Improving Glucose and Lipid Metabolism Through Caloric Restriction Using Diet or Surgery (CRUDOS)
CRUDOS
Influence of Weight Loss by Diet and Surgery on Metabolomic Profile, Body Composition, and Tissue Specific Glucose Uptake: Insights in Type 2 Diabetes Regression (CRUDOS Study)
1 other identifier
interventional
50
1 country
1
Brief Summary
In this explorative randomized clinical study, the investigators aim to study metabolic, cellular, and molecular changes that occur during weight loss in obese subjects with and without type 2 diabetes. Using novel "imiomics" (imaging technique using PET/MR bioinformatics) analyses to examine possible metabolic differences between energy restricted diet and gastric by-pass surgery on whole-body and tissue specific insulin sensitivity, glucose tolerance, metabolite and protein profiles, fatty acid metabolism, ectopic fat content, and gene expression in adipose tissue. This study aims to identify novel biomarkers and drug targets for type 2 diabetes as well as validate promising and established biomarkers in an interventional model for improved glucose metabolism.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Feb 2016
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 28, 2016
CompletedFirst Submitted
Initial submission to the registry
December 1, 2016
CompletedFirst Posted
Study publicly available on registry
December 9, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2020
CompletedOctober 27, 2017
October 1, 2017
4.3 years
December 1, 2016
October 25, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner
Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.
4 weeks
Metabolite concentrations in plasma
Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry
4 weeks
Gene expression in adipose tissue
Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses
4 weeks
Secondary Outcomes (5)
Lipoprotein changes in plasma assessed by routine clinical chemistry
4 weeks
Plasma adipokines (e.g. adiponectin) assessed by elisa
4 weeks
Fatty acid composition in plasma assessed by gas chromatography
4 weeks
Changes in plasma protein profile (proteomics) assessed by immunohistochemistry
4 weeks
Epigenetic changes assessed as DNA methylation
4 weeks
Study Arms (2)
Gastric by-pass surgery
ACTIVE COMPARATORGastric by-pass surgery without prior low-caloric diet
Low-caloric diet
ACTIVE COMPARATORLow-caloric diet followed by gastric by-pass surgery
Interventions
Gastric by-pass surgery is expected to achieve a mean weight loss of 7-8kg in 4 weeks, which is similar weight-loss achieved in the other arm (low-caloric diet) during this time period.
Energy restricted diet with a total energy intake of 800-1200kcal/day
Eligibility Criteria
You may qualify if:
- Age: 18-60 years
- BMI 35-45
- Sagittal abdominal diameter ≤38.5cm
- For participants with type 2 Diabetes Mellitus, a disease duration of no more than 10 years, treated with 0-3 oral antidiabetic drugs and/or with diet. HbA1C 48-80mmol/mol at baseline visit.
You may not qualify if:
- Diabetes complications: proliferative retinopathy, maculopathy, chronic renal failure stadium 3 with an eGFR\<60, foot ulcers, symptomatic neuropathy
- Medications within 3 months: Insulin, Thiazolidinediones
- Judgment by the investigator that the subject should not participate in the study if considers subject unlikely to comply with study procedures, restrictions and requirements
- Pregnant or planning to be pregnant during the study.
- Known or suspected history of significant drug abuse.
- History of alcohol abuse or excessive intake of alcohol as judged by investigator.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator
- Sleep apnoea
- Any previous serious cardiovascular event, stroke, acute myocardial infarction.
- Any condition when MRI-PET is contraindicated such as, but not limited to, having a pacemaker or claustrophobia
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Uppsala Universitylead
- AstraZenecacollaborator
Study Sites (1)
Uppsala univeristy hospital
Uppsala, 75185, Sweden
Related Publications (1)
Eriksson JW, Pereira MJ, Kagios C, Kvernby S, Lundstrom E, Fanni G, Lundqvist MH, Carlsson BCL, Sundbom M, Tarai S, Lubberink M, Kullberg J, Riserus U, Ahlstrom H. Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI. Diabetologia. 2024 Jul;67(7):1399-1412. doi: 10.1007/s00125-024-06150-3. Epub 2024 Apr 24.
PMID: 38656372DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ulf Riserus, MMed, PhD
Uppsala University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate professor
Study Record Dates
First Submitted
December 1, 2016
First Posted
December 9, 2016
Study Start
February 28, 2016
Primary Completion
June 1, 2020
Study Completion
December 1, 2020
Last Updated
October 27, 2017
Record last verified: 2017-10