Type2 DiabetesCRUDOSNCT02988011
Improving Glucose and Lipid Metabolism Through Caloric Restriction Using Diet or Surgery (CRUDOS)
A study testing Gastric by-pass surgery and Low-caloric diet in people with Type2 Diabetes and Weight Loss, run by Uppsala University at 1 site in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Type2 Diabetes, Weight Loss, Insulin Sensitivity
- What is being tested?
- Gastric by-pass surgery and Low-caloric diet
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSweden
- Study dates
- 28 Feb 2016to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Uppsala univeristy hospital
Uppsala, 75185
About this study
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)
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.
Read the 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).
- Conditions
- Type2 Diabetes, Weight Loss, Insulin Sensitivity, Metabolism and Nutrition Disorder, Metabolism Disorder, Glucose, Bariatric Surgery Candidate
- Being tested
- Gastric by-pass surgery, Low-caloric diet
- Keywords
- type 2 diabetes, gastric by-pass surgery, low calorie diet, glucose metabolism
- Medical subject headings
- Weight Loss, Insulin Resistance, Nutrition Disorders, Glucose Metabolism Disorders, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gastric by-pass surgeryProcedure or 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.
Low-caloric dietDietary supplement
Also called Energy restricted diet
Energy restricted diet with a total energy intake of 800-1200kcal/day
| Study group | Role | What they receive |
|---|---|---|
| Gastric by-pass surgery | Active comparator | Gastric by-pass surgery without prior low-caloric diet Receives: Procedure: Gastric by-pass surgery |
| Low-caloric diet | Active comparator | Low-caloric diet followed by gastric by-pass surgery Receives: Procedure: Gastric by-pass surgery; Dietary Supplement: Low-caloric diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Metabolite concentrations in plasma
Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry
Measured: 4 weeks
Gene expression in adipose tissue
Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses
Measured: 4 weeks
Secondary outcomes (5)
Lipoprotein changes in plasma assessed by routine clinical chemistry
Measured: 4 weeks
Plasma adipokines (e.g. adiponectin) assessed by elisa
Measured: 4 weeks
Fatty acid composition in plasma assessed by gas chromatography
Measured: 4 weeks
Changes in plasma protein profile (proteomics) assessed by immunohistochemistry
Measured: 4 weeks
Epigenetic changes assessed as DNA methylation
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2016 (estimated)
- Study start28 Feb 2016
- Primary completionJun 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Ulf Risérus, Uppsala University
- Investigators
- Ulf Riserus, MMed, PhD, Principal investigator, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02988011
- Sponsor's protocol ID
- CRUDOS AZSciLife
- Acronym
- CRUDOS
- Status last verified
- Oct 2017
- First submitted
- 1 Dec 2016
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 38656372
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02988011
- Acronym / sponsor ID
- CRUDOS / CRUDOS AZSciLife
- Conditions
- 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
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 28 Feb 2016 (actual)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 9 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gastric by-pass surgery | Active comparator | Procedure: Gastric by-pass surgeryGastric by-pass surgery without prior low-caloric diet |
| Low-caloric diet | Active comparator | Procedure: Gastric by-pass surgery, Dietary Supplement: Low-caloric dietLow-caloric diet followed by gastric by-pass surgery |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gastric by-pass surgeryGastric 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. | Procedure or surgery | Gastric by-pass surgery, Low-caloric diet |
| Low-caloric dietAlso: Energy restricted dietEnergy restricted diet with a total energy intake of 800-1200kcal/day | Dietary supplement | Low-caloric diet |
Primary outcome
Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner
Time frame: 4 weeks
Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.
Metabolite concentrations in plasma
Time frame: 4 weeks
Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry
Gene expression in adipose tissue
Time frame: 4 weeks
Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses
5 secondary outcomes
Lipoprotein changes in plasma assessed by routine clinical chemistry
Time frame: 4 weeks
Plasma adipokines (e.g. adiponectin) assessed by elisa
Time frame: 4 weeks
Fatty acid composition in plasma assessed by gas chromatography
Time frame: 4 weeks
Changes in plasma protein profile (proteomics) assessed by immunohistochemistry
Time frame: 4 weeks
Epigenetic changes assessed as DNA methylation
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Derived from this study: PubMed 38656372Eriksson 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.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulf Riserus, MMed, PhD principal investigator
Uppsala University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gastric by-pass surgery and Low-caloric diet in people with Type2 Diabetes and Weight Loss, run by Uppsala University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Magnus Sundbom, MD, PhD (+46186114616, magnus.sundbom@surgsci.uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02988011, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.