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Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

Primary Purpose

Obesity, Morbid, Bariatric Surgery Candidate

Status
Completed
Phase
Not Applicable
Locations
Finland
Study Type
Interventional
Intervention
cocktail of nine CYP probe drugs
Sponsored by
University of Eastern Finland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Obesity, Morbid

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • BMI > 40 kg/m2 or BMI 35-40 kg/m2 and a comorbidity or its risk factor, such as type 2 diabetes, hypertension, sleep apnea, osteoarthritis of weight bearing joints or polycystic ovarian syndrome;
  • previous conservative treatment for obesity had been proven to be ineffective;
  • patients were assigned to undergo LRYGB surgery
  • patients are able to give a written inform consent.

Exclusion Criteria:

  • smokers
  • consuming alcohol more than 20 g per day were included in the study
  • taking drugs which alter CYPs activity
  • history of hypersensitivity to the drugs used in the cocktail

Sites / Locations

  • University of Eastern Finland

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Phenotyping cocktail of 9 CYP probe drugs before surgery

Phenotyping cocktail of 9 CYP probe drugs 1 year after surgery

Arm Description

Outcomes

Primary Outcome Measures

Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB
Probe cocktail drugs concentration-time profile in plasma and urine 1 year after LRYGB

Secondary Outcome Measures

Metabolic ratios of parent compounds and corresponding metabolites before LRYGB
Metabolic ratios of parent compounds and corresponding metabolites 1 year after LRYGB

Full Information

First Posted
June 8, 2018
Last Updated
June 19, 2018
Sponsor
University of Eastern Finland
Collaborators
Diabetes Research Foundation, Finland, Finnish Cultural Foundation, Kuopio University Hospital, Academy of Finland
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1. Study Identification

Unique Protocol Identification Number
NCT03563287
Brief Title
Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs
Official Title
Altered Metabolism of Nutrients and Drugs in Obesity and After Obesity Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
January 27, 2012 (Actual)
Primary Completion Date
December 10, 2014 (Actual)
Study Completion Date
December 10, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Eastern Finland
Collaborators
Diabetes Research Foundation, Finland, Finnish Cultural Foundation, Kuopio University Hospital, Academy of Finland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Due to anatomical and physiological changes caused by the Roux-en-Y gastric bypass (RYGB) bariatric surgery, drug bioavailability after the surgery can be altered. Therefore, post-operative dose adjustment in these patients can be required. The aim of the study was to investigate the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on drug pharmacokinetics and cytochrome P450 (CYP) mediated metabolism using a cocktail of nine CYP probe drugs. The cocktail covers nine main CYP enzymes: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A4). The changes in pharmacokinetic parameters of the drugs as well as modulation of the activity of CYPs are evaluated before and one year after LRYGB. In the study, the patients administering drug cocktail before surgery and 1 year after LRYGB are served as their own controls.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Morbid, Bariatric Surgery Candidate

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phenotyping cocktail of 9 CYP probe drugs before surgery
Arm Type
Experimental
Arm Title
Phenotyping cocktail of 9 CYP probe drugs 1 year after surgery
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
cocktail of nine CYP probe drugs
Intervention Description
Two equally loaded capsules containing: Melatonin (2.0 mg) Nicotine (1.0 mg) Bupropion (37.5 mg) Repaglinide (0.25 mg) Losartan (12.5 mg) Omeprazole (10 mg) Chlorzoxazone (62.5 mg) Midazolam (1.85 mg) Dextromethorphan (30 mg) as an oral solution was administered separately after the capsules.
Primary Outcome Measure Information:
Title
Probe cocktail drugs concentration-time profile in plasma and urine before LRYGB
Time Frame
baseline, 1 hour, 2 hour, 4 hour and 6 hour
Title
Probe cocktail drugs concentration-time profile in plasma and urine 1 year after LRYGB
Time Frame
baseline, 1 hour, 2 hour, 4 hour and 6 hour
Secondary Outcome Measure Information:
Title
Metabolic ratios of parent compounds and corresponding metabolites before LRYGB
Time Frame
baseline, 1 hour, 2 hour, 4 hour and 6 hour
Title
Metabolic ratios of parent compounds and corresponding metabolites 1 year after LRYGB
Time Frame
baseline, 1 hour, 2 hour, 4 hour and 6 hour

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: BMI > 40 kg/m2 or BMI 35-40 kg/m2 and a comorbidity or its risk factor, such as type 2 diabetes, hypertension, sleep apnea, osteoarthritis of weight bearing joints or polycystic ovarian syndrome; previous conservative treatment for obesity had been proven to be ineffective; patients were assigned to undergo LRYGB surgery patients are able to give a written inform consent. Exclusion Criteria: smokers consuming alcohol more than 20 g per day were included in the study taking drugs which alter CYPs activity history of hypersensitivity to the drugs used in the cocktail
Facility Information:
Facility Name
University of Eastern Finland
City
Kuopio
Country
Finland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effects of LRYGB on Pharmacokinetics of Nine CYP Probe Drugs

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