- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02850913
Doxycycline for the Treatment of Nodding Syndrome
Doxycycline for the Treatment of Nodding Syndrome: A Phase II, Randomised Placebo Controlled Trial
Study Overview
Detailed Description
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.
Study Interventions
Participants will receive standard of care supportive treatment according to current guidelines for NS (antiepileptic drug treatment with sodium valproate, management of psychiatric disorders, nutritional, physical and occupational therapy as indicated).
All will be hospitalised in the first weeks during which period, baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised.
Sample size: The sample size (115 participants per arm i.e. 230 total) is estimated based on the assumption that a six-weeks treatment course of doxycycline will reduce the proportion of participants with antibodies to NSPs or Leiomodin by 40% (from 50.0% to 30.0%) 24 months after initiation of the intervention while providing for 10% loss to follow-up (β=80%, α=0.05).
Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries, Ltd) 100mg daily for six weeks or identical placebo. Treatment will be initiated in hospital but will be continued at home. Each participant will be visited at home at 2, 4 and 6 weeks for adherence monitoring and assessment of safety and will report back to the hospital study clinic at 6, 12 and 24 months.
Follow-up procedures:
Participants will be followed up at 2, 4, and 6 weeks by the health visitor to document adherence and assess safety and will be assessed for outcomes in hospital at 24 months after initiation of the intervention.
Data Analysis:
Primary analysis will be by intention to treat. The investigators will examine the effect of doxycycline at 24 months on antibodies to host NSPs and leiomodin, inflammatory responses (CRP, C3a and C3b), on epileptiform discharges and seizure control, and microfilaria density/ Wolbachia load, and on clinical (cognitive, motor, psychiatric and quality of life) symptoms compared to placebo.
In a sub-analysis, the investigators will examine the effects of the intervention in new patients compared to patients with long standing symptoms.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Richard Idro, MMed, PhD
- Phone Number: +256774274173
- Email: ridro1@gmail.com
Study Locations
-
-
-
Kampala, Uganda, +256
- Recruiting
- Makerere University College of Health Sciences
-
Contact:
- Richard Idro, MMed, PhD
- Phone Number: +256774274173
- Email: ridro1@gmail.com
-
Contact:
- Ronald Anguzu, MBChB, MPH
- Phone Number: +256702919292
- Email: ranguzu@musph.ac.ug
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Participants with confirmed NS as defined by the WHO i.e. Head nodding on two or more occasions (both past and current)
- Symptom onset between the ages of 3-18 years
- Observed by a trained health worker or documented on EEG
Plus any one of:
- Triggered by food or cold weather
- Presence of other seizures or neurological abnormalities and cognitive decline
- Clustering in space or time.
- Age 8 years or older
- Written consent by the parent or guardian
Exclusion Criteria:
- Females with a positive urinary HCG (pregnancy) test
- Patients receiving Phenobarbitone, Carbamazepine, Phenytoin or Rifampicin.
- Known hypersensitivity to study drug
- Withdrawal of consent since enrollment
- Reported inability to swallow capsules
- Enrolled or known agreement to enroll into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study
- Suspected high likelihood of non-compliance with study drug and the follow-up schedule - e.g. dependent on a carer who is unlikely to consistently be available.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Doxycycline
|
Other Names:
|
Placebo Comparator: Placebo
|
- Placebo (matching capsules containing no active ingredients)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients with antibodies to Neuron Surface Proteins (NSPs) or leiomodin at 24 months.
Time Frame: 24 months
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
All-cause mortality
Time Frame: 24 months
|
24 months
|
Mean change in serum concentrations of antibodies to NSPs or leiomodin
Time Frame: From baseline (time 0 months) to 24 months
|
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
|
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
|
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
|
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
|
24 months
|
Proportion of patients with interictal epileptiform discharges on 30-minute diagnostic EEG
Time Frame: 24 months
|
24 months
|
Proportion of participants with Gross Motor Function Classification System (GMFCS) scores 3-5
Time Frame: 24 months
|
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
|
24 months
|
Mean change in cogstate scores
Time Frame: From baseline (time 0 months) to 24 months
|
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
|
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
|
24 months
|
The proportion of participants with stunting (height for age Z-scores <-3 SD)
Time Frame: 24 months
|
24 months
|
The proportion of participants with wasting (weight for height Z-scores <-3 SD)
Time Frame: 24 months
|
24 months
|
Incidence rate of all-cause hospital admissions
Time Frame: 24 months
|
24 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Richard Idro, MMED, PhD, Makerere University College of Health Sciences
- Principal Investigator: Kevin Marsh, MRCP, DTM&H, University of Oxford
Publications and helpful links
General Publications
- Idro R, Anguzu R, Ogwang R, Akun P, Abbo C, Mwaka AD, Opar B, Nakamya P, Taylor M, Elliott A, Vincent A, Newton C, Marsh K. Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial. BMC Neurol. 2019 Mar 6;19(1):35. doi: 10.1186/s12883-019-1256-z.
- Anguzu R, Akun PR, Ogwang R, Shour AR, Sekibira R, Ningwa A, Nakamya P, Abbo C, Mwaka AD, Opar B, Idro R. Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial - challenges, enablers and lessons learned. Glob Health Action. 2018;11(1):1431362. doi: 10.1080/16549716.2018.1431362.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-022
- 12-16 (Other Identifier: Oxford Tropical Research Ethics Committee (OxTREC))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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