ObesityCOCKTAILNCT02386917
Impact of Body Weight and Weight Loss on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
A study testing Gastric bypass and Very low calorie diet in people with Obesity, run by The Hospital of Vestfold at 1 site in Norway.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Obesity
- What is being tested?
- Gastric bypass and Very low calorie diet
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- 18 Mar 2015to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Stable body weight (< 5 kg self reported weight change) during the last 3 months before inclusion.
- Signed informed consent.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Body Weight, Low Calorie Diet and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
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.
Read the detailed description
This study aims to
- 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.
- 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.
- to compare the 3 study groups (GBP, VLCD and cholecystectomy) at baseline with respect to body composition, cardiovascular risk factors and metabolic biomarkers.
- 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.
- Conditions
- Obesity
- Being tested
- Gastric bypass, Very low calorie diet
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gastric bypassProcedure or surgery
Weight loss surgery
Very low calorie dietBehavioural
Non-surgical weight loss procedure
| Study group | Role | What they receive |
|---|---|---|
| Gastric bypass | Active comparator | 40 patients will undergo gastric bypass Receives: Procedure: Gastric bypass |
| Very low calorie diet | Active comparator | 40 patients will undergo a very low calorie diet Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2015 (estimated)
- Study start18 Mar 2015
- Primary completionJun 2019
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital of Vestfold
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo, AstraZeneca
- Responsible party
- Principal investigator, Jøran Hjelmesæth, The Hospital of Vestfold
- Investigators
- Jøran Hjelmesæth, Professor, Principal investigator, The Hospital of Vestfold
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386917
- Sponsor's protocol ID
- 2013-2379
- Acronym
- COCKTAIL
- Status last verified
- Oct 2024
- First submitted
- 24 Feb 2015
- Last updated
- 2 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 38959017Kvitne 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.
PubMed 36037309Eide 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.
PubMed 35648149Hjelmesaeth 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.
PubMed 29844102
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Body Weight, Low Calorie Diet and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors and Metabolic Biomarkers
- ClinicalTrials.gov ID
- NCT02386917
- Acronym / sponsor ID
- COCKTAIL / 2013-2379
- Conditions
- Obesity
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The Hospital of VestfoldUniversity, hospital or other
- Collaborators
- University of Oslo, AstraZeneca
- Study start
- 18 Mar 2015 (actual)
- Primary completion
- Jun 2019 (actual)
- Study completion
- Dec 2028 (estimated)
- First posted
- 12 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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.
- to compare the 3 study groups (GBP, VLCD and cholecystectomy) at baseline with respect to body composition, cardiovascular risk factors and metabolic biomarkers.
- 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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Gastric bypass | Active comparator | Procedure: Gastric bypass40 patients will undergo gastric bypass |
| Very low calorie diet | Active comparator | Behavioral: Very low calorie diet40 patients will undergo a 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- Stable body weight (< 5 kg self reported weight change) during the last 3 months before inclusion.
- Signed informed consent.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gastric bypassWeight loss surgery | Procedure or surgery | Gastric bypass |
| Very low calorie dietNon-surgical weight loss procedure | Behavioural | Very low calorie diet |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2024.
- Derived from this study: PubMed 38959017Karlsson 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.
- Derived from this study: PubMed 36037309Kvitne 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.
- Derived from this study: PubMed 35648149Eide 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.
- Derived from this study: PubMed 29844102Hjelmesaeth 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jøran Hjelmesæth, Professor principal investigator
The Hospital of Vestfold
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gastric bypass and Very low calorie diet in people with Obesity, run by The Hospital of Vestfold at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02386917, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024; AzTrials last refreshed its copy on 8 Nov 2026.