NCT02386917

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for not_applicable obesity

Timeline
31mo left

Started Mar 2015

Longer than P75 for not_applicable obesity

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress81%
Mar 2015Dec 2028

First Submitted

Initial submission to the registry

February 24, 2015

Completed
16 days until next milestone

First Posted

Study publicly available on registry

March 12, 2015

Completed
6 days until next milestone

Study Start

First participant enrolled

March 18, 2015

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2019

Completed
9.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Expected
Last Updated

October 2, 2024

Status Verified

October 1, 2024

Enrollment Period

4.2 years

First QC Date

February 24, 2015

Last Update Submit

October 1, 2024

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

  • Bioavailability of drugs (1)

    Changes in absolute bioavailability (Area Under Curve - oral / Area Under Curve -intravenous) of midazolam after Gastric Bypass and Very Low Calorie Diet, respectively.

    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

  • Bioavailability of drugs (2)

    Changes in bioavailability (Area Under Curve - oral) of caffeine, losartan, digoxin, rosuvastatin and omeprazole after Gastric Bypass and Very Low Calorie Diet, respectively.

    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

Study Arms (3)

Gastric bypass

ACTIVE COMPARATOR

40 patients will undergo gastric bypass

Procedure: Gastric bypass

Very low calorie diet

ACTIVE COMPARATOR

40 patients will undergo a very low calorie diet

Behavioral: Very low calorie diet

Gall bladder operation

NO INTERVENTION

20 patients will be asked to undergo one pharmacokinetic study only, and then finish the study. They will not undergo any weight loss intervention.

Interventions

Gastric bypassPROCEDURE

Weight loss surgery

Gastric bypass
Very low calorie dietBEHAVIORAL

Non-surgical weight loss procedure

Very low calorie diet

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients scheduled for GBP surgery or VLCD intervention for obesity as well as patients scheduled for cholecystectomy.
  • BMI ≥ 18.5 kg/m2
  • 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
  • Signed informed consent.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

HVestfold

Tønsberg, Vestfold, 3103, Norway

Location

Related Publications (4)

  • Karlsson C, Johnson LK, Greasley PJ, Retterstol K, Hedberg J, Hall M, Hawker N, Robertsen I, Havsol J, Hertel JK, Sandbu R, Skovlund E, Olsen T, Christensen H, Jansson-Lofmark R, Andersson S, Asberg A, Hjelmesaeth J. Gastric Bypass vs Diet and Cardiovascular Risk Factors: A Nonrandomized Controlled Trial. JAMA Surg. 2024 Sep 1;159(9):971-980. doi: 10.1001/jamasurg.2024.2162.

    PMID: 38959017DERIVED

  • Kvitne KE, Asberg A, Johnson LK, Wegler C, Hertel JK, Artursson P, Karlsson C, Andersson S, Sandbu R, Skovlund E, Christensen H, Jansson-Lofmark R, Hjelmesaeth J, Robertsen I. Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity. Clin Transl Sci. 2022 Nov;15(11):2685-2696. doi: 10.1111/cts.13394. Epub 2022 Sep 8.

    PMID: 36037309DERIVED

  • Eide Kvitne K, Hole K, Krogstad V, Wollmann BM, Wegler C, Johnson LK, Hertel JK, Artursson P, Karlsson C, Andersson S, Andersson TB, Sandbu R, Hjelmesaeth J, Skovlund E, Christensen H, Jansson-Lofmark R, Asberg A, Molden E, Robertsen I. Correlations between 4beta-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range. Eur J Clin Pharmacol. 2022 Aug;78(8):1289-1299. doi: 10.1007/s00228-022-03336-9. Epub 2022 Jun 1.

    PMID: 35648149DERIVED

  • Hjelmesaeth J, Asberg 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.

    PMID: 29844102DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Gastric Bypass

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatric SurgeryBariatricsObesity ManagementTherapeuticsGastroenterostomyAnastomosis, SurgicalSurgical Procedures, OperativeDigestive System Surgical Procedures

Study Officials

  • Jøran Hjelmesæth, Professor

    The Hospital of Vestfold

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Head

Study Record Dates

First Submitted

February 24, 2015

First Posted

March 12, 2015

Study Start

March 18, 2015

Primary Completion

June 1, 2019

Study Completion (Estimated)

December 1, 2028

Last Updated

October 2, 2024

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will not share

Locations

NO(1)