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

NCT01730313 | Withdrawn Phase 2 DMC

• 1 other identifier: CDC-CGH-6318
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Nodding Syndrome

Keywords

Nodding syndrome

Outcome Measures

Primary Outcomes (1)

• Change in the frequency of observed head nodding and other seizure activity from baseline (which is the frequency at week 1)

  Change (Reduction) in frequency of observed head nodding or other seizure activity episodes among children with NS

  1 week, 5 weeks, 7 weeks, 12 weeks

Study Arms (4)

Pyridoxine (B6)

EXPERIMENTAL

Oral pyridoxine, 30- 50 mg/kg/day in one daily dose (powder form)for a period of four weeks followed by cross-over to Phenytoin arm for another four weeks

Drug: Pyridoxine; Drug: Phenytoin

Phenytoin

EXPERIMENTAL

Phenytoin Oral, 5 mg/kg/day in two equally divided doses(powder form)for a period of four weeks and then cross-over to Pyridoxine arm for another four weeks

Drug: Pyridoxine; Drug: Phenytoin

Sodium Valproate

EXPERIMENTAL

Sodium valproate oral, 10 - 15 mg/kg/day once daily powder form)for a period of four weeks and then cross-over to placebo arm for another four weeks

Drug: Sodium Valproate; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo will consist of an inert substance (e.g., gelatin) with an appearance similar to medication in similar dosage as the study arms for a period of 4 weeks and subsequent cross-over to Sodium Valproate arm

Drug: Sodium Valproate; Drug: Placebo

Interventions

Pyridoxine DRUG

Also known as: Vitamin B6

Phenytoin; Pyridoxine (B6)

Sodium Valproate DRUG

Placebo; Sodium Valproate

Phenytoin DRUG

Phenytoin; Pyridoxine (B6)

Placebo DRUG

Placebo; Sodium Valproate

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Plan to remain in the study area/region for at least two months from the time of entry
• Are attended by a care giver who is/are able to understand and give informed consent
• Are at least 5 years old at the time of entry into the study and not more than 17 years

You may not qualify if:

• Have a history of allergic reaction to any anti-epileptic medications
• Have severe acute malnutrition diagnosed based on anthropometric measurements
• Have known or suspected condition in which anti-epileptic medications or pyridoxine treatment is contraindicated

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Ministry of Health, Uganda: collaborator

Study Sites (1)

Kitgum Nodding Syndrome Treatment Center, Kitgum General Hospital

Kitgum, Uganda

Location

MeSH Terms

Conditions

Nodding Syndrome

Interventions

Pyridoxine; Vitamin B 6; Valproic Acid; Phenytoin

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Hydantoins; Imidazolidines; Imidazoles; Azoles

Study Officials

• Scott Dowell, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• JAMES SEJVAR, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• SUDHIR BUNGA, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• RICHARD IDRO, MD

  Ministry of Health, Uganda

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2012
• First Posted: November 21, 2012
• Study Start: February 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

UG (1)