Ignite Creation Date:
2025-12-24 @ 4:55 PM
Ignite Modification Date:
2026-01-18 @ 11:48 PM
Study NCT ID:
NCT05842850
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-12-03
First Post:
2023-04-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D065626', 'term': 'Non-alcoholic Fatty Liver Disease'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D005234', 'term': 'Fatty Liver'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Participants will be recruited from a nested case-control (NAFLD) screening study. Participants will be examined on two separate days at baseline (both groups) and after 4-weeks caloric restriction (LBW with NAFLD only). The caloric restriction intervention will start immediately after completion of baseline examinations. Participants will adhere to a caloric restriction protocol for 4-weeks limiting daily food intake to a window of 8 hours (8am to 4pm) and water-fasting for the remaining hours of the day. Participants will be instructed to eat a balanced diet according to the current dietary guidelines reduced by 20% calories to ensure energy deficit. A weighed food diary and accelerometers will be used for 3-days to estimate baseline dietary intake and physical activity and to monitor intervention adherence after 2 and 4 weeks.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 24}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-02-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-11', 'completionDateStruct': {'date': '2025-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-11-27', 'studyFirstSubmitDate': '2023-04-11', 'studyFirstSubmitQcDate': '2023-04-24', 'lastUpdatePostDateStruct': {'date': '2024-12-03', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-05-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Adipocyte size', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Adipose tissue immunohistochemistry'}, {'measure': 'Collagen content', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Adipose tissue immunohistochemistry'}, {'measure': 'Transcriptomics', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'RNAseq of bulk subcutaneous adipose tissue'}, {'measure': 'Transcriptomics', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'RNAseq of ex vivo cultured preadipocytes'}, {'measure': 'Epigenetics', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Genome-wide DNA methylation of subcutaneous adipose tissue'}, {'measure': 'Epigenetics', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Genome-wide DNA methylation of ex vivo cultured preadipocytes'}, {'measure': 'Metabolism of ex vivo differentiated preadipocytes', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Functional characterization of lipid metabolism'}, {'measure': 'Metabolism of ex vivo differentiated preadipocytes', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Functional characterization of glucose metabolism'}], 'primaryOutcomes': [{'measure': 'Liver fat content', 'timeFrame': 'Change from baseline in liver fat content at 4 weeks', 'description': 'Liver elastography (FibroScan)'}, {'measure': 'Liver fat content', 'timeFrame': 'Change from baseline in liver fat content at 4 weeks', 'description': 'Validation by Magnetic resonance spectroscopy (MRS)'}], 'secondaryOutcomes': [{'measure': 'Liver fibrosis', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Liver elastography (FibroScan)'}, {'measure': 'Whole-body insulin sensitivity', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Stepwise hyperinsulinemic-euglycemic clamp'}, {'measure': 'Beta-cell function', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Intravenous glucose tolerance test'}, {'measure': 'Glucose turnover rate', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Stable isotope dilution technique'}, {'measure': 'Fat turnover rate', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Stable isotope dilution techniques'}, {'measure': 'Urea turnover rate', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Stable isotope dilution techniques'}, {'measure': '24-hour energy metabolism', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'Indirect calorimetry in respiratory chamber'}, {'measure': 'Body composition', 'timeFrame': 'Baseline and after 4 weeks', 'description': 'DEXA scan'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Adipose tissue biology', 'Caloric restriction', 'Insulin resistance', 'Energy expenditure', 'Insulin secretion'], 'conditions': ['NAFLD']}, 'descriptionModule': {'briefSummary': 'The investigators will conduct a proof-of-principle deep phenotyping 4-weeks caloric restriction intervention study in low birth weight (LBW) subjects with NAFLD and normal birth weight (NBW) controls. Furthermore, the investigators will provide extended in-depth mechanistic insight into the role of impaired subcutaneous adipose tissue (SAT) expandability in ectopic fat deposition in LBW subjects in LBW individuals with and without NAFLD.', 'detailedDescription': 'An adverse fetal environment characterized by low birth weight (LBW) plays a key role in the development of type 2 diabetes (T2D). The investigators recently demonstrated a 3-fold increase in liver fat in 26 early middle-aged LBW compared to 22 normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). The investigators hypothesize that ectopic fat deposition and NAFLD is among the earliest disease manifestations and on the critical path to the development of more severe cardiometabolic disease in LBW. The investigators furthermore hypothesize, that LBW individuals exhibit ectopic liver fat due to reduced capacity to store fat in the subcutaneous adipose tissue (SAT) depot, and that early detection and subsequent intensive caloric restriction, in middle-aged LBW individuals with overt NAFLD, may represent a targeted and highly efficient way forward to prevent more severe cardiometabolic disease manifestations in LBW subjects. To further explore the recent findings, the investigators aim to perform an extended nested case-control screening study for NAFLD in 250 early middle-aged non-obese LBW men and women, and subsequently to conduct a deep-phenotyping, proof-of-principle 4 week time-restricted eating (TRE) intervention study in 12 LBW subjects with NAFLD including measures of hepatic fat content, glucose, insulin and lipid metabolism, as well as 24h metabolic profiles using respiratory chambers. Finally, the investigators will provide extended in-depth mechanistic insight into transcriptional, epigenetic as well as functional SAT and preadipocyte perturbations underlying impaired SAT expandability in LBW individuals with and without NAFLD and NBW controls studied before and after different dietary interventions including TRE and high carbohydrate overfeeding.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '35 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* LBW subjects with NAFLD (liver fat content ≥5% liver fat content verified on MRS)\n* Gender- and body mass index-matched NBW controls without NAFLD\n* Born at term (weeks 39-41)\n\nExclusion Criteria:\n\n* BMI\\<18.5 and BMI\\>30 kg/m2\n* Family history of diabetes (siblings, parent, and grandparents)\n* Disease/medication known to affect primary outcome\n* Self-reported high physical activity level\n* Alcohol intake above general recommendations.\n* Metabolic/liver disease\n* Weight gain/loss of \\>3 kg within the past 6 months'}, 'identificationModule': {'nctId': 'NCT05842850', 'briefTitle': 'Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals', 'organization': {'class': 'OTHER', 'fullName': 'Steno Diabetes Center Copenhagen'}, 'officialTitle': 'Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals - Reversibility and Mechanistic Studies.', 'orgStudyIdInfo': {'id': 'NAFLD reversibility'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'LBW individuals with NAFLD', 'description': 'LBW individuals with NAFLD', 'interventionNames': ['Behavioral: Caloric restriction intervention']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'NBW controls without NAFLD', 'description': 'Age-, gender- and body mass index-matched NBW controls without NAFLD', 'interventionNames': ['Other: No intervention']}], 'interventions': [{'name': 'Caloric restriction intervention', 'type': 'BEHAVIORAL', 'otherNames': ['No intervention'], 'description': 'The intervention consist of 4-weeks limiting daily food intake to a window of 8 hours (8am to 4pm) and water-fasting for the remaining hours of the day. Participants (LBW NAFLD individuals only) will be instructed to eat a balanced diet according to the current dietary guidelines reduced by 20% calories to ensure energy deficit.', 'armGroupLabels': ['LBW individuals with NAFLD']}, {'name': 'No intervention', 'type': 'OTHER', 'description': 'No intervention', 'armGroupLabels': ['NBW controls without NAFLD']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Charlotte Brøns, PhD', 'role': 'CONTACT', 'email': 'charlotte.broens.01@regionh.dk', 'phone': '+4526129093'}], 'overallOfficials': [{'name': 'Charlotte Brøns, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Steno Diabetes Center Copenhagen'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Steno Diabetes Center Copenhagen', 'class': 'OTHER'}, 'collaborators': [{'name': 'Aarhus University Hospital', 'class': 'OTHER'}, {'name': 'Lund University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal investigator', 'investigatorFullName': 'Charlotte Brøns', 'investigatorAffiliation': 'Steno Diabetes Center Copenhagen'}}}}