Ignite Creation Date:
2025-12-24 @ 7:49 PM
Ignite Modification Date:
2026-03-02 @ 4:11 AM
Study NCT ID:
NCT04410003
Status:
RECRUITING
Last Update Posted:
2024-10-17
First Post:
2020-02-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Metabolic and Metagenomic Effects of Intestinal Microbiome Repopulation in Unexplained Atherosclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D050197', 'term': 'Atherosclerosis'}], 'ancestors': [{'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Patients and persons involved in the followup and assessment of the participants will be blinded to the randomized assignment.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized controlled trial'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-06-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2025-07-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-10-15', 'studyFirstSubmitDate': '2020-02-24', 'studyFirstSubmitQcDate': '2020-05-27', 'lastUpdatePostDateStruct': {'date': '2024-10-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-06-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-07-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes in plasma levels of metabolites of the intestinal microbiome', 'timeFrame': '6 weeks and 12 months', 'description': 'The primary outcome is changes in plasma levels of trimethylamine N-oxide and p-cresylsulfate'}, {'measure': 'Metagenomic changes of the intestinal microbiome', 'timeFrame': '6 weeks and 12 months', 'description': 'Metagenomic changes in the stool of transplant recipients will be analyzed to determine what changes in the intestinal bacteria are associated with changes in the plasma levels of the intestinal metabolites.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Atherosclerosis', 'Intestinal Microbiome']}, 'referencesModule': {'references': [{'pmid': '29702430', 'type': 'BACKGROUND', 'citation': 'Bogiatzi C, Gloor G, Allen-Vercoe E, Reid G, Wong RG, Urquhart BL, Dinculescu V, Ruetz KN, Velenosi TJ, Pignanelli M, Spence JD. Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis. 2018 Jun;273:91-97. doi: 10.1016/j.atherosclerosis.2018.04.015. Epub 2018 Apr 17.'}]}, 'descriptionModule': {'briefSummary': 'Patients with unexplained atherosclerosis (severe atherosclerosis not explained by traditional risk factors) will receive fecal microbial transplants (FMT) from patients with a Protected phenotype (patients who have high levels of risk factors but little or no carotid atherosclerosis). The objective is to determine what changes in the intestinal microbiome are associated with a decline in plasma levels of toxic metabolites of the itnestinal microbiome such as trimethylamine N-oxide (TMAO) and p-cresylsulfate. The intention is to develop an ecosystem therapeutic of cultured bacteria to treat atherosclerosis.', 'detailedDescription': '100 patients with Unexplained Atherosclerosis, and 5 donors with the protected phenotype will be recruited; there will be extensive microbial, viral and parasitic screening of the donors. Recipients will be randomized to receive capsules of stool from the donors, or cellulose placebo. Recipients will take cloxacillin 500 mg 4 times daily for 5 days before the FMT, and will undergo purging with an electrolyte solution, (PegLyte) the day before the FMT. Metagenomic analysis of the recipient stool will be performed before FMT, 6 weeks later and after 12 months.Plasma levels of toxic intestinal metabolites will be measured before FMT, at 6 weeks and 12 months after FMT; the levels to be measured will be TMAO, P-cresylsulfate, Hippuric acid. Indoxyl sulfate, P-cresyl glucuronide. Phenyl acetyl glutamine, and Phenyl sulfate.\n\nThe investigators will analyze the metagenomic changes in the intestinal microbiome of recipients that are associated with decline in the plasma levels of the metabolic products of the intestinal microbiome to identify candidate bacteria for an "ecosystem therapeutic for atherosclerosis. Based on previous experience of designing such a therapeutic for clostridium difficile, it is anticipated that \\~ 40 bacterial species would be needed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Severe atherosclerosis, with total plaque area in the top quartile (\\>119 mm2), not explained by traditional risk factors in linear regression (residual score \\>= 2)\n\nExclusion Criteria:\n\n* Excluded will be patients unwilling/unable to provide informed consent, unwilling to ingest the stool capsules at baseline, patients with moderate to severe renal failure (eGFR\\<50), immunosuppressed patients, and patients with cancer, unstable angina, planned carotid revascularization or other conditions that might be expected to reduce their survival to \\< 1 year (including age \\>80).'}, 'identificationModule': {'nctId': 'NCT04410003', 'briefTitle': 'Metabolic and Metagenomic Effects of Intestinal Microbiome Repopulation in Unexplained Atherosclerosis', 'organization': {'class': 'OTHER', 'fullName': 'Western University, Canada'}, 'officialTitle': 'Metabolic and Metagenomic Effects of Repopulation of the Intestinal Microbiome in Patients with Severe Unexplained Atherosclerosis', 'orgStudyIdInfo': {'id': '115450'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Cellulose capsules, cloxacillin, electrolyte purgative (Peglyte)', 'interventionNames': ['Biological: Fecal microbial transplant']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Active', 'description': 'Capsules of stool from Protected donors, cloxacillin, electrolyte purgative (Peglyte)', 'interventionNames': ['Biological: Fecal microbial transplant']}], 'interventions': [{'name': 'Fecal microbial transplant', 'type': 'BIOLOGICAL', 'description': 'Fecal microbial transplant', 'armGroupLabels': ['Active', 'Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'N6G 2V4', 'city': 'London', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'J. David Spence, M.D.', 'role': 'CONTACT', 'email': 'dspence@robarts.ca', 'phone': '1-519-931-5731'}], 'facility': 'Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}], 'centralContacts': [{'name': 'J. David Spence, M.D.', 'role': 'CONTACT', 'email': 'dspence@robarts.ca', 'phone': '1-519-931-5731'}, {'name': 'Leslie Paddock, R.N.', 'role': 'CONTACT', 'email': 'leslie.paddock@lhsc.on.ca', 'phone': '1-519-931-5731'}], 'overallOfficials': [{'name': 'J. David Spence, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Western University, Canada'}, {'name': 'Chrysi Bogiatzi, M.D.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Division of Neurology, Western University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Data might be made available with approval of the ethics committee'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Western University, Canada', 'class': 'OTHER'}, 'collaborators': [{'name': 'European Bioinformatics Institute', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}