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

• Status: Unknown status
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centers for Disease Control and Prevention
• Collaborator: Ministry of Health, Uganda
• Treatments: Anticonvulsants; Phenytoin; Pyridoxal; Pyridoxine; Valproic Acid; Vitamin B 6

Criteria

Inclusion Criteria: All children identified at clinic level and/or community level in the study region will be eligible to enter into the study if they meet the following inclusion criteria after completing the screening form (Appendix H):

1. Clinical head nodding episodes with or without other types of seizure activity with a frequency of at least 1 per day (7 episodes per week). [The seizures must be frequent enough so that a change/decrease in that frequency is measurable.] Children will be stratified into those with high frequency or observed nodding (with 3 or more episodes daily), and lower frequency events (more than one but fewer than 3 episodes per day reported).

2. Plan to remain in the study area/region for at least two months from the time of entry

3. Are attended by a care giver who is/are able to understand and give informed consent

4. Are at least 5 years old at the time of entry into the study and not more than 17 years

Exclusion Criteria: Children will not be eligible for registration (or will be excluded from the trial if already registered) if they are determined to meet any of the following exclusion criteria when screened initially or at the time of entry into study:

1. Have a history of allergic reaction to any anti-epileptic medications

2. Have severe acute malnutrition diagnosed based on anthropometric measurements

3. Have known or suspected condition in which anti-epileptic medications or pyridoxine treatment is contraindicated

4. Because both phenytoin and valproate have been associated with birth defects and adverse events on the developing fetus, pregnancy will be ruled out before inclusion of females reaching menarche. Pregnant females will not be included in the study.