Ignite Creation Date:
2025-12-25 @ 4:48 AM
Ignite Modification Date:
2025-12-26 @ 3:50 AM
Study NCT ID:
NCT05379218
Status:
COMPLETED
Last Update Posted:
2024-03-07
First Post:
2021-11-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
RIC in HIE: A Safety and Feasibility Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020925', 'term': 'Hypoxia-Ischemia, Brain'}], 'ancestors': [{'id': 'D002545', 'term': 'Brain Ischemia'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D002534', 'term': 'Hypoxia, Brain'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D000860', 'term': 'Hypoxia'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 32}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-01-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2024-02-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-03-05', 'studyFirstSubmitDate': '2021-11-25', 'studyFirstSubmitQcDate': '2022-05-12', 'lastUpdatePostDateStruct': {'date': '2024-03-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-05-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-02-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'aEEG', 'timeFrame': '4 hours', 'description': 'Background pattern/s (and relative duration) before (2 hours) and after (2 hours) RIC.\n\nBackground pattern/s include classifying the tracings by lower margin of tracing in microvolts and upper margin of tracing in microvolts. Normal aEEG pattern vs continuous normal voltage, discontinuous normal voltage, burst suppression, low voltage, or flat +/- seizures.\n\nNormal aEEG pattern: lower margin \\>5 microvolts and upper margin \\>10 microvolts.\n\nPresence of sleep-wake cycles and seizures.'}, {'measure': 'Biomarkers', 'timeFrame': '72 hours', 'description': 'Blood collected at 72 hours will be used to measure biomarkers for brain injury: S100B, blood brain-derived neurotrophic factor, total Tau, and neuron-specific enolase as measured in nanograms per milliliter. Blood will also be bio banked for additional immune-related analysis, but will not be used for genetic analysis.'}, {'measure': 'MRI including diffusion-weighted imaging and spectroscopy', 'timeFrame': '7 days', 'description': 'MRI will be done between day 4 and 7 of age, as per standard of care, and scored for injury severity. MRI will be scored according to Weeke et al. criteria (Journal of Pediatrics 2018).'}, {'measure': 'Number of patients with cognitive, motor, and/or language impairment at 18-24 months corrected age defined as < 85 (impairment) and <70 (severe impairment) on the Bayley Scales of Infant and Toddler Development (3rd edition)', 'timeFrame': '18-24 months', 'description': '1. Neurodevelopment: cognitive, motor, and language impairment defined as a Bayley Scales of Infant and Toddler Development (3rd edition) scores \\< 85 (impairment) and \\<70 (severe impairment).\n2. Deafness or hearing impairment.\n3. Blindness or visual impairment.'}, {'measure': 'Number of patients with deafness or hearing impairment on decibel scale at 18-24 months corrected age', 'timeFrame': '18-24 months', 'description': 'Deafness or hearing impairment on decibel scale'}, {'measure': 'Number of patients with blindness or visual impairment on visual acuity scale at 18-24 months corrected age', 'timeFrame': '18-24 months', 'description': 'Blindness or visual impairment on visual acuity scale'}], 'primaryOutcomes': [{'measure': 'RIC cycles administered as planned (Y/N)', 'timeFrame': '72 hours', 'description': 'Designated RIC cycles are administered as planned (dichotomous variable)'}, {'measure': 'Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]', 'timeFrame': '72 hours', 'description': 'Frequency of limb ischemia, incidence of RIC interruption and rescue intervention, incidence of subcutaneous fat necrosis, incidence of acute kidney injury, mortality'}], 'secondaryOutcomes': [{'measure': 'Number of patients with cutaneous injury', 'timeFrame': '24 hours', 'description': 'New-onset of skin breakdown, bruising, ecchymosis or petechiae, within 24 hours after the end of the maneuver (comparing to the previous baseline assessment)'}, {'measure': 'Number of patients with transient and persistent pain defined as a premature infant pain profile (PIPP) score >7', 'timeFrame': '24 hours', 'description': 'Pain measured by PIPP score \\> 7 will be considered as an episode of pain. A patient will be considered to have persistent pain if PIPP score is higher than the baseline score 6 hours after the maneuver.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hypoxic-Ischemic Encephalopathy'], 'conditions': ['Hypoxic-Ischemic Encephalopathy']}, 'descriptionModule': {'briefSummary': 'Remote Ischemic Conditioning has never been studied in neonates with HIE. However, RIC has been studied in animal models of perinatal asphyxia and has shown encouraging results. In neonatal rats with HIE, RIC is associated with reduced sensory motor deficits compared to non-RIC, and repeated cycles in three consecutive days is superior to a single treatment. In piglets, four cycles of 10 minutes of bilateral hindlimb ischemia immediately after bilateral common carotid occlusion results in reduced cell death in the periventricular white matter and internal capsule. These preclinical studies support the hypothesis that RIC may be beneficial in infants with HIE.', 'detailedDescription': 'Hypoxic-ischemic encephalopathy (HIE) is a devastating condition in which newborn infants are deprived of oxygen in the peripartum period, resulting in brain injury. HIE is a leading cause of infant morbidity and mortality worldwide. Within the last 15 years, the introduction of hypothermia as a therapy for HIE has revolutionized our care of these vulnerable infants, but despite these improvements, nearly 50% of infants die or have major disability at 18 months. Therefore, there is a significant need to develop novel adjunctive therapies for HIE.\n\nRemote ischemic conditioning (RIC) is a procedure that involves the application of brief cycles of non-lethal ischemia and reperfusion to a remote site, with the goal of protecting distant organs exposed to ischemic injury. RIC has been extensively studied in experimental models and applied clinically in adults, children, and neonates. In neonates, there have been trials exploring its potential role before cardiac surgery and necrotizing enterocolitis. Most of these studies performed up to 4 cycles of 5 minutes of ischemia in a single day and found RIC to be feasible and safe. Experimental studies suggest that RIC, acting through three inter-related mechanisms (neural, humoral, and systemic pathways) is associated with increased cerebral blood flow, decreased inflammation, and enhanced cell survival. RIC has been studied as a potential treatment in adult stroke, and while the evidence to date is inconclusive, preliminary data suggest that RIC may reduce the size and the severity of the stroke lesion, as well as improve cognitive outcomes.\n\nRIC has been studied in animal models of perinatal asphyxia and has shown encouraging results. In neonatal rats with HIE, RIC is associated with reduced sensory motor deficits compared to non-RIC, and repeated cycles in three consecutive days is superior to a single treatment. In piglets, four cycles of 10 minutes of bilateral hindlimb ischemia immediately after bilateral common carotid occlusion results in reduced cell death in the periventricular white matter and internal capsule. These preclinical studies support the hypothesis that RIC may be beneficial in infants with HIE. In this proposal, we outline a carefully designed and conducted early phase study of RIC in neonates with HIE.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Qualifying for therapeutic hypothermia according to the primary care team based on the current SickKids HIE Protocol\n\nExclusion Criteria:\n\n* Gestational age \\<35 weeks\n* Known central nervous system malformations\n* Known chromosomal or genetic anomalies\n* Confirmed or suspected inborn error of metabolism\n* Parental decision for withdrawal of life-sustaining treatment ("comfort care"). If this decision is made after enrollment but before completion of RIC intervention, no further study-related intervention will be performed.\n* Patients requiring significant hemodynamic support (two or more agents for blood pressure support, \\>0.05mcg/kg/min epinephrine infusion, or \\>0.1 mU/kg/min vasopressin) for the four hour period prior to RIC\n* Patients requiring inhaled nitric oxide or fraction of inspired oxygen (FiO2) \\>50% for the four-hour period prior to RIC'}, 'identificationModule': {'nctId': 'NCT05379218', 'briefTitle': 'RIC in HIE: A Safety and Feasibility Trial', 'organization': {'class': 'OTHER', 'fullName': 'The Hospital for Sick Children'}, 'officialTitle': 'Remote Ischemic Conditioning in Hypoxic-Ischemic Encephalopathy: A Safety and Feasibility Trial', 'orgStudyIdInfo': {'id': '1000077295'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention Arm - Remote Ischemic Conditioning', 'description': 'Remote Ischemic Conditioning', 'interventionNames': ['Device: Remote Ischemic Conditioning']}, {'type': 'NO_INTERVENTION', 'label': 'Control Arm - No Remote Ischemic Conditioning', 'description': "No intervention. A blood pressure cuff will be placed on the infant's arm but will not be inflated."}], 'interventions': [{'name': 'Remote Ischemic Conditioning', 'type': 'DEVICE', 'description': 'Patients randomized to the RIC arm, cohorts of 4 consecutive patients will receive escalating therapy:\n\nA. 4 consecutive patients will undergo 4 cycles of 3 minutes ischemia, followed by 5 minutes reperfusion, on Day 1 of therapeutic hypothermia B. Observing no safety events (see below) from patients in group A, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Day 1 of therapeutic hypothermia.\n\nC. Observing no safety events from patients in group B, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Days 1 and 2 of therapeutic hypothermia.\n\nD. Observing no safety events from patients in group C, 4 consecutive patients will undergo 4 cycles of 5 minutes ischemia, followed by 5 minutes reperfusion, on Days 1, 2, and 3 of therapeutic hypothermia.\n\nAll infants will have an extra 1ml of blood collected.', 'armGroupLabels': ['Intervention Arm - Remote Ischemic Conditioning']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5G 1X8', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'The Hospital for Sick Children', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'Brian Kalish, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The Hospital for Sick Children'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The Hospital for Sick Children', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Neonatologist', 'investigatorFullName': 'Brian Kalish', 'investigatorAffiliation': 'The Hospital for Sick Children'}}}}