Management of Excessive Crying in Cerebral Palsy

Management of Excessive Crying in Cerebral Palsy -A Placebo-controlled, Fixed-sequence, Crossover Clinical Trial.

Sponsors

Lead Sponsor: Sathbhavana Brain Clinic

Source Sathbhavana Brain Clinic
Brief Summary

Management of Excessive Crying in cerebral palsy (ECCP) 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 ECCP. It was hypothesized that pain/discomfort was responsible for ECCP, and a vicious cycle of pain-spasm-pain aggravated the pain/discomfort. So, the response of ECCP 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 a change in total, and unexplained mean cry durations in hours per day. Total and unexplained mean cry durations in hours per day were calculated from 10-day measurements of cry durations. 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]. From the 251st day of therapy, the dose was reduced by 5% every week until ECCP 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.

Summary statistics were tabulated and plotted. Paired t-tests and Wilcoxon tests were done to study the statistical significance.

Overall Status Completed
Start Date December 7, 2005
Completion Date August 4, 2020
Primary Completion Date August 4, 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Total and unexplained mean cry durations in hours per day. 400 days.
Enrollment 131
Condition
Intervention

Intervention Type: Other

Intervention Name: Placebo

Description: Fructose powder identical with the drugs was used

Arm Group Label: Placebo-Sequence 1

Other Name: Fruit sugar, levulose.

Intervention Type: Drug

Intervention Name: Baclofen, Diazepam, Clonazepam, Trihexyphenidyl, Tetrabenazine, Gabapentin, Topiramate, Lamotrigine, Amitriptyline.

Description: Drugs were used either singly or in combination guided by clinical findings and investigations.

Arm Group Label: Drug-Sequence 2

Other Name: Baclofen(Liofen®),Diazepam,(Valium®),Clonazepam,(Klonopin®),Trihexyphenidyl(Artane®),Tetrabenazine(Xenazine®),Gabapentin(Neurontin®),Topiramate(Topamax®),Lamotrigine(Lamictal®),Amitriptyline(Elavil®)

Eligibility

Criteria:

Inclusion Criteria:

- A child with cerebral palsy and not able to communicate the reason for excessive crying because of young age or global developmental delay/profound intellectual retardation.

- Excessive crying of >7.5 hours daily for 30 consecutive days unresponsive to treatment by the pediatrician, orthopedic surgeon, gastroenterologist, and physiotherapist.

- Minimum cry intensity for recording: If the intensity of crying was so high that the caregiver was not able to hear radio, TV, or another person talking to her [sitting near her], the cry duration was recorded.

- History and physical examination were suggestive of chronic static encephalopathy.

- Motor impairment could be explained with an insult that occurred in the developing fetal or infant brain.

- MRI abnormalities were consistent with CP.

- If MRI was normal, history, physical examination, and investigations must have excluded a progressive neurologic disease.

Exclusion Criteria:

- 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.

- Cause of ECCP was known.

- Crying reduced on the treatment of provocative factors that increased spasticity.

- Progressive encephalopathies.

Gender: All

Minimum Age: N/A

Maximum Age: 15 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Nagabhushana Rao Potharaju, BScMDDCHDM Principal Investigator Sathbhavana Brain Clinic, Hyderabad, India
Verification Date

August 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Sathbhavana Brain Clinic

Investigator Full Name: Dr.Nagabhushana Rao Potharaju

Investigator Title: Pediatric Neurologist

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Placebo-Sequence 1

Type: Placebo Comparator

Description: The placebo contained fructose powder in packets identical to the medicines.

Label: Drug-Sequence 2

Type: Active Comparator

Description: GABA-B agonists, muscarinic acetylcholine receptor antagonists, inhibitors of the vesicular monoamine transporter, benzodiazepines, antiepileptics, and tricyclic antidepressants were used.

Acronym ECCP
Patient Data Yes
Study Design Info

Allocation: Non-Randomized

Intervention Model: Crossover Assignment

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

Masking: Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description: It was double-blind initially for 110 days until the 70th day of treatment. The caregiver of the subject was unaware of other participants' details. There was no contact between the research nurse, the pharmacist preparing the medicines, and the outcome data collecting nurse. None of them knew the drug or drug combination and the dosage. Later, it was an open-label study.

Source: ClinicalTrials.gov