Excessive Crying in Children With Cerebral Palsy and Communication Deficits -a Fixed-sequence, Crossover Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 131
- 主要终点
- Epidemiologic data (Age and sex).
研究概览
简要总结
Management of excessive crying in children with cerebral palsy and communication deficits [ECCCPCD] was guided by the associated clinical findings and investigations.
详细描述
Pain treatments are frequently hit or miss, trial & error, or because of the fear of litigations, not offered at all, particularly in cerebral palsy. Pain is an under-suspected and under-diagnosed cause of ECCCPCD. It was hypothesized that pain/discomfort was responsible for ECCCPCD, and a vicious cycle of pain-spasm-pain aggravated the pain/discomfort. So, the response of ECCCPCD to treatment guided by clinical findings & investigations was studied.
There was an initial placebo run-in period. This study was a prospective, single-center, interventional, with initial placebo-control, double-blind for initial 110 days, open-label for the next 290 days, fixed-sequence, two treatment, two-period, crossover clinical trial. The placebo run-in period (15 days) was followed by the placebo period (15 days). After a washout period (10 days), drug treatment (360 days) was started depending on the clinical findings and investigations. The drugs used either singly or in various combinations were GABA-B agonists, muscarinic acetylcholine receptor antagonists, benzodiazepines, inhibitors of the vesicular monoamine transporter, antiepileptics, and tricyclic antidepressants. The outcome measure was total, and unexplained mean cry durations in hours per day. The cry duration was measured for one 10-day period while on placebo [days P6-P15], and four 10-day periods while on treatment [T61-70, T241-250, T311-320, and T351-360]. Total and unexplained mean cry durations in hours per day were calculated from 10-day measurements of cry durations. From the 251st day of therapy, the dose was reduced by 5% every week until [ECCCPCD] started to increase. This reduction of the dose was made to confirm the efficacy of drugs and to check if the dosage requirement has reduced after 250 days of treatment. This dose was maintained until the next measurement between T311 and T320. Then the dosages were adjusted as necessary. The caregivers were allowed to volunteer any additional observations of interest. Drug adverse effects were recorded.
Epidemiological data, GMFCS levels, and MAS scores were noted at the time of enrollment. Summary statistics were tabulated and plotted. Paired t-tests and Wilcoxon tests were done to study the statistical significance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The best and most reliable form of research is a double-blind, placebo-controlled study that would eliminate the power of suggestion and prevent bias when patients' outcomes are evaluated thereby improving the reliability of clinical trial results.
Our study was double-blind initially for 110 days until the 70th day of treatment (Figure. 1, Figure. 2.). The caregiver of the participant, the research nurse, and the outcome data collecting nurse were not aware of the drug or drug combination and the dosage. There was no contact between the research nurse, the pharmacist preparing the medicines, and the outcome data collecting nurse. The caregiver of the participant was unaware of other participants' details.
Later, it was an open-label study for 290 days because double blinding for the total period of 400 days may not serve any additional purpose but increases the dropout risk.
入排标准
- 年龄范围
- — 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Medicines used in the study were used in the previous 30 days, and it was impossible to taper off the drugs without worsening of symptoms.
- •Excessive crying due to known causes.
- •Progressive encephalopathies.
研究组 & 干预措施
Placebo-Sequence 1
The placebo contained fructose powder in packets identical to the medicines.
干预措施: Placebo (Other)
Drug-Sequence 2
GABA-B agonists, muscarinic acetylcholine receptor antagonists, inhibitors of the vesicular monoamine transporter, benzodiazepines, antiepileptics, and tricyclic antidepressants were used.
干预措施: Baclofen, Diazepam, Clonazepam, Trihexyphenidyl, Tetrabenazine, Gabapentin, Topiramate, Lamotrigine, Amitriptyline. (Drug)
结局指标
主要结局
Epidemiologic data (Age and sex).
时间窗: 400 days.
Epidemiologic data (age rounded up in years, sex-number of males, females, and transgender, if any).
The Modified Ashworth Scale (MAS) scores
时间窗: 400 days
The Modified Ashworth Scale (MAS) scores from 0 to 4 were used. A higher score means a worse condition.
The Gross Motor Function Classification System (GMFCS) levels
时间窗: 400 days
The gross motor function of children with cerebral palsy was categorized into 5 different levels using the Gross Motor Function Classification System tool. A higher score means a worse condition.
Measurement of both Total and Unexplained cry durations
时间窗: 400 days
Caregivers measured both Total and Unexplained cry durations with a digital watch or a mobile phone in hours: minutes: seconds over five ten-day periods. MM1 while on placebo days 6-15 \[P6-P15\], and four measurements MM2 to MM5 while on treatment days 61-70 \[T61-70\], 241-250 \[T241-250\], 311-320 \[T311-320\], and 351-360 \[T351-360\]. Statistician calculated means of cry duration in hours per day.
次要结局
- Any other changes in the clinical profile observed during the study period and reported by the caregivers.(400 days)
研究者
Dr.Nagabhushana Rao Potharaju
Pediatric Neurologist
Sathbhavana Brain Clinic