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Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL).
- Source :
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BMJ open [BMJ Open] 2018 May 29; Vol. 8 (5), pp. e021878. Date of Electronic Publication: 2018 May 29. - Publication Year :
- 2018
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Abstract
- Introduction: Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups.<br />Methods and Analysis: This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUC <subscript>oral</subscript> /AUC <subscript>iv</subscript> ) of midazolam (CYP3A4 probe), systemic exposure (AUC <subscript>oral</subscript> ) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers.<br />Ethics and Dissemination: The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK sørøst A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.<br />Trial Registration Number: NCT02386917.<br />Competing Interests: Competing interests: JH, AÅ, RS, LKJ, JKH, ES, VK, T-IK and HC receive no personal financial benefits from the trial. PCA has received a PhD grant, and IR has received a postdoctoral grant from the study budget. CK, TBA, A-LE, MH and SA are employed by AstraZeneca, and CK, A-LE and MH own shares in AstraZeneca.<br /> (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Subjects :
- Biological Availability
Body Composition
Clinical Trials as Topic
Female
Gastric Bypass methods
Humans
Linear Models
Male
Norway
Pharmaceutical Preparations
Risk Factors
Tertiary Care Centers
Weight Loss
Biomarkers
Caloric Restriction adverse effects
Cardiovascular Diseases etiology
Gastric Bypass adverse effects
Obesity, Morbid therapy
Pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 2044-6055
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- BMJ open
- Publication Type :
- Academic Journal
- Accession number :
- 29844102
- Full Text :
- https://doi.org/10.1136/bmjopen-2018-021878