Ignite Creation Date:
2025-12-24 @ 9:24 PM
Ignite Modification Date:
2026-03-05 @ 7:52 PM
Study NCT ID:
NCT04465032
Status:
UNKNOWN
Last Update Posted:
2020-07-09
First Post:
2020-01-08
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D065626', 'term': 'Non-alcoholic Fatty Liver Disease'}], 'ancestors': [{'id': 'D005234', 'term': 'Fatty Liver'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069467', 'term': 'Fecal Microbiota Transplantation'}], 'ancestors': [{'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Double-blinded RCT, randomization by Dutch Donor Feces Bank'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Double-blinded randomized controlled trial, randomization 1:1 to allogenic and autologous gut microbiome transplantation'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-12-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-07', 'completionDateStruct': {'date': '2021-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2020-07-07', 'studyFirstSubmitDate': '2020-01-08', 'studyFirstSubmitQcDate': '2020-07-07', 'lastUpdatePostDateStruct': {'date': '2020-07-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-07-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-03-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'the effect on consecutive FMT on liver fat accumulation', 'timeFrame': '12 weeks', 'description': 'measured by MRI Livermultiscan'}], 'secondaryOutcomes': [{'measure': 'alterations in anthropometric data', 'timeFrame': '3, 6 and 12 weeks', 'description': 'differences in weight in kilograms'}, {'measure': 'alterations in anthropometric data', 'timeFrame': '3, 6 and 12 weeks', 'description': 'differences in systolic and diastolic blood pressure in mmHg'}, {'measure': 'alterations in anthropometric data', 'timeFrame': '3, 6 and 12 weeks', 'description': 'differences in waist in centimeters'}, {'measure': 'alterations in pancreatic beta-cell function and insulin resistance', 'timeFrame': '3, 6 and 12 weeks', 'description': 'measured by plasma C-peptide in nmol/L derived during OGTT + arginin'}, {'measure': 'alterations in pancreatic beta-cell function and insulin resistance', 'timeFrame': '3, 6 and 12 weeks', 'description': 'measured by glucose in mmol/L derived during OGTT + arginin'}, {'measure': 'alterations in pancreatic beta-cell function and insulin resistance', 'timeFrame': '3, 6 and 12 weeks', 'description': 'measured by insulin in mU/L derived during OGTT + arginin'}, {'measure': 'alterations in liver enzymes', 'timeFrame': '3, 6 and 12 weeks', 'description': 'Aspartaat aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma glutamyl transpeptidase (GGT), alkalic phosphatase (AF), bilirubin'}, {'measure': 'change in bile composition', 'timeFrame': '3 and 6 weeks', 'description': 'measured using endoscopic bile samples (qualitative measurements)'}, {'measure': 'change in bacterial species in small intestine and feces', 'timeFrame': '3 and 6 weeks', 'description': 'measured by endoscopic duodenal biopsies and fecal samples'}, {'measure': 'changes in lipid homeostasis', 'timeFrame': '3, 6 and 12 weeks', 'description': 'cholesterol, HDL, LDL, triglycerides'}, {'measure': 'alterations in psychological stress', 'timeFrame': '0 and 12 weeks', 'description': 'by measuring cortisol levels in hair samples'}, {'measure': 'alterations in psychological stress', 'timeFrame': 'week 1, week 4, week 7, week 9 during 7 days', 'description': 'by reporting psychological stress daily using stress diaries on a scale from 1-10 (non-validated scale)'}, {'measure': 'alterations in psychological stress', 'timeFrame': '0 and 12 weeks', 'description': 'by Perceived Stres Scale (PSS) questionnaires, scores on a scale from 0-40'}, {'measure': 'changes in physical activity', 'timeFrame': 'during 14 weeks', 'description': 'measuring physical activity by steps with FitBit activity tracker'}, {'measure': 'changes in physical activity', 'timeFrame': 'during 14 weeks', 'description': 'measuring physical activity by active minutes with FitBit activity tracker'}, {'measure': 'changes in physical activity', 'timeFrame': 'during 14 weeks', 'description': 'measuring physical activity by heart rate with FitBit activity tracker'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['NAFLD']}, 'referencesModule': {'references': [{'pmid': '40755230', 'type': 'DERIVED', 'citation': 'Groenewegen B, Ruissen MM, Crossette E, Menon R, Prince AL, Norman JM, Ballieux BEPB, Lamb HJ, Terveer EM, Keller JJ, Tushuizen ME. Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Gut Microbes. 2025 Dec;17(1):2541035. doi: 10.1080/19490976.2025.2541035. Epub 2025 Aug 4.'}]}, 'descriptionModule': {'briefSummary': 'Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The primary objective is to study the effect of consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are weight, waist, blood pressure, metabolic parameters (including glucose, cholesterol, pancreatic beta-cell function, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition and liver enzymes. Stool samples will be collected for microbiota analysis at time point 0, 3, 6 and 12 weeks.', 'detailedDescription': 'Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The investigators hypothesize that altered gut microbiota underlie (hepatic) insulin resistance and liver fat accumulation in NAFLD patients. Fecal microbiota transplantation, through amelioration of gut-microbiota released products like lipopolysaccharides, short-chain fatty acids, alcohol and enzymes, and changes in bile acids, may positively affect NAFLD.\n\nDuring the study 20 patients will be randomized for infusion of allogenic (lean donor) or autologous (own) feces by gastroscopy at time points 0, 3 and 6 weeks on a 1:1 basis. Prior to randomization, and at 12 weeks, all patients will undergo LiverMultiscan to non-invasively quantify liver fat accumulation and other features of NAFLD. In addition, various metabolic parameters (lipids, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition, and liver enzymes will be measured.\n\nThe primary objective is to study the effect on consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are alterations in anthropometrical data (weight, waist, blood pressure), changes in fecal microbiota, liver enzymes, bile composition and metabolic parameters including glucose, lipids, pancreatic beta-cell function and insulin resistance measured as HOMA-IR and objective and subjective stress indicators.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Obese (BMI \\> 27 kg/m2)\n* Males and postmenopausal females\n* Aged 18 to 70 years\n* Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound and/or histological signs of steatosis\n* Written informed consent\n\nExclusion Criteria:\n\n* Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc)\n* Any other liver disease than NAFLD/NASH\n* Present excessive alcohol use defined as \\> 2 units/day\n* Recent use (\\< 3 months) of antibiotics\n* use of possible drugs interfering microbiota or recent (\\< 3 months) changes in dosages\n* use of GLP-1 RA or SU-derivatives\n* Recent (\\< 3 months) weight change (\\>5%)\n* Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history\n* Previous use of glucocorticosteroids, hormonal substitution, pagitaxel, theofyllin, amiodarone, myelosuppresive agents.\n* A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study'}, 'identificationModule': {'nctId': 'NCT04465032', 'acronym': 'NAFTx', 'briefTitle': 'The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD)', 'organization': {'class': 'OTHER', 'fullName': 'Leiden University Medical Center'}, 'officialTitle': 'The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD) - a Randomized-controlled Trial -', 'orgStudyIdInfo': {'id': 'GE17-05'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Autologous gut microbiome transplantation', 'description': 'Three autologous (own) fecal transplantations (at baseline, 3 and 6 weeks)', 'interventionNames': ['Other: Gut microbiome transplantation']}, {'type': 'EXPERIMENTAL', 'label': 'Allogenic gut microbiome transplantation', 'description': 'Three allogenic (lean donor) fecal transplantations (at baseline, 3 and 6 weeks)', 'interventionNames': ['Other: Gut microbiome transplantation']}], 'interventions': [{'name': 'Gut microbiome transplantation', 'type': 'OTHER', 'otherNames': ['Fecal transplantation'], 'description': 'Fecal transplantation will be performed at baseline and at week 3 and 6. At the Department of Clinical Bacteriology either the autologous or allogenic feces is prepared for donation by an experienced lab co-worker. The fecal transplantation will be performed via gastroduodenal endoscopy at the Department of Gastroenterology by an experienced endoscopist. To alleviate the procedure, midazolam is offered to the participants. Following placement of the endoscope in the horizontal duodenum, 150 mL feces solution is inserted via the endoscope.', 'armGroupLabels': ['Allogenic gut microbiome transplantation', 'Autologous gut microbiome transplantation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2333 ZA', 'city': 'Leiden', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Maarten Tushuizen, MD, PhD', 'role': 'CONTACT', 'email': 'm.e.tushuizen@lumc.nl'}, {'name': 'Merel Ruissen, MD', 'role': 'CONTACT', 'email': 'm.m.ruissen@lumc.nl'}], 'facility': 'Leiden University Medical Center', 'geoPoint': {'lat': 52.15833, 'lon': 4.49306}}], 'centralContacts': [{'name': 'Maarten Tushuizen, MD PhD', 'role': 'CONTACT', 'email': 'm.e.tushuizen@lumc.nl', 'phone': '+31 71 5263541'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Leiden University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'Dutch Donor Feces Bank', 'class': 'UNKNOWN'}, {'name': 'Vedanta Biosciences', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principle investigator', 'investigatorFullName': 'metushuizen', 'investigatorAffiliation': 'Leiden University Medical Center'}}}}