Primary objectives: To examine the effects of: (I) RYGB surgery, (II) obesity and (III) liver fat on drug metabolism using a cocktail approach. Secondary objectives: To examine the effects of: (I) RYGB surgery, (II) obesity and (III) NAFLD, on…
ID
Source
Brief title
Condition
- Other condition
- Hepatic and hepatobiliary disorders
Synonym
Health condition
Obesitas
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study endpoints are the differences in area under the plasma
concentration versus time curve (AUC) for each drug following the
administration of the cocktail in four different situations/ disease states:
(1) early (= anatomical) and (2) late and (3) very late (= weight reduction
dependent) post-RYGB surgery compared to the pre-RYGB surgery situation.
Secondary outcome
Secondary endpoints include the differences in the PK parameters clearance,
volume of distribution, absorption rate, mean residence time and elimination
half-life in the above mentioned situations / disease states.
Background summary
Obesity rates are at an all-time high. This phenomena goes hand in hand with
increasing prevalences of non-alcoholic fatty liver disease (NAFLD) and
Roux-en-Y gastric bypass (RYGB) surgery. Thus far, quality studies
investigating the human pharmacokinetic effects in these disease states are
lacking.
Study objective
Primary objectives: To examine the effects of: (I) RYGB surgery, (II) obesity
and (III) liver fat on drug metabolism using a cocktail approach.
Secondary objectives: To examine the effects of: (I) RYGB surgery, (II) obesity
and (III) NAFLD, on pharmacokinetic parameters, including: clearance, volume of
distribution, absorption rate, mean residence time, and elimination half-life.
Study design
An open-label, single-dose, intervention study.
Study burden and risks
The burden of this study includes a screening visit, five overnight fasts and
four twelve-hour hospital admissions during which the drug cocktail is
administered (five times). For all participants, one urine sample will be
collected to perform an urinary drug screening. Blood samples will be drawn for
pharmacokinetic analysis, monitoring of laboratory parameters and for
pharmacogenetic analysis of liver enzymes. A maximum total volume of 350 ml
blood will be obtained over an one-year period. During the scheduled surgery a
liver biopsy will be taken. Risks associated with this liver biopsy (bleeding
from the biopsy site) will be kept to a minimum by providing several measures
to check for and promote hemostasis. This study will generate information
regarding the drug metabolizing activity in obese with and without NAFLD and
bariatric surgery recipients with an altered gastrointestinal tract.
Information gathered from this study will enhance the ability of medical
professionals to produce recommendations on what changes should be made to
dosing regimen in these disease states; ultimately, reducing medication errors
and thereby drug-associated morbidity and mortality.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
following criteria:
- Capability to provide informed consent and to comply with the requirements
and restrictions listed on the informed consent form;
- Stable weight 3 months prior to inclusion;
- Obese, but otherwise healthy, with the exception of NAFLD, females, aged
between 18 - 45 years;
- Eligible and scheduled for laparoscopic RYGB surgery (in accordance with the
national guidelines (74)).
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Any medical disorder (with the exception of NAFLD and metabolic syndrome);
- Major illness in the past 3 months;
- History of cholecystectomy or other bile duct anomalies;
- (History of) (an) eating disorder(s);
- Use of prescription or non-prescription drugs and herbal or dietary
supplements that affect the CYP enzymes of interest within 30 days prior to the
administration of the drug cocktail, except for oral contraceptives;
- Diabetes;
- Drug abuse or alcoholism (>2 units of alcohol per day);
- Strenuous exercise for at least 3 days prior to each study day, defined as
more than 1 hour of exercise per day;
- Difficulty in donating blood or limited accessibility of a vein;
- Use of tobacco products (induction of liver enzymes).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL65040.018.18 |