Effect of Bariatric Surgery on Bile Acid Homeostasis
Effect of Gastric Bypass, Sleeve Gastrectomy and Duodenal-jejunal Bypass on Bile Acid Homeostasis
The purpose of this study is to evaluate the effect of bariatric surgery in bile acid homeostasis and its interrelationship with the metabolic changes induced by the surgery.
This study contemplates the following hypothesis:
- Bariatric Surgery induce a new study state in bile acid homeostasis with higher bile acid synthesis in association with increased bile acid content.
- The major effects of bariatric surgery on bile acid synthesis and is observed one month after surgery with a progressively decline during the first year of follow-up.
- Gastric bypass increases serum bile acid content, postprandial plasma bile acid response and fecal bile acid excretion.
- Serum bile acids changes induced by gastric bypass are positively correlated with changes in gastric inhibitory polypeptide (GIP) levels and postprandial concentration of insulin and glucagon like peptide-1 (GLP-1) and inversely correlated with thyrotropic hormone (TSH) and postprandial concentration of glucose.
- Changes in postprandial plasma bile acid response induced by gastric bypass positively correlates with changes in postprandial concentration of insulin, GLP-1 and peptide YY (PYY) and inversely correlates postprandial response of ghrelin and glucose.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
The proposed study will be conducted in adult subjects that will undergo to gastric bypass,sleeve gastrectomy or endoscopic duodenal-jejunal bypass.
as treatment for their obesity. As a first approach (Protocol A) in each of these groups the investigators will determine 7α-hydroxy-4-cholestene -3-one (C4) levels, a marker of bile acid synthesis, and fibroblast growth factor 19 (FGF19), inhibitor of the expression of Cholesterol 7- hydroxylase (CYP7A1), prior to surgery and then at months 1, 3, 6 and 12 of postoperative follow-up. The same measurements will be performed to a group of patients under medical treatment when they achieve 10-kg diet-induced weight loss, which is equivalent to one-month of surgically induced weight loss. Preliminary studies suggest that gastric bypass induces a greater weight loss and improvement of associated disease compared with sleeve gastrectomy and endoscopic duodenal-jejunal bypass. Therefore, we expect a deeper change in bile acid homeostasis after gastric bypass, than after the other procedures. For this reason, in patients with gastric bypass the investigators will determine fecal excretion, synthesis, bile acid pool composition, and postprandial plasma response (Protocol B). These variables will be measured prior to surgery and one month after the procedure and also to the group of patients under medical treatment after a 10-kg diet-induced weight loss.
The expression of diverse enzymes, nuclear receptors, transcription factors, transporters as well as cell surface receptors will be quantified at messenger ribonucleic acid (mRNA) and protein level in liver biopsy samples obtained from patients at the time of gastric bypass or sleeve gastrectomy (Protocol C). Those parameters will be reevaluated in liver samples obtained from the same subjects within the first 12 months of the postoperative follow-up.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
-
-
Region Metropolitana
-
Santiago, Region Metropolitana, Chile
- Pontificia Universidad Catolica de Chile
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inclusion Criteria:
- Male and Female, 18 to 50 years old.
- Body mass index(BMI)≥35 and <40 with comorbidities or BMI ≥40 and <45 with or without comorbidities.
- HbA1c<8%.
- Subjects willing to comply with study requirements.
Exclusion Criteria:
- Previous cholecystectomy or gallbladder stones at baseline visit.
- Previous bariatric surgery, small bowel or colon resection.
- Use of drugs:cholestyramine,colesevelam,colestilan, colestimide, colestipol,insulin,exenatide, thiazolidinedione or dipeptidyl peptidase IV(DPPIV)inhibitors, selective serotonin re uptake inhibitor antidepressants.
- Pregnancy or intent to become pregnant.
- Cardiac, renal or liver failure.
- Cancer,infection.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Analysis of hormones and bile acids in patients that have undergone bariatric surgery
Tidsramme: One year
|
One year
|
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Alex G. Escalona, MD, Pontificia Universidad Catolica de Chile
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 11-126
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .