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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by Centers for Disease Control and Prevention
Sponsor:
Collaborator:
Ministry of Health, Uganda
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01730313
First received: November 9, 2012
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Nodding Syndrome
Drug: Pyridoxine
Drug: Sodium Valproate
Drug: Phenytoin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Nodding Syndrome - A Randomized Blinded Placebo-Controlled Crossover Trial of Oral Pyridoxine and Conventional Anti-Epileptic Therapy, in Northern Uganda — 2012

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Change (Reduction) in frequency of observed head nodding or other seizure activity episodes among children with NS


Estimated Enrollment: 80
Study Start Date: February 2013
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pyridoxine (B6)
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
Other Name: Vitamin B6
Drug: Phenytoin
Experimental: Phenytoin
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
Other Name: Vitamin B6
Drug: Phenytoin
Experimental: Sodium Valproate
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 Comparator: Placebo
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730313

Contacts
Contact: Sudhir Bunga, MD 678-314-1380 sbunga@cdc.gov
Contact: James Sejvar, MD 404-536-4203 zea3@cdc.gov

Locations
Uganda
Kitgum Nodding Syndrome Treatment Center, Kitgum General Hospital Not yet recruiting
Kitgum, Uganda
Contact: RICHARD IDRO, MD    +256-774274173    ridro1@gmail.com   
Contact: SUDHIR BUNGA, MD    678-314-1380    sbunga@cdc.gov   
Principal Investigator: SUDHIR BUNGA, MD         
Principal Investigator: RICHARD IDRO, MD         
Sponsors and Collaborators
Ministry of Health, Uganda
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01730313     History of Changes
Other Study ID Numbers: CDC-CGH-6318
Study First Received: November 9, 2012
Last Updated: November 20, 2012
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
Nodding syndrome

Additional relevant MeSH terms:
Nodding Syndrome
Syndrome
Brain Diseases
Central Nervous System Diseases
Disease
Epilepsy
Epilepsy, Generalized
Nervous System Diseases
Pathologic Processes
Anticonvulsants
Phenytoin
Pyridoxal
Pyridoxine
Valproic Acid
Vitamin B 6
Antimanic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Growth Substances
Membrane Transport Modulators
Micronutrients
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 23, 2014