Back to results

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

Primary Purpose

Type2 Diabetes, Weight Loss, Insulin Sensitivity

Status

Unknown status

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

Gastric by-pass surgery

Low-caloric diet

About this trial

This is an interventional treatment trial for Type2 Diabetes focused on measuring type 2 diabetes, gastric by-pass surgery, low calorie diet, glucose metabolism

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Uppsala univeristy hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Gastric by-pass surgery

Low-caloric diet

Arm Description

Gastric by-pass surgery without prior low-caloric diet

Low-caloric diet followed by gastric by-pass surgery

Outcomes

Primary Outcome Measures

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.

Metabolite concentrations in plasma

Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry

Gene expression in adipose tissue

Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses

Secondary Outcome Measures

Lipoprotein changes in plasma assessed by routine clinical chemistry

Plasma adipokines (e.g. adiponectin) assessed by elisa

Fatty acid composition in plasma assessed by gas chromatography

Changes in plasma protein profile (proteomics) assessed by immunohistochemistry

Epigenetic changes assessed as DNA methylation

Full Information

NCT ID

NCT02988011

First Posted

December 1, 2016

Last Updated

October 25, 2017

Sponsor

Uppsala University

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT02988011

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Unknown status

Study Start Date

February 28, 2016 (Actual)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Uppsala University

Collaborators

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes, Weight Loss, Insulin Sensitivity, Metabolism and Nutrition Disorder, Metabolism Disorder, Glucose, Bariatric Surgery Candidate

Keywords

type 2 diabetes, gastric by-pass surgery, low calorie diet, glucose metabolism

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gastric by-pass surgery

Arm Type

Active Comparator

Arm Description

Gastric by-pass surgery without prior low-caloric diet

Arm Title

Low-caloric diet

Arm Type

Active Comparator

Arm Description

Low-caloric diet followed by gastric by-pass surgery

Intervention Type

Procedure

Intervention Name(s)

Gastric by-pass surgery

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Low-caloric diet

Other Intervention Name(s)

Energy restricted diet

Intervention Description

Energy restricted diet with a total energy intake of 800-1200kcal/day

Primary Outcome Measure Information:

Title

Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner

Description

Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.

Time Frame

4 weeks

Title

Metabolite concentrations in plasma

Description

Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry

Time Frame

4 weeks

Title

Gene expression in adipose tissue

Description

Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Lipoprotein changes in plasma assessed by routine clinical chemistry

Time Frame

4 weeks

Title

Plasma adipokines (e.g. adiponectin) assessed by elisa

Time Frame

4 weeks

Title

Fatty acid composition in plasma assessed by gas chromatography

Time Frame

4 weeks

Title

Changes in plasma protein profile (proteomics) assessed by immunohistochemistry

Time Frame

4 weeks

Title

Epigenetic changes assessed as DNA methylation

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Magnus Sundbom, MD, PhD

Phone

+46186114616

magnus.sundbom@surgsci.uu.se

First Name & Middle Initial & Last Name or Official Title & Degree

Ulf Riserus, PhD

Phone

+46186117971

ulf.riserus@pubcare.uu.se

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ulf Riserus, MMed, PhD

Organizational Affiliation

Uppsala University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Uppsala univeristy hospital

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

Most of the data is planned to be shared after the study has ended, the date for when this will occur however needs to be decided.

Learn more about this trial

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

We'll reach out to this number within 24 hrs