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History of Changes for Study: NCT02386917
Impact of Body Weight and Weight Loss on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers (COCKTAIL)
Latest version (submitted February 9, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 8, 2015 None (earliest Version on record)
2 March 16, 2015 Recruitment Status, Study Status and Contacts/Locations
3 November 20, 2015 Study Status
4 May 2, 2016 Study Status
5 May 5, 2017 Study Status, Outcome Measures, Study Design, IPDSharing and Contacts/Locations
6 January 18, 2018 Recruitment Status, Study Status and Contacts/Locations
7 December 5, 2018 Study Status
8 August 6, 2019 Study Status
9 September 24, 2020 Study Status
10 February 9, 2021 Study Status
Comparison Format:

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Study NCT02386917
Submitted Date:  March 8, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2013-2379
Brief Title: Impact of Body Weight and Weight Loss on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers (COCKTAIL)
Official Title: Impact of Body Weight, Low Calorie Diet and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2015
Overall Status: Not yet recruiting
Study Start: March 2015
Primary Completion: December 2019 [Anticipated]
Study Completion: December 2019 [Anticipated]
First Submitted: February 24, 2015
First Submitted that
Met QC Criteria:
March 8, 2015
First Posted: March 12, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
March 8, 2015
Last Update Posted: March 12, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: The Hospital of Vestfold
Responsible Party: Principal Investigator
Investigator: Jøran Hjelmesæth
Official Title: Professor, Head
Affiliation: The Hospital of Vestfold
Collaborators: University of Oslo
AstraZeneca
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: Drug bioavailability and disposition vary according to body weight and weight loss after bariatric surgery. This study evaluates the impact of body weight and weight loss on the pharmacokinetics of various probe drugs, and compares these effects in three groups of patients receiving either a gall bladder operation, gastric bypass or a very low calorie diet.
Detailed Description:

This study aims to

  1. to investigate the relationship between body composition and the liver/intestine activity and expression of proteins (drug metabolizing enzymes, transporters and regulatory factors) important for drug bioavailability and disposition in the range from normal to morbid obesity (the combined gastric bypass and cholecystectomy groups) at baseline.
  2. to compare the short-term (6-week) and long-term (2 years) effect of gastric bypass (GBP) and a very low calorie diet (VLCD) (matched weight loss) on bioavailability and pharmacokinetics of probe drugs (caffeine, omeprazole, digoxin, midazolam, rosuvastatin, losartan) and biomarkers (and adjoining protein expressions) for cytochrome P450 (CYP)1A2, CYP2C9, CYP2C19, CYP3A, P-glycoprotein (gp) and organic anion-transporting polypeptide (OATP)1B1.
  3. to compare the 3 study groups (GBP, VLCD and cholecystectomy) at baseline with respect to body composition, cardiovascular risk factors and metabolic biomarkers.
  4. to compare the short-term (6-week) changes in glucose metabolism, blood pressure, blood lipids and body composition of matched weight loss and long-term effects (2 year) on body composition, cardiovascular risk factors and metabolic biomarkers, between the GBP and VLCD groups.
Open or close this module Conditions
Conditions: Obesity
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Basic Science
Study Phase: Not Applicable
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 100 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Gastric bypass
40 patients will undergo gastric bypass
Procedure: Gastric bypass
Weight loss surgery
Active Comparator: Very low calorie diet
40 patients will undergo a very low calorie diet
Behavioral: Very low calorie diet
Non-surgical weight loss procedure
No Intervention: Gall bladder operation
20 patients will be asked to undergo one pharmacokinetic study only, and then finish the study. They will not undergo any weight loss intervention.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Changes in absolute bioavailability (Area Under Curve - oral / Area Under Curve -intravenous) of midazolam after Gastric Bypass and Very Low Calorie Diet, respectively.
[ Time Frame: 0 hours and 0.25, 0.5, 1, 1.5, 2, 3, 4, 4.25, 4.5, 5, 5.5, 6, 8, 10*, 12*, 23 and 24 hours following administration ]

2. Changes in bioavailability (Area Under Curve - oral) of caffeine, losartan, digoxin, rosuvastatin and omeprazole after Gastric Bypass and Very Low Calorie Diet, respectively.
[ Time Frame: 0 hours and 0.25, 0.5, 1, 1.5, 2, 3, 4, 4.25, 4.5, 5, 5.5, 6, 8, 10*, 12*, 23 and 24 hours following administration ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Patients scheduled for GBP surgery or VLCD intervention for obesity as well as patients scheduled for cholecystectomy.
  2. BMI ≥ 18.5 kg/m2
  3. Able and willing to donate biopsies (as specified in the protocol) and for the GBP and VLCD patients also willing to perform follow-up 24 hour PK-investigations and other assessments as required by the clinical study protocol
  4. Stable body weight (< 5 kg self reported weight change) during the last 3 months before inclusion.
  5. Signed informed consent.

Exclusion Criteria:

  • Concomitant treatment with drugs (according to available literature, appendix 3) and/or other factors that may influence the cocktail drug pharmacokinetics such as grapefruit juice, Seville oranges, Pomelo juice, St. Johns wort, tobacco and coffee/tea in close approximation to the investigations.
  • Bradyarrhythmia, Wolff-Parkinson-White (WPW)-syndrome, atrioventricular block 2-3.
  • Electrolyte disturbances (particularly hypokalemia or hypomagnesemia).
  • Renal impairment: eGFR < 30 mL/min.
  • Blood donations the last 4 months.
  • Previous bariatric or upper gastrointestinal surgery.
  • Diabetic patients treated with glitazones, insulin or sulfonylureas.
  • Pregnancy (checked with HCG in urine at screening) and breast-feeding mothers.
  • Known hypersensitivity (including allergy) to drugs included in the cocktail and/or local anesthesia.
  • Anticoagulants with associated risk in combination with biopsies.
  • Non-compliance with regards to visits and/or diet.
Open or close this module Contacts/Locations
Central Contact Person: Jøran Hjelmesæth, Professor
Telephone: +4733342000
Email: joran.hjelmeseth@siv.no
Study Officials: Jøran Hjelmesæth, Professor
Principal Investigator
The Hospital of Vestfold
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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