NCT02850913

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
230

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 9, 2016

Completed
5 months until next milestone

First Posted

Study publicly available on registry

August 1, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

September 5, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 5, 2020

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 5, 2020

Completed
Last Updated

February 23, 2017

Status Verified

February 1, 2017

Enrollment Period

3.6 years

First QC Date

March 9, 2016

Last Update Submit

February 22, 2017

Conditions

Seizures

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients with antibodies to Neuron Surface Proteins (NSPs) or leiomodin at 24 months.

    24 months

Secondary Outcomes (15)

  • Mean change in serum concentrations of antibodies to NSPs or leiomodin

    From baseline (time 0 months) to 24 months

  • Mean change in serum concentrations of C-Reactive Protein

    From baseline (time 0 months) to 24 months

  • Mean change in serum concentrations of C3a and C3b

    From baseline (time 0 months) to 24 months

  • Mean change in dermal microfilaria density on real time Polymerase Chain Reaction at 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)

    24 months

  • +10 more secondary outcomes

Study Arms (2)

Doxycycline

ACTIVE COMPARATOR

* 115 participants will be randomized to oral Doxycycline 100 mg daily for six weeks. * Each capsule contains doxycycline hyclate equivalent to 100 mg of doxycycline base. * Treatment will be initiated in hospital but will be continued at home. * Scheduled study clinic and home visits will be conducted at 6, 12, 24 months and at 2, 4 and 6 weeks respectively for adherence monitoring and assessment of safety.

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

* 115 participants will be randomized to the placebo arm for matching capsules containing no active ingredients daily for six weeks. * Placebo will be initiated in hospital but will be continued at home. * Scheduled study clinic and home visits will be conducted at 6, 12, 24 months and at 2, 4 and 6 weeks respectively for adherence monitoring and assessment of safety.

Other: Placebo

Interventions

DoxycyclineDRUG

* 115 participants will be randomized to either oral Doxycycline 100 mg daily for six weeks. * Treatment will be initiated in hospital but will be continued at home. * Scheduled study clinic visits will be made by the participants at 6, 12 and 24 months. * Each participant will be visited at home at 2, 4 and 6 weeks for adherence monitoring and assessment of safety

Also known as: Doxycycline hyclate
Doxycycline
PlaceboOTHER

\- Placebo (matching capsules containing no active ingredients)

Placebo

Eligibility Criteria

Age8 Years - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Makerere University College of Health Sciences

Kampala, +256, Uganda

RECRUITING

Related Publications (3)

  • Idro R, Ogwang R, Anguzu R, Akun P, Ningwa A, Abbo C, Giannoccaro MP, Kubofcik J, Mwaka AD, Nakamya P, Opar B, Taylor M, Nutman TB, Elliott A, Vincent A, Newton CR, Marsh K. Doxycycline for the treatment of nodding syndrome: a randomised, placebo-controlled, phase 2 trial. Lancet Glob Health. 2024 Jul;12(7):e1149-e1158. doi: 10.1016/S2214-109X(24)00102-5. Epub 2024 May 13.

    PMID: 38754459DERIVED

  • 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.

    PMID: 30841858DERIVED

  • 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.

    PMID: 29382251DERIVED

MeSH Terms

Conditions

Seizures

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Neurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Richard Idro, MMED, PhD

    Makerere University College of Health Sciences

    PRINCIPAL INVESTIGATOR

  • Kevin Marsh, MRCP, DTM&H

    University of Oxford

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Idro, MMED, PhD

CONTACT

+256774274173ridro1@gmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Lecturer

Study Record Dates

First Submitted

March 9, 2016

First Posted

August 1, 2016

Study Start

September 5, 2016

Primary Completion

April 5, 2020

Study Completion

August 5, 2020

Last Updated

February 23, 2017

Record last verified: 2017-02

Data Sharing

IPD Sharing
Will not share

Locations

UG(1)