Excessive Crying in Children With Cerebral Palsy and Communication Deficits

Pain Clinical Trial

— ECCCPCD  

Official title:

Excessive Crying in Children With Cerebral Palsy and Communication Deficits -a Fixed-sequence, Crossover Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04523935
• Other study ID #: ECCP
• Status: Completed
• Phase: Phase 4
• Start date: December 7, 2005
• Est. completion date: August 4, 2020

Study information

• Verified date: October 2021
• Source: Sathbhavana Brain Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: August 4, 2020
• Est. primary completion date: August 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Palsy
• Pain

Intervention

Other:
• Placebo
Fructose powder identical with the drugs was used

Drug:
• Baclofen, Diazepam, Clonazepam, Trihexyphenidyl, Tetrabenazine, Gabapentin, Topiramate, Lamotrigine, Amitriptyline.
Drugs were used either singly or in combination guided by clinical findings and investigations.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sathbhavana Brain Clinic

References & Publications (25)

Alriksson-Schmidt A, Hägglund G. Pain in children and adolescents with cerebral palsy: a population-based registry study. Acta Paediatr. 2016 Jun;105(6):665-70. doi: 10.1111/apa.13368. Epub 2016 Mar 30. — View Citation

Asaro J, Robinson CA, Levy PT. Visceral Hyperalgesia: When to Consider Gabapentin Use in Neonates-Case Study and Review. Child Neurol Open. 2017 Feb 10;4:2329048X17693123. doi: 10.1177/2329048X17693123. eCollection 2017 Jan-Dec. — View Citation

Barney CC, Krach LE, Rivard PF, Belew JL, Symons FJ. Motor function predicts parent-reported musculoskeletal pain in children with cerebral palsy. Pain Res Manag. 2013 Nov-Dec;18(6):323-7. — View Citation

Bax M, Tydeman C, Flodmark O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA. 2006 Oct 4;296(13):1602-8. — View Citation

Baxter P. Comorbidities of cerebral palsy need more emphasis--especially pain. Dev Med Child Neurol. 2013 May;55(5):396. doi: 10.1111/dmcn.12137. — View Citation

Blackman JA, Svensson CI, Marchand S. Pathophysiology of chronic pain in cerebral palsy: implications for pharmacological treatment and research. Dev Med Child Neurol. 2018 Sep;60(9):861-865. doi: 10.1111/dmcn.13930. Epub 2018 Jun 7. Review. — View Citation

Calis EA, Veugelers R, Sheppard JJ, Tibboel D, Evenhuis HM, Penning C. Dysphagia in children with severe generalized cerebral palsy and intellectual disability. Dev Med Child Neurol. 2008 Aug;50(8):625-30. doi: 10.1111/j.1469-8749.2008.03047.x. — View Citation

Fairhurst C, Shortland A, Chandler S, Will E, Scrutton D, Simonoff E, Baird G. Factors associated with pain in adolescents with bilateral cerebral palsy. Dev Med Child Neurol. 2019 Aug;61(8):929-936. doi: 10.1111/dmcn.14113. Epub 2018 Dec 3. — View Citation

Hägglund G, Burman-Rimstedt A, Czuba T, Alriksson-Schmidt AI. Self-versus Proxy-Reported Pain in Children with Cerebral Palsy: A Population-Based Registry Study of 3783 Children. J Prim Care Community Health. 2020 Jan-Dec;11:2150132720911523. doi: 10.1177/2150132720911523. — View Citation

Hauer J, Houtrow AJ; SECTION ON HOSPICE AND PALLIATIVE MEDICINE, COUNCIL ON CHILDREN WITH DISABILITIES. Pain Assessment and Treatment in Children With Significant Impairment of the Central Nervous System. Pediatrics. 2017 Jun;139(6). pii: e20171002. doi: 10.1542/peds.2017-1002. Review. — View Citation

Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet. 1978 Sep 23;2(8091):654-7. — View Citation

Li S, Shi S, Chen F, Lin J. The effects of baclofen for the treatment of gastroesophageal reflux disease: a meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2014;2014:307805. doi: 10.1155/2014/307805. Epub 2014 Oct 20. Review. — View Citation

Ostojic K, Paget S, Kyriagis M, Morrow A. Acute and Chronic Pain in Children and Adolescents With Cerebral Palsy: Prevalence, Interference, and Management. Arch Phys Med Rehabil. 2020 Feb;101(2):213-219. doi: 10.1016/j.apmr.2019.08.475. Epub 2019 Sep 12. — View Citation

Ostojic K, Paget SP, Morrow AM. Management of pain in children and adolescents with cerebral palsy: a systematic review. Dev Med Child Neurol. 2019 Mar;61(3):315-321. doi: 10.1111/dmcn.14088. Epub 2018 Oct 31. — View Citation

Parkinson KN, Dickinson HO, Arnaud C, Lyons A, Colver A; SPARCLE group. Pain in young people aged 13 to 17 years with cerebral palsy: cross-sectional, multicentre European study. Arch Dis Child. 2013 Jun;98(6):434-40. doi: 10.1136/archdischild-2012-303482. Epub 2013 Apr 20. — View Citation

Penner M, Xie WY, Binepal N, Switzer L, Fehlings D. Characteristics of pain in children and youth with cerebral palsy. Pediatrics. 2013 Aug;132(2):e407-13. doi: 10.1542/peds.2013-0224. Epub 2013 Jul 15. — View Citation

Ramstad K, Jahnsen R, Skjeldal OH, Diseth TH. Characteristics of recurrent musculoskeletal pain in children with cerebral palsy aged 8 to 18 years. Dev Med Child Neurol. 2011 Nov;53(11):1013-8. doi: 10.1111/j.1469-8749.2011.04070.x. — View Citation

Sacha GL, Foreman MG, Kyllonen K, Rodriguez RJ. The Use of Gabapentin for Pain and Agitation in Neonates and Infants in a Neonatal ICU. J Pediatr Pharmacol Ther. 2017 May-Jun;22(3):207-211. doi: 10.5863/1551-6776-22.3.207. — View Citation

Samal P, Goyal V, Makharia GK, Das CJ, Gorthi SP, Y VV, Singh MB, Srivastava MVP. Transfer Dysphagia Due to Focal Dystonia. J Mov Disord. 2018 Sep;11(3):129-132. doi: 10.14802/jmd.17081. Epub 2018 Sep 30. — View Citation

Speyer R, Cordier R, Kim JH, Cocks N, Michou E, Wilkes-Gillan S. Prevalence of drooling, swallowing, and feeding problems in cerebral palsy across the lifespan: a systematic review and meta-analyses. Dev Med Child Neurol. 2019 Nov;61(11):1249-1258. doi: 10.1111/dmcn.14316. Epub 2019 Jul 22. — View Citation

St James-Roberts I, Garratt R, Powell C, Bamber D, Long J, Brown J, Morris S, Dyson S, Morris T, Bhupendra Jaicim N. A support package for parents of excessively crying infants: development and feasibility study. Health Technol Assess. 2019 Oct;23(56):1-144. doi: 10.3310/hta23560. — View Citation

Suter MR, Wen YR, Decosterd I, Ji RR. Do glial cells control pain? Neuron Glia Biol. 2007 Aug;3(3):255-68. doi: 10.1017/S1740925X08000100. — View Citation

Tedroff K, Gyllensvärd M, Löwing K. Prevalence, identification, and interference of pain in young children with cerebral palsy: a population-based study. Disabil Rehabil. 2021 May;43(9):1292-1298. doi: 10.1080/09638288.2019.1665719. Epub 2019 Sep 17. — View Citation

Voscopoulos C, Lema M. When does acute pain become chronic? Br J Anaesth. 2010 Dec;105 Suppl 1:i69-85. doi: 10.1093/bja/aeq323. Review. — View Citation

Westbom L, Rimstedt A, Nordmark E. Assessments of pain in children and adolescents with cerebral palsy: a retrospective population-based registry study. Dev Med Child Neurol. 2017 Aug;59(8):858-863. doi: 10.1111/dmcn.13459. Epub 2017 May 16. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epidemiologic data (Age and sex).	Epidemiologic data (age rounded up in years, sex-number of males, females, and transgender, if any).	400 days.
Primary	The Gross Motor Function Classification System (GMFCS) levels	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.	400 days
Primary	The Modified Ashworth Scale (MAS) scores	The Modified Ashworth Scale (MAS) scores from 0 to 4 were used. A higher score means a worse condition.	400 days
Primary	Measurement of both Total and Unexplained cry durations	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.	400 days
Secondary	Any other changes in the clinical profile observed during the study period and reported by the caregivers.	Any other changes in the clinical profile (frequency changes) observed during the study period were reported by the caregivers. The number and percentages of children with the change were calculated.	400 days