Ignite Creation Date:
2025-12-24 @ 10:40 PM
Ignite Modification Date:
2026-03-03 @ 3:26 PM
Study NCT ID:
NCT03337035
Status:
COMPLETED
Last Update Posted:
2020-03-04
First Post:
2017-10-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Probiotics and Oxytocin Nasal Spray on Social Behaviors of Autism Spectrum Disorder (ASD) Children
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000067877', 'term': 'Autism Spectrum Disorder'}], 'ancestors': [{'id': 'D002659', 'term': 'Child Development Disorders, Pervasive'}, {'id': 'D065886', 'term': 'Neurodevelopmental Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019936', 'term': 'Probiotics'}], 'ancestors': [{'id': 'D019587', 'term': 'Dietary Supplements'}, {'id': 'D005502', 'term': 'Food'}, {'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}, {'id': 'D019602', 'term': 'Food and Beverages'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': 'this study will be double blinded for both participants/guardians and medication administrator'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal OXT + oral placebo, and b. intranasal OXT + oral probiotics'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 35}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-12-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2019-10-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-03', 'studyFirstSubmitDate': '2017-10-31', 'studyFirstSubmitQcDate': '2017-11-07', 'lastUpdatePostDateStruct': {'date': '2020-03-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-11-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-10-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Social Responsiveness Scale (SRS) Edition 2', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).'}, {'measure': 'Aberrant Behavior Checklist (ABC) Edition 2', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all a problem", 1- "the behavior is a problem but slight in degree", 2- "the problem is moderately serious" and 3- "the problem is severe in degree". Based on this sub-scores are calculated and added to get the total score.'}], 'secondaryOutcomes': [{'measure': 'Neuroinflammation and Oxytocin levels', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'neuroendocrine biomarker measured in blood ( Melatonin, Oxytocin, Tumour Necrosis Factor alpha, testosterone and Interleukin 6)'}, {'measure': 'structural MRI', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'The software Freesurfer will be used to calculate volume of brain regions and diffusion parameters (e.g. fractional anisotropy and mean diffusivity) from structural T1 and diffusion tensor images respectively. T-tests will be applied for group comparisons.'}, {'measure': 'Functional MRI (resting state)', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'Correlation analysis will be used to calculate the connectivity across different brain regions. T-tests will be used for group comparisons.'}, {'measure': 'Functional MRI (task based)', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'General linear modeling will be used to calculate brain responses to the tasks. T-tests will be used for group comparisons.'}, {'measure': 'Autonomic indices 1', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'Blood volume pulse'}, {'measure': 'Autonomic indices 2', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'heart rate'}, {'measure': 'Autonomic indices 3', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'peripheral skin temperature'}, {'measure': 'Autonomic indices 4', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'skin electrodermal activity'}, {'measure': 'Autonomic indices 5', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'blood oxygen saturation'}, {'measure': 'Microbiome', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': '16s metagenomic sequencing of the microbiome'}, {'measure': 'Eye tracking and Behavioral task (joint attention)', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'joint attention - Conduct T-tests and calculate P values for total and average fixation values for each area of interest'}, {'measure': 'Eye tracking and behavioral task (emotion response)', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'emotion response - The accuracy and reaction time will be calculated for each time point. Then an ANOVA will be used to compare the results.'}, {'measure': 'Eye tracking and behavioral task (eye behavior)', 'timeFrame': 'change from baseline at 0, 16, and 28 weeks', 'description': 'eye behavior - Conduct T-tests and calculate P values for total and average fixation values for each area of interest'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Probiotics, Oxytocin'], 'conditions': ['Autism Spectrum Disorder']}, 'referencesModule': {'references': [{'pmid': '35941573', 'type': 'DERIVED', 'citation': 'Sherman HT, Liu K, Kwong K, Chan ST, Li AC, Kong XJ. Carbon monoxide (CO) correlates with symptom severity, autoimmunity, and responses to probiotics treatment in a cohort of children with autism spectrum disorder (ASD): a post-hoc analysis of a randomized controlled trial. BMC Psychiatry. 2022 Aug 8;22(1):536. doi: 10.1186/s12888-022-04151-3.'}, {'pmid': '32082606', 'type': 'DERIVED', 'citation': 'Kong XJ, Liu J, Li J, Kwong K, Koh M, Sukijthamapan P, Guo JJ, Sun ZJ, Song Y. Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol. Pilot Feasibility Stud. 2020 Feb 12;6:20. doi: 10.1186/s40814-020-0557-8. eCollection 2020.'}]}, 'descriptionModule': {'briefSummary': 'Because oral probiotics reported to potentially induce endogenous Oxytocin, and Oxytocin has been reported to improve social behaviors, the investigators will conduct a pilot trial to compare the effects of probiotics and Oxytocin on social behavioral changes in ASD children. Additionally, the investigators will check oxytocin levels, and perform brain fMRI in some subjects, in order to determine which treatment is more efficient, sustainable, and practical, and whether both treatments in combination are better than either treatment alone. If the trial is conclusive, the investigators will conduct a trial in large scale to understand more the mechanism of ASD behaviors and corresponding effective interventions.', 'detailedDescription': 'This study description is in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines that are published for the evaluation of randomized controlled trials. This clinical trial is a randomized, double-blind placebo controlled study. Subjects will be randomized to 2 groups:\n\nPhase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal Oxytocin(OXT) + oral placebo, and b. intranasal OXT + oral probiotics\n\nThe treatment will proceed for a total of 28 weeks. In the first phase (16 weeks), all the patients will be randomly and proportionally divided into two groups: Group A (30 subjects) receives oral probiotics while Group B (30 subjects) receives an oral placebo. In the second phase, subjects in Group A and Group B will continue their respective oral probiotics or placebo administration as in Phase 1. In addition, both groups will be simultaneously administered with intranasal OXT spray.\n\nTesting will be performed 3 times total (before, during, and after treatment). The tests include behavioral surveys, cognitive tests, clinical autonomic tests, and blood tests for oxytocin levels. Investigators plan to select up to 10 subjects from each group to conduct a series of MRI studies at week 0, week 16 and week 28.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '25 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age between 3-25years old;\n2. Pre-existing diagnosis of autism; subjects may be asked to provide documentation confirming diagnosis by DSM-V-TR criteria, ADOS, ADI-R, or other clinical forms\n3. A care provider who can reliably bring the participant to study visits;\n4. No planned changes in medications or psychosocial interventions during trial (stable medications within the last 2 weeks);\n5. Willingness to provide blood samples\n\nExclusion Criteria:\n\n1. Pregnant woman (before or during the study).\n2. Comorbidity of other neurological and/or psychiatric disorders such as unstable seizures, schizophrenia, schizoaffective disorder, bipolar disorders or history of substance abuse.\n3. Psychotropic medication use\n4. Subjects with active cardiovascular disease that is not controlled by medication.\n5. Oxytocin, antibiotic, or probiotic use within the last 30 days.\n6. Regular nasal obstruction or nosebleeds\n7. Significant hearing, vision, or motor impairments\n8. Habitual consumption of large volumes of water\n9. Started taking new medications within the last 2 weeks'}, 'identificationModule': {'nctId': 'NCT03337035', 'briefTitle': 'Probiotics and Oxytocin Nasal Spray on Social Behaviors of Autism Spectrum Disorder (ASD) Children', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'officialTitle': 'The Effects of Probiotics and Oxytocin Nasal Spray on Social Behaviors of ASD Children- A Pilot Study', 'orgStudyIdInfo': {'id': '2017P001667'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'oral probiotics and oxytocin spray', 'description': 'Subjects will receive oral probiotics, 2 pills per day, for 28 weeks. For the last 12 weeks, subjects will also receive intranasal oxytocin spray at the following dose: 4 IU in week 1, 8 IU in week 2, 16 IU in week 3, and 24 IU in weeks 4-12.', 'interventionNames': ['Drug: intranasal oxytocin', 'Dietary Supplement: oral probiotics']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'oral placebo and oxytocin spray', 'description': 'Subjects will receive oral placebo, 2 pills per day, for 28 weeks. For the last 12 weeks, subjects will also receive intranasal oxytocin spray at the following dose: 4 IU in week 1, 8 IU in week 2, 16 IU in week 3, and 24 IU in weeks 4-12.', 'interventionNames': ['Drug: intranasal oxytocin', 'Dietary Supplement: oral placebo']}], 'interventions': [{'name': 'intranasal oxytocin', 'type': 'DRUG', 'otherNames': ['Novartis Syntocinon'], 'description': '4-24 IU per day, dosage gradually increases', 'armGroupLabels': ['oral placebo and oxytocin spray', 'oral probiotics and oxytocin spray']}, {'name': 'oral probiotics', 'type': 'DIETARY_SUPPLEMENT', 'description': '200 million cfu per day', 'armGroupLabels': ['oral probiotics and oxytocin spray']}, {'name': 'oral placebo', 'type': 'DIETARY_SUPPLEMENT', 'description': '2 pills per day', 'armGroupLabels': ['oral placebo and oxytocin spray']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02129', 'city': 'Charlestown', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.37787, 'lon': -71.062}}], 'overallOfficials': [{'name': 'Xue-Jun Kong, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'There is no plan to share data with researchers not involved in this study.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Research Investigator', 'investigatorFullName': 'Xuejun Kong,MD', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}