Ignite Creation Date:
2025-12-24 @ 11:07 PM
Ignite Modification Date:
2025-12-25 @ 8:39 PM
Study NCT ID:
NCT04632069
Status:
COMPLETED
Last Update Posted:
2024-08-29
First Post:
2020-11-12
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
NAC +taVNS in IDM Who Are Poor Oral Feeders
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001068', 'term': 'Feeding and Eating Disorders'}], 'ancestors': [{'id': 'D012817', 'term': 'Signs and Symptoms, Digestive'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000111', 'term': 'Acetylcysteine'}, {'id': 'D055536', 'term': 'Vagus Nerve Stimulation'}], 'ancestors': [{'id': 'D003545', 'term': 'Cysteine'}, {'id': 'D000603', 'term': 'Amino Acids, Sulfur'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D004599', 'term': 'Electric Stimulation Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jenkd@musc.edu', 'phone': '843-792-2112', 'title': 'Dr Dorothea Jenkins', 'organization': 'Medical University of South Carolina'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'small numbers in phase I trial; non concurrent control group'}}, 'adverseEventsModule': {'timeFrame': '36 days', 'description': 'bradycardia defined as heart rate \\<80beats per minute for \\> 5 seconds; emesis', 'eventGroups': [{'id': 'EG000', 'title': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n,g.) 75 or 100mg/kg n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 14 days.\n\nN acetyl cysteine + vagus nerve stimulation: NAC x 14 days, taVNS x 14 days', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 2, 'seriousNumAtRisk': 10, 'deathsNumAffected': 1, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'emesis per day', 'notes': 'emesis after NAC administration with dilution 1:2 with sterile water. no further emesis with dilution 1:3', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'bradycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Daily Oral Feeding Volumes : Difference in Mean Increase', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n,g.) 75 or 100mg/kg n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 14 days.\n\nN acetyl cysteine + vagus nerve stimulation: NAC x 14 days, taVNS x 14 days'}], 'classes': [{'categories': [{'measurements': [{'value': '2.1', 'spread': '0.4', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.009', 'groupIds': ['OG000'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '2.1', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '0.4', 'groupDescription': 'Daily change in po feeding volumes expressed as po ml/kg/d \\[reported as the mean daily change from Day 1 to 18 during NAC/NAC+taVNS minus baseline mean daily change Day -14 to day 0 (before treatment)\\] Null hypothesis: there will be no significant difference in daily change in po feeding volume (ml/kg/d) from baseline to during treatment Power analysis: Estimated +0.2 ml/kg/d before taVNS, and +3ml/kg/d during the 18days of NAC+taVNS treatment, requiring 10 infants with power of 80%, a=0.05.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'repeated measures linear regression: time periods: -14 to Day 0, Day 1-18(independent variable); daily po volumes (Dependent Variable)'}], 'paramType': 'MEAN', 'timeFrame': 'Day -14 to 0, Day 1 to 18', 'description': 'Difference in the Mean daily change in oral feeding volume(reported in in ml/kg/d) from Day 1-18 days of NAC+taVNS treatment minus Days -14 to 0 (baseline)', 'unitOfMeasure': 'ml/kg/day po daily change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'infants of diabetic mothers failing oral feeds in G-tube discussions'}, {'type': 'SECONDARY', 'title': 'Metabolite Concentrations in Basal Ganglia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n,g.) 75 or 100mg/kg n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 14days.\n\nN acetyl cysteine + vagus nerve stimulation: NAC x 14 days, taVNS x 14 days'}], 'classes': [{'categories': [{'measurements': [{'value': '0.13', 'spread': '.08', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.01', 'groupIds': ['OG000'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.13', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '.08', 'estimateComment': 'mean difference between \\[GSH\\] Day 4 of NAC and \\[GSH\\] at baseline', 'groupDescription': "\\[GSH\\] at baseline compared with \\[GSH\\] at day 4 of NAC- by paired t-test in which each participant's \\[GSH\\] is compared at 2 time points Null hypothesis: the \\[GSH\\] in the basal ganglia will be no different after Day 4 of NAC than \\[GSH\\] at baseline Power calculation:With 80% power, alpha of 0.05, we would need 7 patients to show a significant change in basal ganglia \\[GSH\\] of 0.14 +/- 0.13mM from baseline to Day 4 of NAC (paired t-test).", 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'paired t-test'}], 'paramType': 'MEAN', 'timeFrame': 'baseline to 4 days', 'description': 'Change in \\[GSH\\] by MRS from baseline to day 4 of NAC', 'unitOfMeasure': 'mM', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'participants with adequate MRS spectra for analysis'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n.g.) 75mg/kg/dose or 100mg/kg/dose n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 10 days.\n\nN acetyl cysteine + vagus nerve stimulation: NAC x 14 days, taVNS x 10 days'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Recruitment from 8.12.21 to 3.1.23 in the Neonatal intensive care unit of the Medical University of South Carolina'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n,g.) 75mg/kg/dose or 100mg/kg n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 14 days.\n\nN acetyl cysteine + vagus nerve stimulation: NAC x 14 days, taVNS x 14days'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '41.1', 'spread': '1.1', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'age an enrollment', 'unitOfMeasure': 'weeks post menstrual age', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'male/female', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'hispanic or nonhispanic', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'description': 'USA, Charleston, SC', 'unitOfMeasure': 'participants'}, {'title': 'mean daily oral feeding volume of formula or breast milk', 'classes': [{'categories': [{'measurements': [{'value': '47', 'spread': '29', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'mean daily oral feeding volume averaged over 14 days', 'unitOfMeasure': 'ml/kg/day', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-08-10', 'size': 206723, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2024-04-16T13:17', 'hasProtocol': True}, {'date': '2021-11-09', 'size': 1610472, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_000.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2023-03-15T13:11', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Co-investigator analyzing MRI data will be blinded to timing of MRI scan and dose'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'We will obtain parental consent, and then administer NAC 100mg/kg loading dose, followed by 75mg/kg q 6h via nasogastric tube, started 4 days prior to taVNS-paired feeding and continued for a total of 14 days. We will perform pharmacokinetics of oral NAC, and MRIs prior to, after 3-4 days of NAC, and after taVNS treatment period.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-08-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2024-07-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-08-06', 'studyFirstSubmitDate': '2020-11-12', 'resultsFirstSubmitDate': '2024-04-18', 'studyFirstSubmitQcDate': '2020-11-12', 'lastUpdatePostDateStruct': {'date': '2024-08-29', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2024-08-06', 'studyFirstPostDateStruct': {'date': '2020-11-17', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-08-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-03-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Daily Oral Feeding Volumes : Difference in Mean Increase', 'timeFrame': 'Day -14 to 0, Day 1 to 18', 'description': 'Difference in the Mean daily change in oral feeding volume(reported in in ml/kg/d) from Day 1-18 days of NAC+taVNS treatment minus Days -14 to 0 (baseline)'}], 'secondaryOutcomes': [{'measure': 'Metabolite Concentrations in Basal Ganglia', 'timeFrame': 'baseline to 4 days', 'description': 'Change in \\[GSH\\] by MRS from baseline to day 4 of NAC'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'conditions': ['Infant of Diabetic Mother', 'Oxidative Stress', 'Vagus Nerve Stimulation', 'Feeding Disorders']}, 'referencesModule': {'references': [{'pmid': '32256328', 'type': 'BACKGROUND', 'citation': 'Badran BW, Jenkins DD, Cook D, Thompson S, Dancy M, DeVries WH, Mappin G, Summers P, Bikson M, George MS. Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study. Front Hum Neurosci. 2020 Mar 18;14:77. doi: 10.3389/fnhum.2020.00077. eCollection 2020.'}, {'pmid': '30146041', 'type': 'BACKGROUND', 'citation': 'Badran BW, Jenkins DD, DeVries WH, Dancy M, Summers PM, Mappin GM, Bernstein H, Bikson M, Coker-Bolt P, George MS. Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns. Brain Stimul. 2018 Sep-Oct;11(5):1198-1200. doi: 10.1016/j.brs.2018.06.009. Epub 2018 Jun 30. No abstract available.'}]}, 'descriptionModule': {'briefSummary': 'Infants of diabetic mothers who are failing to learn oral feeding by term age equivalence have greater CNS oxidative stress, which interact to predict poor neuroplasticity response to transcutaneous vagus nerve stimulation paired with oral feeding. We propose treating the oxidative stress in IDM infants prior to initiating taVNS, with an FDA-approved antioxidant (N-acetylcysteine, NAC) to improve CNS oxidative stress, which in turn regulates expression of many genes including BDNF, that may enhance motor learning.', 'detailedDescription': 'Our group has recently conducted a first-in-infants pilot trial of pairing transcutaneous auricular vagus nerve stimulation (taVNS) with feeding to assist learning oromotor skills. We are enrolling preterm and HIE infants who are failing to learn oral feeds and clinically determined to need a G-tube. In preliminary data, taVNS paired with one or two daily feedings for 2 weeks resulted in 50% of infants attaining full feeds and avoiding G-tube.\n\nA notable number of non-responders were infants of diabetic mothers (IDM) exposed to poor glucose control during pregnancy, all of whom required a G-tube. Uncontrolled maternal hyperglycemia is associated with increased systemic and neuro-inflammation, CNS oxidative stress, DNA damage, and worse neonatal outcomes compared to infants of euglycemic mothers. In neonatal animal models, hyperglycemia has been shown to decrease BDNF, alter long-term synaptogenesis and hippocampal neurochemistry, with ongoing CNS oxidative stress and inhibition of the cortical neuronal plasticity required for learning. In our pilot trial of taVNS-paired feeding, CNS glutathione concentrations (GSH), a MR spectroscopy (MRS) marker of oxidative stress, had significant interaction with IDM in predicting outcome, strongly suggesting that ongoing CNS oxidative stress contributes to neuropathology in IDMs failing oral feeding.\n\nNAC is an FDA-approved antioxidant that is safe and crosses the blood brain barrier, increasing CNS GSH. NAC reduces CNS oxidative stress, enhances learning and provides a neuroprotective effect after brain injury in our and others neonatal HI and neuroinflammatory animal models. Both GSH and BDNF enhance neuroplasticity. Therefore, we hypothesize that pre-treatment with NAC in IDMs who are failing oral feeding, followed by taVNS-paired feeding, will decrease oxidative stress induced by maternal hyperglycemia and IDM-associated brain injury, and increase response to taVNS-paired feeding rehabilitation.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '5 Months', 'minimumAge': '3 Weeks', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Infants of diabetic mothers who are failing oral feeding, \\>39weeks gestation at enrollment, who are clinically stable, on minimal respiratory support (nasal cannula or room air), and clinical team has determined are G-tube candidates\n\nExclusion Criteria:\n\n* Unstable infants or those requiring positive pressure respiratory support\n* Infants \\<39 weeks gestation at enrollment\n* Major unrepaired congenital anomalies or anomalies that limit feeding volumes\n* Infants with cardiomyopathy\n* Repeated episodes of autonomic instability (apnea/ bradycardia) not self resolving'}, 'identificationModule': {'nctId': 'NCT04632069', 'briefTitle': 'NAC +taVNS in IDM Who Are Poor Oral Feeders', 'organization': {'class': 'OTHER', 'fullName': 'Medical University of South Carolina'}, 'officialTitle': 'N-acetylcysteine Plus Transcutaneous Vagus Nerve Stimulation in Infants of Diabetic Mothers Who Fail Oral Feeding', 'orgStudyIdInfo': {'id': '103800'}, 'secondaryIdInfos': [{'id': 'P20GM109040', 'link': 'https://reporter.nih.gov/quickSearch/P20GM109040', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'NAC + taVNS', 'description': 'NAC will be given via nasogastric tube (n,g.) 100mg/kg loading dose, then 75mg/kg/dose n.g. q 6h, administered 1h before a feed, for a total of 14 days. taVNS will be administered to left ear during active sucking with 2 daily feedings starting after 4 days of NAC, continuing for 10 days.', 'interventionNames': ['Combination Product: N acetyl cysteine + vagus nerve stimulation']}], 'interventions': [{'name': 'N acetyl cysteine + vagus nerve stimulation', 'type': 'COMBINATION_PRODUCT', 'otherNames': ['NAC, Acetadote, taVNS'], 'description': 'NAC x 14 days, taVNS x 10 days', 'armGroupLabels': ['NAC + taVNS']}]}, 'contactsLocationsModule': {'locations': [{'zip': '29425', 'city': 'Charleston', 'state': 'South Carolina', 'country': 'United States', 'facility': 'Medical University of South Carolina', 'geoPoint': {'lat': 32.77632, 'lon': -79.93275}}], 'overallOfficials': [{'name': 'Dorothea Jenkins, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Medical University of South Carolina'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL'], 'timeFrame': 'after publication of results', 'ipdSharing': 'YES', 'description': 'will share de-identified data after publication of results', 'accessCriteria': 'written request of PI'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Medical University of South Carolina', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of General Medical Sciences (NIGMS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Pediatrics', 'investigatorFullName': 'Dorothea D. Jenkins', 'investigatorAffiliation': 'Medical University of South Carolina'}}}}