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Impact of Body Weight and Weight Loss on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers (COCKTAIL)

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ClinicalTrials.gov Identifier: NCT02386917
Recruitment Status : Active, not recruiting
First Posted : March 12, 2015
Last Update Posted : August 7, 2019
Sponsor:
Collaborators:
University of Oslo
AstraZeneca
Information provided by (Responsible Party):
Jøran Hjelmesæth, The Hospital of Vestfold

Tracking Information
First Submitted Date  ICMJE February 24, 2015
First Posted Date  ICMJE March 12, 2015
Last Update Posted Date August 7, 2019
Study Start Date  ICMJE March 2015
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2017)
  • Bioavailability of drugs (1) [ 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 ]
    Changes in absolute bioavailability (Area Under Curve - oral / Area Under Curve -intravenous) of midazolam after Gastric Bypass and Very Low Calorie Diet, respectively.
  • Bioavailability of drugs (2) [ 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 ]
    Changes in bioavailability (Area Under Curve - oral) of caffeine, losartan, digoxin, rosuvastatin and omeprazole after Gastric Bypass and Very Low Calorie Diet, respectively.
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2015)
  • 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 ]
  • 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 ]
Change History Complete list of historical versions of study NCT02386917 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Body Weight and Weight Loss on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
Official Title  ICMJE Impact of Body Weight, Low Calorie Diet and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Obesity
Intervention  ICMJE
  • Procedure: Gastric bypass
    Weight loss surgery
  • Behavioral: Very low calorie diet
    Non-surgical weight loss procedure
Study Arms  ICMJE
  • Active Comparator: Gastric bypass
    40 patients will undergo gastric bypass
    Intervention: Procedure: Gastric bypass
  • Active Comparator: Very low calorie diet
    40 patients will undergo a very low calorie diet
    Intervention: Behavioral: Very low calorie diet
  • 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.
Publications * Hjelmesæth J, Åsberg A, Andersson S, Sandbu R, Robertsen I, Johnson LK, Angeles PC, Hertel JK, Skovlund E, Heijer M, Ek AL, Krogstad V, Karlsen TI, Christensen H, Andersson TB, Karlsson C. 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). BMJ Open. 2018 May 29;8(5):e021878. doi: 10.1136/bmjopen-2018-021878.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 8, 2015)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02386917
Other Study ID Numbers  ICMJE 2013-2379
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jøran Hjelmesæth, The Hospital of Vestfold
Study Sponsor  ICMJE The Hospital of Vestfold
Collaborators  ICMJE
  • University of Oslo
  • AstraZeneca
Investigators  ICMJE
Principal Investigator: Jøran Hjelmesæth, Professor The Hospital of Vestfold
PRS Account The Hospital of Vestfold
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP