Doxycycline for the Treatment of Nodding Syndrome: A Phase II, Randomised Placebo Controlled Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Proportion of patients with antibodies to Neuron Surface Proteins (NSPs) or leiomodin at 24 months.
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Doxycycline
- 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.
干预措施: Doxycycline (Drug)
Placebo
- 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.
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of patients with antibodies to Neuron Surface Proteins (NSPs) or leiomodin at 24 months.
时间窗: 24 months
次要结局
- Mean change in serum concentrations of antibodies to NSPs or leiomodin(From baseline (time 0 months) to 24 months)
- Proportion of patients with interictal epileptiform discharges on 30-minute diagnostic EEG(24 months)
- Proportion of participants with Gross Motor Function Classification System (GMFCS) scores 3-5(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)
- Proportion of participants with mental health disorders on the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)(24 months)
- Mean change in cogstate scores(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(From baseline (time 0 months) to 24 months)
- Incidence rate of non-nodding syndrome sick clinic visits and all cause sick clinic visits(24 months)
- The proportion of participants with stunting (height for age Z-scores <-3 SD)(24 months)
- The proportion of participants with wasting (weight for height Z-scores <-3 SD)(24 months)
- All-cause mortality(24 months)
- Incidence rate of all-cause hospital admissions(24 months)
研究者
College of Health Sciences
Senior Lecturer
Makerere University