Excessive Crying in Children With Cerebral Palsy and Communication Deficits

NCT04523935 | Completed Phase 4

• 1 other identifier: ECCP
• Study Type: interventional
• Target: 131
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Cerebral Palsy; Excessive Crying; Pain

Keywords

Allodynia; Neuropathic pain; Run-in period; childhood onset dystonia; drooling; dysphagia; hyperalgesia; muscle spasticity

Outcome Measures

Primary Outcomes (4)

• Epidemiologic data (Age and sex).

  Epidemiologic data (age rounded up in years, sex-number of males, females, and transgender, if any).

  400 days.

• 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

• 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

• 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 Outcomes (1)

• Any other changes in the clinical profile observed during the study period and reported by the caregivers.

  400 days

Study Arms (2)

Placebo-Sequence 1

PLACEBO COMPARATOR

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

Other: Placebo

Drug-Sequence 2

ACTIVE COMPARATOR

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

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

Interventions

Placebo OTHER

Fructose powder identical with the drugs was used

Also known as: Fruit sugar, levulose.

Placebo-Sequence 1

Baclofen, Diazepam, Clonazepam, Trihexyphenidyl, Tetrabenazine, Gabapentin, Topiramate, Lamotrigine, Amitriptyline. DRUG

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

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

Drug-Sequence 2

Eligibility Criteria

• Age: Up to 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sathbhavana Brain Clinic: lead

Related Publications (25)

• Hagglund 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.

  PMID: 32172660 BACKGROUND

• 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.

  PMID: 30378122 BACKGROUND

• 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.

  PMID: 23606716 BACKGROUND

• 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.

  PMID: 30508224 BACKGROUND

• Alriksson-Schmidt A, Hagglund 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.

  PMID: 26880375 BACKGROUND

• 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):e20171002. doi: 10.1542/peds.2017-1002.

  PMID: 28562301 BACKGROUND

• 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.

  PMID: 28509356 BACKGROUND

• 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.

  PMID: 23858420 BACKGROUND

• 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. No abstract available.

  PMID: 23574476 BACKGROUND

• 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. doi: 10.1155/2013/813867.

  PMID: 24308022 BACKGROUND

• 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.

  PMID: 22014321 BACKGROUND

• 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.

  PMID: 31521713 BACKGROUND

• Tedroff K, Gyllensvard M, Lowing 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.

  PMID: 31526138 BACKGROUND

• 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.

  PMID: 21148657 BACKGROUND

• 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.

  PMID: 29882358 BACKGROUND

• 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.

  PMID: 18504511 BACKGROUND

• 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.

  PMID: 31597591 BACKGROUND

• 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.

  PMID: 28638303 BACKGROUND

• 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.

  PMID: 28503628 BACKGROUND

• 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. doi: 10.1001/jama.296.13.1602.

  PMID: 17018805 BACKGROUND

• Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet. 1978 Sep 23;2(8091):654-7. doi: 10.1016/s0140-6736(78)92762-9.

  PMID: 80579 BACKGROUND

• 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.

  PMID: 31328797 BACKGROUND

• 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.

  PMID: 18754902 BACKGROUND

• 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.

  PMID: 30304925 BACKGROUND

• 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.

  PMID: 25389436 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy; Pain; Hyperalgesia; Neuralgia; Dystonic Disorders; Sialorrhea; Deglutition Disorders; Muscle Spasticity

Interventions

Fructose; Baclofen; Diazepam; Clonazepam; Trihexyphenidyl; Tetrabenazine; Gabapentin; Topiramate; Lamotrigine; Amitriptyline

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Peripheral Nervous System Diseases; Neuromuscular Diseases; Movement Disorders; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Quinolizines; Amines; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Triazines; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds

Study Officials

• Nagabhushana Rao Potharaju, BScMDDCHDM

  Sathbhavana Brain Clinic, Hyderabad, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Neurologist

Model Details: 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.

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 24, 2020
• Study Start: December 7, 2005
• Primary Completion: August 4, 2020
• Study Completion: August 4, 2020
• Last Updated: October 28, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: One year
• Access Criteria: For meta-analysis or a similar study