Clinical trial NCT06460896: Analysis of the Influence of Gastric By-Pass on the Pharmacokinetics of Common Drugs
Official title: Analysis of the Influence of Gastric By-Pass on the Pharmacokinetics of Common Drugs
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bypass Bariatric Surgery
Keywords: bypass bariatric surgery, metabolic syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-06-14
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Lack of knowledge of digestive absorption of drugs used in metabolic syndrome (MS) before and after gastric by-pass (GBP) in obese patients. The main objective is to study the changes in apparent clearance of candesartan, amlodipine, metformin and rosuvastatin, used in the treatment of metabolic syndrome in obese patients, between the preoperative period and 1 and 6 months after the performance of a GBP.

Detailed description: The aim of this study is to investigate the pharmacokinetics of some of the most frequently prescribed oral drugs in hospital and outpatient medicine, in patients undergoing GBP surgery for obesity associated with metabolic syndrome. Paradoxically, despite their frequency of use, very few data, contradictory data or no data at all characterize the molecules we wish to study.

The number of patients undergoing GBP surgery is growing rapidly, as their life expectancy reaches that of the general population once their weight has normalized. However, while weight loss induced by surgery can improve, and more rarely cure, the comorbidities associated with metabolic syndrome, the majority of patients will need to continue or modify their treatments.

It is therefore essential to know the pharmacokinetics of the antihypertensive, lipid-lowering and hypoglycemic drugs they will be taking throughout their lives, in order to adapt their dosage if necessary, or even to change therapeutic class if their absorption is insufficient after GBP.

Moreover, as some studies have shown, the pharmacokinetics of many molecules are likely to vary over time in these patients (19), probably as a result of weight loss itself, but also possibly due to adaptive phenomena in the digestive tract. Studying the pharmacokinetics of the molecules used in the usual treatment of metabolic syndrome in most obese patients should make it possible to: target the preferred sites of absorption in the digestive tract of the molecules studied, study the variations in absorption linked to GBP but also the pharmacokinetic changes linked to weight loss as a function of time. In fact, metabolic capacity may be both decreased and increased in obese patients compared to healthy subjects (20,21), so that drug clearance may both increase and decrease after weight normalization. It is therefore difficult to predict the pharmacokinetics of drugs immediately or long after GYP. The results obtained should make it possible to adapt treatment in these patients, both in terms of changing the dosage administered and in the choice of molecules.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patients having undergone a complete bariatric course, eligible for bariatric surgery after validation of the operative indication by a multidisciplinary RCP dedicated to obesity, in accordance with HAS criteria: morbid obesity with BMI \> 40 kg/m2 or severe obesity with BMI \>35Kg/m2
* Patients with a comorbidity linked to one of the elements of metabolic syndrome that can be improved by surgery: type 2 diabetes, hypertension, dyslipidemia.
* Patients treated pre-operatively for at least 2 weeks with one or more of the molecules designed to control metabolic syndrome and selected for our study:

  * Antihypertensive: amlodipine; candesartan,
  * Hypolipidemic: rosuvastatin
  * Hypoglycemic agent: metformin
* Patients scheduled for Y-shaped gastric bypass surgery
* Membership of a social security scheme

Exclusion Criteria:

* History of restrictive bariatric surgery (sleeve)
* History of renal or hepatocellular insufficiency
* Patient undergoing treatment or having stopped treatment within the last month with a drug that may alter the clearance of the molecules studied: enzyme inducer or inhibitor (boosted antiproteases, macrolides, azole antifungals, grapefruit juice, rifampicin, rifabutin, phenobarbital, phenytoin, St John's wort), probenecid, non-steroidal anti-inflammatory drugs, etc.
* Patients treated with a drug that may alter the bioavailability of associated drugs: antacids containing aluminium or magnesium hydroxide, gastric dressings, etc.
* Patients for whom it is impossible to give informed consent (language barrier)
* Patients taking part in another interventional clinical study
* Patients under legal protection (guardianship, curatorship)
* Pregnant or breast-feeding women

Primary outcomes:
measure: The main objective is to study the changes in apparent clearance of candesartan, amlodipine, metformin and rosuvastatin, used in the treatment of metabolic syndrome in obese patients
timeFrame: preoperative and postoperative phases at 1 month after surgery
Secondary outcomes:
measure: Determine changes in apparent clearance at 6 months after gastric bypass surgery compared with the pre-operative phase
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Explain changes in apparent clearance as a function of weight loss
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Explain changes in apparent clearance as a function of changes in the fat/lean mass ratio
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Determine changes in apparent volumes of distribution between the pre-operative phase and 1 and 6 months after surgery
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Explain changes in apparent volumes of distribution as a function of body weight loss
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Explain changes in apparent volumes of distribution as changes in body fat
timeFrame: pre-operative phase and 1 and 6 months after surgery
measure: Based on the results obtained, recommend any necessary changes in dosage or therapeutic class for these molecules
timeFrame: pre-operative phase and 1 and 6 months after surgery
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Service de chirurgie digestive, bariatrique et endocrinienne
Study officials:
affiliation: Assistance Publique de Paris
name: Andrea LAZZATI
role: PRINCIPAL_INVESTIGATOR
References: