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

25. oktober 2017 opdateret af: Ulf Risérus, Uppsala University

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.

Studieoversigt

Detaljeret beskrivelse

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).

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

50

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Uppsala, Sverige, 75185
        • Rekruttering
        • Uppsala Univeristy Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 60 år (Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Gastric by-pass surgery
Gastric by-pass surgery without prior low-caloric diet
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.
Aktiv komparator: Low-caloric diet
Low-caloric diet followed by 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.
Energy restricted diet with a total energy intake of 800-1200kcal/day
Andre navne:
  • Energy restricted diet

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in tissue specific glucose uptake measured by euglycemic clamp in PET/MR scanner
Tidsramme: 4 weeks
Tissue specific assessment of glucose metabolism (18FDG uptake) using in-scanner (integrated PET-MR) insulin clamps.
4 weeks
Metabolite concentrations in plasma
Tidsramme: 4 weeks
Plasma metabolite concentrations (metabolomics) are assessed by liquid chromatography-mass spectrometry
4 weeks
Gene expression in adipose tissue
Tidsramme: 4 weeks
Change in gene expression is assessed by microarray (untargeted) messenger ribonucleic acid (mRNA) analyses
4 weeks

Sekundære resultatmål

Resultatmål
Tidsramme
Lipoprotein changes in plasma assessed by routine clinical chemistry
Tidsramme: 4 weeks
4 weeks
Plasma adipokines (e.g. adiponectin) assessed by elisa
Tidsramme: 4 weeks
4 weeks
Fatty acid composition in plasma assessed by gas chromatography
Tidsramme: 4 weeks
4 weeks
Changes in plasma protein profile (proteomics) assessed by immunohistochemistry
Tidsramme: 4 weeks
4 weeks
Epigenetic changes assessed as DNA methylation
Tidsramme: 4 weeks
4 weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Ulf Riserus, MMed, PhD, Uppsala University

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

28. februar 2016

Primær færdiggørelse (Forventet)

1. juni 2020

Studieafslutning (Forventet)

1. december 2020

Datoer for studieregistrering

Først indsendt

1. december 2016

Først indsendt, der opfyldte QC-kriterier

6. december 2016

Først opslået (Skøn)

9. december 2016

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

27. oktober 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. oktober 2017

Sidst verificeret

1. oktober 2017

Mere information

Begreber relateret til denne undersøgelse

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

UBESLUTET

IPD-planbeskrivelse

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.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Kliniske forsøg med Gastric by-pass surgery

3
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