Clinical Trial: Doxycycline for the Treatment of Nodding Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Doxycycline for the Treatment of Nodding Syndrome: A Phase II, Randomised Placebo Controlled Trial

Brief Summary: Nodding syndrome (NS) is a devastating neurologic disorder affecting thousands of children in Africa. A number of toxic, nutritional, infectious, para-infectious and environmental causes have been studied but the only consistent association has been with infection by the parasite Onchocerca volvulus. There is no specific treatment for NS and also for the adult onchocerca. However, antibiotic depletion of the Onchocerca volvulus co-symbiotic bacteria Wolbachia with tetracyclines such as doxycycline results in sterilisation and premature death of the adult worm and marked reductions in dermal microfilaria density. Potentially, such therapy that kills adult onchocerca volvulus may improve the outcome of NS if the association were true.

Detailed Summary:

Primary hypothesis

Oral doxycycline 100mg daily for six weeks in patients with NS aged 8 years or older will reduce inflammatory responses and the proportion of patients with serum antibodies to NSPs or leiomodin 24 months after intervention by 40% compared to placebo.

Primary efficacy objective

To determine the effects of doxycycline 100mg daily for six weeks in patients with NS 8 years or older on serum levels of antibodies to NSPs (VGKC complex and others to be identified in a concurrent case-control study) or leiomodin at 24 months.

Study Type

This will be a two-arm, placebo-controlled (double blind) randomized phase II trial of oral doxycycline 100mg daily for six weeks.

Study site

Kitgum general hospital, Kitgum, Uganda.

Study Population

Study participants will be patients with confirmed NS as defined according to the World Health Organization (WHO) consensus case definition i.e. (i) Head nodding on two or more occasions, (ii) Occurring in clusters at a frequency of 5-20/minute, (iii) Onset between the ages of 3-18 years, (iv) Observed by a trained health worker or documented on EEG

Plus any one of:

a) triggered by food or cold weather; b) presence of other seizures or neurological abnormalities and cognitive decline and c) clustering in space or time), age ≥8 years, and with written consent from a parent or guardian.

St
Sponsor: Makerere University

Current Primary Outcome: Proportion of patients with antibodies to Neuron Surface Proteins (NSPs) or leiomodin at 24 months. [ Time Frame: 24 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean change in serum concentrations of antibodies to NSPs or leiomodin [ Time Frame: From baseline (time 0 months) to 24 months ]
  • Mean change in serum concentrations of C-Reactive Protein [ Time Frame: From baseline (time 0 months) to 24 months ]
  • Mean change in serum concentrations of C3a and C3b [ Time Frame: From baseline (time 0 months) to 24 months ]
  • Mean change in dermal microfilaria density on real time Polymerase Chain Reaction at 24 months [ Time Frame: From baseline (time 0 months) to 24 months ]
  • The proportions of patients achieving seizure freedom (≥1 month without head nodding or convulsive seizures) [ Time Frame: 24 months ]
  • Proportion of patients with interictal epileptiform discharges on 30-minute diagnostic EEG [ Time Frame: 24 months ]
  • Proportion of participants with Gross Motor Function Classification System (GMFCS) scores 3-5 [ Time Frame: 24 months ]
  • Proportion of participants with mental health disorders on the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) [ Time Frame: 24 months ]
  • Mean change in cogstate scores [ Time Frame: From baseline (time 0 months) to 24 months ]
  • Proportion of participants with improved Quality of Life (a perception) on the Quality of Life in Childhood Epilepsy Questionnaire [ Time Frame: From baseline (time 0 months) to 24 months ]
  • Incidence rate of non-nodding syndrome sick clinic visits and all cause sick clinic visits [ Time Frame: 24 months ]
  • The proportion of participants with stunting (height for age Z-scores <-3 SD) [ Time Frame: 24 months ]
  • The proportion of participants with wasting (weight for height Z-scores <-3 SD) [ Time Frame: 24 months ]
  • All-cause mortality [ Time Frame: 24 months ]
  • Incidence rate of all-cause hospital admissions [ Time Frame: 24 months ]


Original Secondary Outcome: Same as current

Information By: Makerere University

Dates:
Date Received: March 9, 2016
Date Started: September 5, 2016
Date Completion: August 5, 2020
Last Updated: February 22, 2017
Last Verified: February 2017