Ignite Creation Date:
2025-12-24 @ 5:54 PM
Ignite Modification Date:
2025-12-27 @ 1:47 PM
Study NCT ID:
NCT06668168
Status:
RECRUITING
Last Update Posted:
2025-07-31
First Post:
2024-10-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Causal Role of Ketone Bodies in Obesity-associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009765', 'term': 'Obesity'}, {'id': 'D050177', 'term': 'Overweight'}], 'ancestors': [{'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D055423', 'term': 'Diet, Ketogenic'}], 'ancestors': [{'id': 'D050528', 'term': 'Diet, Carbohydrate-Restricted'}, {'id': 'D004035', 'term': 'Diet Therapy'}, {'id': 'D044623', 'term': 'Nutrition Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D004032', 'term': 'Diet'}, {'id': 'D009747', 'term': 'Nutritional Physiological Phenomena'}, {'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Outcome assessors will be masked to the group allocation when analysis is outsourced from the University.'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 69}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-05-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2030-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-28', 'studyFirstSubmitDate': '2024-10-30', 'studyFirstSubmitQcDate': '2024-10-30', 'lastUpdatePostDateStruct': {'date': '2025-07-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-10-31', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-05-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Plasma proteome', 'timeFrame': 'From baseline to week 4', 'description': 'Plasma proteome at week 4 adjusted for baseline values'}, {'measure': 'Transcriptome of peripheral blood mononuclear cells', 'timeFrame': 'From baseline to week 4', 'description': 'Transcriptome of peripheral blood mononuclear cells at week 4 adjusting for baseline values'}, {'measure': 'Transcriptome of adipose tissue', 'timeFrame': 'From baseline to week 4', 'description': 'Transcriptome of subcutaneous abdominal adipose tissue at week 4 adjusting for baseline values'}], 'secondaryOutcomes': [{'measure': 'Apolipoprotein B concentrations', 'timeFrame': 'From baseline to week 4', 'description': 'Plasma apolipoprotein B concentrations at week 4 adjusted for baseline values.'}, {'measure': 'Urinary albumin concentrations', 'timeFrame': 'From baseline to week 4', 'description': 'Urinary albumin concentrations at week 4 adjusting for baseline values'}, {'measure': 'Fasting glucose concentrations', 'timeFrame': 'From baseline to week 4', 'description': 'Plasma fasting glucose concentrations at week 4 adjusting for baseline values'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Ketogenic diet'], 'conditions': ['Nutrition', 'Obesity and Overweight']}, 'descriptionModule': {'briefSummary': 'Excess weight increases the risk of several diseases including cardiovascular disease, type 2 diabetes, kidney disease and various cancers. There is a need for preventative strategies for obesity-associated disease, especially for people in the overweight and moderately obese ranges where pharmacological intervention may not be suitable.\n\nLow-carbohydrate (ketogenic) diets are popular for weight control. Ketogenic diets increase circulating ketones, which can have favourable effects on cardiometabolic health markers. However, the ketogenic diet has a nutrient composition associated with harms (high-saturated fat/red meat, and low-fibre). The net effects of ketogenic diets on long-term health are unclear. Ketone supplements can increase circulating ketones and could provide benefits of ketosis without needing to adhere to a potentially harmful diet.\n\nEstablishing causality between complex exposures (e.g., diet) and long-term outcomes (e.g., disease), is challenging. The MRC \\& NIHR Review of Nutrition and Human Health Research (2017) highlighted an "overreliance (as opposed to reasonable reliance) on observational studies" as a key barrier to progression in the field of nutrition and health. Randomised controlled trials (RCTs) facilitate causal inference, but for long-term outcomes are expensive, time-consuming, and often suffer from waning adherence. Mendelian randomization (MR) can estimate causal effects subject to key assumptions. A challenge to these assumptions includes complex behavioural exposures (e.g., diet), which could be intercorrelated with causal factors.\n\nOur proposal will address these limitations with a novel combination of study designs to establish causal effects of ketosis (via diet and supplementation) on obesity-associated disease risk in humans.\n\nThe investigators will combine a tightly controlled, short-term RCT, with MR to link short-term responses to long-term endpoints. The investigators will examine the circulating (blood) and tissue-specific (adipose) transcriptomic and proteomic responses in the fasted and postprandial state in response to our dietary interventions and translate these to MR by identifying single-nucleotide polymorphisms from genome wide association studies. This approach overcomes limitations of RCTs and MR, as adherence to diets will be confirmed with controlled feeding, and intermediate molecular traits as exposure for MR are less likely to be intercorrelated with causal traits.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Body mass index: 25-45 kg/m2\n* Waist circumference \\>93.9 (males) or \\>79.9 (females)\n\nExclusion Criteria:\n\n* Glucose or lipid lowering medication\n* Diagnosis of cardiovascular disease, renal failure, liver disease or type 2 diabetes\n* Contraindications to a ketogenic diet (e.g., pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency)\n* Unable to understand English language'}, 'identificationModule': {'nctId': 'NCT06668168', 'acronym': 'KETO-GENETIC', 'briefTitle': 'The Causal Role of Ketone Bodies in Obesity-associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality', 'organization': {'class': 'OTHER', 'fullName': 'University of Bath'}, 'officialTitle': 'The Causal Role of Ketone Bodies in Obesity-Associated Disease Prevention - Combining Genetic Epidemiology With a Randomised Trial to Infer Causality', 'orgStudyIdInfo': {'id': '23-09665'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'CONTROL'}, {'type': 'ACTIVE_COMPARATOR', 'label': 'KETONE ESTER', 'interventionNames': ['Dietary Supplement: Ketone Monoester (KE)']}, {'type': 'EXPERIMENTAL', 'label': 'KETOGENIC DIET', 'interventionNames': ['Behavioral: Ketogenic diet']}], 'interventions': [{'name': 'Ketone Monoester (KE)', 'type': 'DIETARY_SUPPLEMENT', 'description': '25g ketone ester 3x/day. The ketone ester will be a beta-hydroxybutyrate monoester \\[(R)-3-hydroxybutyl (R)-3-hydroxybutyrate\\].', 'armGroupLabels': ['KETONE ESTER']}, {'name': 'Ketogenic diet', 'type': 'BEHAVIORAL', 'description': 'Ketogenic diet (\\<50 g carbohydrate per day)', 'armGroupLabels': ['KETOGENIC DIET']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'BA2 7AY', 'city': 'Bath', 'state': 'Bath', 'status': 'RECRUITING', 'country': 'United Kingdom', 'contacts': [{'name': 'Javier Gonzalez, PhD', 'role': 'CONTACT', 'email': 'j.t.gonzalez@bath.ac.uk', 'phone': '+441225385518'}], 'facility': 'University of Bath', 'geoPoint': {'lat': 51.3751, 'lon': -2.36172}}], 'centralContacts': [{'name': 'Javier Gonzalez', 'role': 'CONTACT', 'email': 'j.t.gonzalez@bath.ac.uk', 'phone': '+441225385518'}, {'name': 'Sophie L Russell, PhD', 'role': 'CONTACT', 'email': 'slr79@bath.ac.uk', 'phone': '+44 7966 975316'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Bath', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Bristol', 'class': 'OTHER'}, {'name': 'Imperial College London', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Nutrition and Metabolism', 'investigatorFullName': 'Javier Gonzalez', 'investigatorAffiliation': 'University of Bath'}}}}