Ignite Creation Date:
2025-12-26 @ 10:57 AM
Ignite Modification Date:
2025-12-29 @ 2:11 PM
Study NCT ID:
NCT04270708
Status:
UNKNOWN
Last Update Posted:
2020-02-17
First Post:
2020-02-13
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intranasal Dexmedetomidine vs Oral Triclofos Sodium for EEG in Children With Autism
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001321', 'term': 'Autistic Disorder'}], 'ancestors': [{'id': 'D000067877', 'term': 'Autism Spectrum Disorder'}, {'id': 'D002659', 'term': 'Child Development Disorders, Pervasive'}, {'id': 'D065886', 'term': 'Neurodevelopmental Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020927', 'term': 'Dexmedetomidine'}, {'id': 'C004345', 'term': 'triclofos'}], 'ancestors': [{'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['CARE_PROVIDER', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'SUPPORTIVE_CARE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2020-03-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-02', 'completionDateStruct': {'date': '2022-08-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-02-13', 'studyFirstSubmitDate': '2020-02-13', 'studyFirstSubmitQcDate': '2020-02-13', 'lastUpdatePostDateStruct': {'date': '2020-02-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-03-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximal Sedation Depth', 'timeFrame': 'Within 90 minutes', 'description': 'Maximal Sedation Depth by the University of Michigan Sedation Scale (UMSS)'}, {'measure': 'Technician satisfaction from sedation', 'timeFrame': 'Within 90 minutes', 'description': 'Technician Ability to complete exam in satisfactory fashion - VAS score'}], 'secondaryOutcomes': [{'measure': 'Neurologist satisfaction from EEG motion artifact', 'timeFrame': 'Within 7 days', 'description': 'Neurologist satisfaction from EEG motion artifact - VAS score'}, {'measure': 'Compliance with IN vs Oral Delivery', 'timeFrame': 'Immediate upon administration', 'description': 'Compliance with IN vs Oral Delivery - Successful drug administration Y/N?'}, {'measure': 'Resistance to drug administration (1-10 scale)', 'timeFrame': 'Immediate upon administration', 'description': 'Resistance to drug administration (1-10 scale): Crying / spitting or Complete or Partial Rejection for TFS/IN DEX'}, {'measure': 'Achieving sedation following single dose', 'timeFrame': 'Within 45 minutes', 'description': 'Achieving sedation following single dose of Dexmed vs TFS'}, {'measure': 'Achieving sedation following rescue dose', 'timeFrame': 'within 90 minutes', 'description': 'Achieving sedation following additional rescue dose of Dexmed vs TFS'}, {'measure': 'Sedation onset, duration and recovery periods', 'timeFrame': 'Within 4 hours.', 'description': 'Sedation onset, duration and recovery periods'}, {'measure': 'Adverse Events', 'timeFrame': 'Within 4 hours.', 'description': 'Sedation associated adverse events'}]}, 'oversightModule': {'isUsExport': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sedation'], 'conditions': ['Autistic Disorder']}, 'referencesModule': {'references': [{'pmid': '29701730', 'type': 'RESULT', 'citation': 'Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee LC, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino JN, Vehorn A, Shenouda J, Hall-Lande J, Van Naarden Braun K, Dowling NF. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveill Summ. 2018 Apr 27;67(6):1-23. doi: 10.15585/mmwr.ss6706a1.'}, {'pmid': '28455770', 'type': 'RESULT', 'citation': 'Keller R, Basta R, Salerno L, Elia M. Autism, epilepsy, and synaptopathies: a not rare association. Neurol Sci. 2017 Aug;38(8):1353-1361. doi: 10.1007/s10072-017-2974-x. Epub 2017 Apr 28.'}, {'pmid': '9060867', 'type': 'RESULT', 'citation': 'Thoresen M, Henriksen O, Wannag E, Laegreid L. Does a sedative dose of chloral hydrate modify the EEG of children with epilepsy? Electroencephalogr Clin Neurophysiol. 1997 Feb;102(2):152-7. doi: 10.1016/s0921-884x(96)96509-1.'}, {'pmid': '24532346', 'type': 'RESULT', 'citation': 'Nordt SP, Rangan C, Hardmaslani M, Clark RF, Wendler C, Valente M. Pediatric chloral hydrate poisonings and death following outpatient procedural sedation. J Med Toxicol. 2014 Jun;10(2):219-22. doi: 10.1007/s13181-013-0358-z.'}, {'pmid': '8632499', 'type': 'RESULT', 'citation': 'Sing K, Erickson T, Amitai Y, Hryhorczuk D. Chloral hydrate toxicity from oral and intravenous administration. J Toxicol Clin Toxicol. 1996;34(1):101-6. doi: 10.3109/15563659609020242.'}, {'pmid': '3706808', 'type': 'RESULT', 'citation': 'Hirsch IA, Zauder HL. Chloral hydrate: a potential cause of arrhythmias. Anesth Analg. 1986 Jun;65(6):691-2. No abstract available.'}, {'pmid': '31447530', 'type': 'RESULT', 'citation': 'Grissinger M. Chloral Hydrate: Is It Still Being Used? Are There Safer Alternatives? P T. 2019 Aug;44(8):444-459.'}, {'pmid': '31292919', 'type': 'RESULT', 'citation': 'Kaplan E, Daka A, Weissbach A, Kraus D, Kadmon G, Milkh R, Nahum E. Triclofos Sodium for Pediatric Sedation in Non-Painful Neurodiagnostic Studies. Paediatr Drugs. 2019 Oct;21(5):371-378. doi: 10.1007/s40272-019-00346-6.'}, {'pmid': '22704249', 'type': 'RESULT', 'citation': 'Mason KP, Lubisch N, Robinson F, Roskos R, Epstein MA. Intramuscular dexmedetomidine: an effective route of sedation preserves background activity for pediatric electroencephalograms. J Pediatr. 2012 Nov;161(5):927-32. doi: 10.1016/j.jpeds.2012.05.011. Epub 2012 Jun 15.'}, {'pmid': '30982953', 'type': 'RESULT', 'citation': 'Liu H, Sun M, Zhang J, Tian Q, Yu Q, Liu Y, Yang F, Li S, Tu S. Determination of the 90% effective dose of intranasal dexmedetomidine for sedation during electroencephalography in children. Acta Anaesthesiol Scand. 2019 Aug;63(7):847-852. doi: 10.1111/aas.13372. Epub 2019 Apr 14.'}, {'pmid': '26814037', 'type': 'RESULT', 'citation': 'Baier NM, Mendez SS, Kimm D, Velazquez AE, Schroeder AR. Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing. Paediatr Anaesth. 2016 Mar;26(3):280-5. doi: 10.1111/pan.12851.'}, {'pmid': '25246305', 'type': 'RESULT', 'citation': 'Gumus H, Bayram AK, Poyrazoglu HG, Canpolat DG, Per H, Canpolat M, Yildiz K, Kumandas S. Comparison of Effects of Different Dexmedetomidine and Chloral Hydrate Doses Used in Sedation on Electroencephalography in Pediatric Patients. J Child Neurol. 2015 Jul;30(8):983-8. doi: 10.1177/0883073814549582. Epub 2014 Sep 22.'}, {'pmid': '24823763', 'type': 'RESULT', 'citation': 'Fernandes ML, Oliveira WM, Santos Mdo C, Gomez RS. Sedation for electroencephalography with dexmedetomidine or chloral hydrate: a comparative study on the qualitative and quantitative electroencephalogram pattern. J Neurosurg Anesthesiol. 2015 Jan;27(1):21-5. doi: 10.1097/ANA.0000000000000077.'}, {'pmid': '12472704', 'type': 'RESULT', 'citation': 'Kogan A, Katz J, Efrat R, Eidelman LA. Premedication with midazolam in young children: a comparison of four routes of administration. Paediatr Anaesth. 2002 Oct;12(8):685-9. doi: 10.1046/j.1460-9592.2002.00918.x.'}, {'pmid': '31862730', 'type': 'RESULT', 'citation': 'Poonai N, Spohn J, Vandermeer B, Ali S, Bhatt M, Hendrikx S, Trottier ED, Sabhaney V, Shah A, Joubert G, Hartling L. Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review. Pediatrics. 2020 Jan;145(1):e20191623. doi: 10.1542/peds.2019-1623.'}, {'pmid': '26936022', 'type': 'RESULT', 'citation': 'Li BL, Zhang N, Huang JX, Qiu QQ, Tian H, Ni J, Song XR, Yuen VM, Irwin MG. A comparison of intranasal dexmedetomidine for sedation in children administered either by atomiser or by drops. Anaesthesia. 2016 May;71(5):522-8. doi: 10.1111/anae.13407. Epub 2016 Mar 3.'}, {'pmid': '28347608', 'type': 'RESULT', 'citation': 'Xie Z, Shen W, Lin J, Xiao L, Liao M, Gan X. Sedation effects of intranasal dexmedetomidine delivered as sprays versus drops on pediatric response to venous cannulation. Am J Emerg Med. 2017 Aug;35(8):1126-1130. doi: 10.1016/j.ajem.2017.03.021. Epub 2017 Mar 18.'}, {'pmid': '21318594', 'type': 'RESULT', 'citation': 'Iirola T, Vilo S, Manner T, Aantaa R, Lahtinen M, Scheinin M, Olkkola KT. Bioavailability of dexmedetomidine after intranasal administration. Eur J Clin Pharmacol. 2011 Aug;67(8):825-31. doi: 10.1007/s00228-011-1002-y. Epub 2011 Feb 12.'}]}, 'descriptionModule': {'briefSummary': 'Children with Autistic Spectrum Disorder (ASD) often undergo an Electroencephalography (EEG) as part of routine work up. These children present a challenge to successful EEG execution, due to a lack of co-operation, and thus, are often in need of sedation. Historically we have used orally administered, Triclofos Sodium (TFS) - pharmacologically and physiologically similar to chloral hydrate, for sedation in this age group. However success using this drug is limited to approximately 75% in those aged 5 years and above, and possibly lower in this age group when associated with a diagnosis of ASD. The medication is often poorly tolerated by the oral route, and involves patient agitation, spiting (with incomplete drug ingestion), and immediate vomiting upon administration. Recently we have introduced Intra-nasal Dexmedetomidine (IN DEX), with an initial impression of much improved drug acceptance and possibly improved efficacy over TFS.\n\nWe designed this pilot study, with the aim of comparing efficacy, tolerance of drug administration and adverse events between TFS and IN DEX, with the goal of generating initial results as well as feasibility of recruitment for a larger trial.', 'detailedDescription': "Study participants will be allocated, amongst patients invited for routine EEG monitoring in the hospitals EEG facility. All patients will be fasted on arrival, with a recommendation to awaken early on the day of the planned examination.\n\nPatients aged 4yrs and above, with a diagnosis of ASD will be allocated and investigated for fulfillment of inclusion and exclusion criteria for study participation. The legal guardians of patients meeting study criteria will be approached for study participation consent. Patients declining consent will be treated with TFS as per current protocol. Patients for whom consent is attained will comprise the study group.\n\nStudy group patients will be randomized for treatment and stratified according to age groups: 4-7, 8-12, 12-18. Treatment will consist of 2 alternative pathways:\n\nOral Trichlofos Sodium (TFS) Pathway:\n\n1. Initial Drug dose: Patients will be treated orally with 50mg/kg of TFS to maximum of 2000gr.\n2. Failure to achieve sedate state 45 minutes after drug administration will enable an additional oral dose of 25mg/kg.\n3. Patients failing to fall asleep following second drug dose will be regarded as treatment failure.\n4. Rescue therapy according to physician's choice can be instituted (Dexmed or Neuleptil).\n\nIntranasal Dexmedetomidine (IN DEX) Pathway:\n\n1. Initial drug dose: Patients will be treated with IN 3mcg/kg of Dexmedetomidine to max dose of 150mcg. The drug will be delivered through MAD nasal atomizer.\n2. Failure to achieve sedate state 45 minutes after drug administration will enable an additional dose of IN 1.5mcg/kg by MAD device.\n3. Paitients failing to fall asleep following second drug dose will be regarded as treatment failure.\n4. Rescue therapy according to physician's choice can be instituted (Neuleptil not recommended due to drug interactions).\n\nAll sedated children will be connected to monitoring including ECG chest leads in addition to oxygen pulse saturation monitoring.\n\nPrimary outcome assessment: Sedation depth by UMSS will be assessed by the EEG technician, who will be blinded to the drug used for sedation.\n\nSecondary outcome assessment:\n\n1. Satisfaction from sedation depth for completing exam by blinded technician on VAS score.\n2. EEG motion artifact by interpreting neurologist, blinded to study drug on VAS score.\n3. All other secondary outcomes from drug administration to discharge, including adverse events and needed interventions, will be documented by the nurse who is not blinded to administered drug.\n4. ECG monitoring for determination of HR or arrhythmia\n5. Assessing incidence of bradycardia, hypotension and their severity:\n\n a. HR and BP age related normal value chart to be used as reference. b. Bradycardia and Hypotension determined in relation to lower normal value for age: i. Mild\\<10% decrease from normal value ii. Moderate 10-20% decrease from normal value iii. Severe \\>20% or signs of hemodynamic compromise\n\n Ethics: This study is a comparison of two medications currently under routine use for performing sedated EEG's in our medical center. The study will be authorized by the Rabin Campus Helsinki Committee. Informed consent will be requested from the accompanying legal guardian.\n\n Statistics: Based on our experience, we assume a 70% success rate for sedation using TFS and a 90% success rate for IN DEX. Using an alpha of 0.05 and 80% power, two groups of 62 patients would be needed, to demonstrate statistical significance.\n\n This trial is planned as a pilot study aimed at assessing drug effects and recruitment rate, over a limited time period of up to 2 year, or up to 200 patiens (100 TFS + 100 IN DEX).\n\n Randomization and age stratification: Patient allocation will be determined according to an age stratified randomization table. Patients will be stratified by 3 age groups: 4-7, 8-12, 12-18.\n\n Funding: No funding has been allocated for this study. Study will be conducted using routine medications in current practice without additional cost."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '19 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Children aged 4-18 yrs referred for an EEG under sedation..\n2. A Neurologist derived diagnosis of Autistic Spectrum Disorder (ASD).\n3. ASA 1 or 2\n\nExclusion Criteria:\n\n1. Allergy to study drug\n2. Congenital heart disease, bradycardia \\< 60 or know arrhythmia/AV block.\n3. Vasoactive drugs or treatment for arterial HTN.\n4. Known Renal dysfunction Creatinine Clearance \\< 30% or known Liver dysfunction (Elevated LFT's).\n5. Concurrent Treatment with drugs know to interact with Dexmedetomidine:\n\n 1. Atipical Antipsychotics / Phenothiazines\n 2. Tricyclic anti-depressents\n 3. Lacosamide treatment - Antiepileptic.\n 4. PDE V inhibitors (Viagra)\n 5. Beta-blockers\n 6. Phenothiazines\n 7. First generation Anti-histamines\n6. Significant rhinorrhea."}, 'identificationModule': {'nctId': 'NCT04270708', 'briefTitle': 'Intranasal Dexmedetomidine vs Oral Triclofos Sodium for EEG in Children With Autism', 'organization': {'class': 'OTHER', 'fullName': 'Rabin Medical Center'}, 'officialTitle': 'Intranasal Dexmedetomidine vs Oral Triclofos Sodium Sedation for Children With Autism Undergoing Electroencephalograms - A Randomized Controlled Trial.', 'orgStudyIdInfo': {'id': '0090-20-RMC'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dexmedetomidine', 'description': 'Intranasal Dexmedetomidine 3mcg/kg', 'interventionNames': ['Drug: Dexmedetomidine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Triclofos', 'description': 'Oral Triclofos Sodium 50mg/kg', 'interventionNames': ['Drug: Triclofos 100 MG/ML']}], 'interventions': [{'name': 'Dexmedetomidine', 'type': 'DRUG', 'description': 'Patients with Autism will be treated with intranasal Dexmedetomidine as a sedative for EEG', 'armGroupLabels': ['Dexmedetomidine']}, {'name': 'Triclofos 100 MG/ML', 'type': 'DRUG', 'description': 'Patients with Autism will be treated with oral Triclofos as a sedative for EEG', 'armGroupLabels': ['Triclofos']}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rabin Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': "Director of Pediatric Sedation Services, Schneider Children's Medical Center of Israel", 'investigatorFullName': 'Eytan Kaplan', 'investigatorAffiliation': 'Rabin Medical Center'}}}}