Clinical Trial: Treatment of Nodding Syndrome - A Randomized Blinded Placebo-Controlled Crossover Trial of Oral Pyridoxine and Conventional Anti-Epileptic Therapy, in Northern Uganda — 2012

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Treatment of Nodding Syndrome - A Randomized Blinded Placebo-Controlled Crossover Trial of Oral Pyridoxine and Conventional Anti-Epileptic Therapy, in Northern Uganda R

Brief Summary:

Nodding Syndrome (NS) is a novel form of epilepsy seen predominantly among children aged 5-15 years and characterized by head nodding, progressively worsening seizures, and cognitive impairment. To date, the cause of NS remains unclear. A recent assessment by the Uganda Ministry of Health (MOH), World Health Organization (WHO), and US CDC conducted in Kitgum District in northern Uganda documented that the nodding episodes themselves resulted from atonic seizures, and that the children also exhibit multiple different seizure types, both clinically and electrographically. The investigation also found that there was significantly greater sero-positivity for onchocerciasis among children with NS compared with control children, and demonstrated low serum concentrations of vitamin B6 (pyridoxine) among both cases and controls. Vitamin B6 is involved in neurotransmission and has been an effective treatment of seizures for certain rare type of epileptic syndrome. Children with nodding syndrome in Kitgum have been episodically treated with multivitamins, ivermectin, and anti-epileptic medications including phenobarbital, phenytoin, carbamazepine, and valproate, but the possible beneficial or harmful effects of any of these medications for nodding syndrome has not been systematically assessed, and reports from parents and guardians about apparent effectiveness are varied.

The investigators propose a randomized blinded four group clinical trial with crossover design to study the effect and response to therapeutic doses of oral pyridoxine (vitamin B6) and treatment with currently used conventional anti-epileptics including phenytoin and sodium valproate, among children with nodding syndrome.

Detailed Summary:

Nodding Syndrome (NS) is described as an epileptic seizure disorder and has been documented in various geographic areas of sub-Saharan Africa. Jilek et al, 1962, first described several children with attacks of 'nodding head' in Mahenge, a region in southern Tanzania (1,2,3). A missionary doctor described children in southern Sudan in the mid-1990s, where it was first noted in the Lui and Amadi villages of East Mundri county and the Lui region of western Equatoria; a medical NGO then reported the condition to WHO in 1997. An estimated 300 cases were reported in 2003 from this region (4, 5). Winkler et al., using data from Tanzania provided a clinical classification of seizures, semiology and socio-cultural aspects suggesting it was a syndrome (referred to as "head-nodding syndrome") and a form of epilepsy (6, 7). In 2008 and 2009, reports of an illness consistent with NS were reported in Kitgum and Pader districts, northern Uganda. Kaiser et al, in 2009, referred to the phenomenon of head nodding as possibly constituting a feature of an epileptic syndrome caused by O. volvulus (8).

Descriptions of the features of NS appear similar between reports (Appendix A). Nodding is frequently described as occurring in response to some stimulus, frequently being the presence of food or exposure to cold (4, 5, 6, 7). The nodding consists of repetitive bobbing or nodding of the head, sometimes associated with loss of muscle tone in the trunk and upper extremities (6, 7). Consciousness may or may not be impaired during the nodding episodes. The syndrome has been described to be progressive, with gradual neurological deterioration and development of additional seizure types, developmental regression, cognitive decline, and sometimes reportedly resulting in serious injuries or death both due to accidental falls into fires or wells during seizure episodes. Treatment with conventi
Sponsor: Centers for Disease Control and Prevention

Current Primary Outcome: Change in the frequency of observed head nodding and other seizure activity from baseline (which is the frequency at week 1) [ Time Frame: 1 week, 5 weeks, 7 weeks, 12 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Centers for Disease Control and Prevention

Dates:
Date Received: November 9, 2012
Date Started: February 2013
Date Completion: September 2013
Last Updated: November 20, 2012
Last Verified: November 2012