Improving Glucose and Lipid Metabolism Through Caloric Restriction Using Diet or Surgery (CRUDOS)

Weight Loss Clinical Trial

— CRUDOS  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02988011
• Other study ID #: CRUDOS AZSciLife
• Status: Recruiting
• Phase: N/A
• First received: December 1, 2016
• Last updated: October 25, 2017
• Start date: February 28, 2016
• Est. completion date: December 2020

Study information

• Verified date: October 2017
• Source: Uppsala University
• Contact: Magnus Sundbom, MD, PhD
• Phone: +46186114616
• Email: magnus.sundbom[@]surgsci.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

By using omics platforms such as genomics, proteomics and metabolomics we can have large amount of information about metabolic changes at both tissue and whole body level. In parallel to this, clinical imaging modalities such as Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) have developed rapidly, allowing for whole-body studies of how different tissues are involved in systemic diseases. Furthermore, new hybrid systems such as integrated PET-MRI provide combined information of human morphology and function. The integration of PET with MRI reduces the radiation dose compared with PET-CT to acceptable levels for metabolic studies. To handle the large amounts of data from these examinations we are currently developing an image analysis concept, "Imiomics", that allows holistic analysis of whole-body imaging data with integration of non-imaging data. In the current study, we plan to use PET-MRI as well as imiomics methodology, together with gold standard methodology to assess insulin sensitivity and glucose tolerance in vivo. We aim to conduct a randomized study (CRUDOS study; Caloric Restriction Using Diet Or Surgery) to study glycometabolic effects before and after gastric bypass surgery and low-calorie diet in subjects at different stages of glucose tolerance (i.e. obese subjects with and without T2D).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2020
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Diabetes complications: proliferative retinopathy, maculopathy, chronic renal failure stadium 3 with an eGFR<60, foot ulcers, symptomatic neuropathy

• Medications within 3 months: Insulin, Thiazolidinediones

• Any other condition with in the opinion of the investigator would render the participant unsuitable for inclusion in the study and /or for the patients safety

• 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

Related Conditions & MeSH terms

• Bariatric Surgery Candidate
• Diabetes Mellitus, Type 2
• Disease
• Glucose Metabolism Disorders
• Insulin Resistance
• Insulin Sensitivity
• Metabolic Diseases
• Metabolism and Nutrition Disorder
• Metabolism Disorder, Glucose
• Nutrition Disorders
• Type2 Diabetes
• Weight Loss

Intervention

Procedure:
• Gastric by-pass surgery
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.

Dietary Supplement:
• Low-caloric diet
Energy restricted diet with a total energy intake of 800-1200kcal/day

Locations

Country	Name	City	State
Sweden	Uppsala univeristy hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	AstraZeneca

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Metabolite concentrations in plasma	Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry	4 weeks
Primary	Gene expression in adipose tissue	Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses	4 weeks
Secondary	Lipoprotein changes in plasma assessed by routine clinical chemistry		4 weeks
Secondary	Plasma adipokines (e.g. adiponectin) assessed by elisa		4 weeks
Secondary	Fatty acid composition in plasma assessed by gas chromatography		4 weeks
Secondary	Changes in plasma protein profile (proteomics) assessed by immunohistochemistry		4 weeks
Secondary	Epigenetic changes assessed as DNA methylation		4 weeks