Clinical trial NCT04523935: Excessive Crying in Children With Cerebral Palsy and Communication Deficits
Official title: Excessive Crying in Children With Cerebral Palsy and Communication Deficits -a Fixed-sequence, Crossover Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerebral Palsy
Excessive Crying
Pain
Keywords: Allodynia
Neuropathic pain
Run-in period
childhood onset dystonia
drooling
dysphagia
hyperalgesia
muscle spasticity
Lead sponsor: Sathbhavana Brain Clinic
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 131
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: There was an initial placebo run-in period. This clinical trial 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.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Management of excessive crying in children with cerebral palsy and communication deficits \[ECCCPCD\] was guided by the associated clinical findings and investigations.

Detailed description: 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.

Eligibility criteria: 1. A child with cerebral palsy under the age of 15 years and could not communicate the reason for excessive crying because of young age or global developmental delay/profound intellectual retardation.
2. Excessive crying of \>7.5 hours daily for 30 consecutive days unresponsive to treatment by the pediatrician, orthopedic surgeon, gastroenterologist, and physiotherapist.
3. Minimum cry intensity for recording: If the intensity of crying was so high that the caregiver could not hear radio, TV, or another person talking to her \[sitting near her\], the cry duration was recorded.
4. History, clinical, and neuroimaging findings (structural MRI) were suggestive of chronic static encephalopathy.
5. Motor impairment could be explained by an insult that occurred in the developing fetal or infant brain.

Exclusion Criteria:

1. 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.
2. Excessive crying due to known causes.
3. Progressive encephalopathies.

Primary outcomes:
measure: Epidemiologic data (Age and sex).
timeFrame: 400 days.
measure: The Gross Motor Function Classification System (GMFCS) levels
timeFrame: 400 days
measure: The Modified Ashworth Scale (MAS) scores
timeFrame: 400 days
measure: Measurement of both Total and Unexplained cry durations
timeFrame: 400 days
Secondary outcomes:
measure: Any other changes in the clinical profile observed during the study period and reported by the caregivers.
timeFrame: 400 days
Other outcomes:
Locations:
Study officials:
affiliation: Sathbhavana Brain Clinic, Hyderabad, India
name: Nagabhushana Rao Potharaju, BScMDDCHDM
role: PRINCIPAL_INVESTIGATOR
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