research Design
Treatment Outcome
Uganda