Pharmacokinetics of Simvastatin Post Laparoscopic Sleeve Gastrectomy (LSG)

Sponsor
National University Hospital, Singapore (Other)
Overall Status
Recruiting
CT.gov ID
NCT03571802
Collaborator
(none)
10
1
1
84.6
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Study Details

Study Description

Brief Summary

This study aims to investigate the change in systemic exposure of simvastatin post LSG.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Morbid obesity (Body mass index > 40 kg/m2 or 35-39 kg/m2 with comorbidity; 37.5 kg/m2 for Asians) is a growing global health issue. Bariatric surgery is the only intervention that has demonstrated sustainable reduction in weight and comorbidities.1,2 Among the various bariatric procedures, laparoscopic sleeve gastrectomy (LSG) has rapidly gained popularity worldwide.3,4 Physiological alterations following LSG include reduction in gastrointestinal surface and reduced retention of food. Bioavailability of drugs may be affected but published literature in this area is sparse and studies are usually small and uncontrolled.5-7 Moreover, some reports concerning gastric banding and jejunoileal bypass are no longer practiced because of the associated risk. In general, bioavailability of orally administered drug changes with a reduction in gastrointestinal area. While Kroll et al showed slight increase in area under curve of rivaroxaban post bariatric surgery8, Skottheim et al demonstrated significant but variable change in systemic exposure of atorvastatin after gastric bypass (from threefold decrease to twofold increase) that diminished but was sustained with time (21-45 months post gastric bypass)9-10.

No study has investigated the change in pharmacokinetics of simvastatin post LSG.

Simvastatin is a widely-used lipid-lowering agent with a low bioavailability of 5% due to the extensive first pass metabolism.11 As simvastatin undergoes hydrolysis in the stomach to the active form12, it is postulated that bioavailability of simvastatin will decrease after LSG.13-15 A decrease in bioavailability may be associated with reduced efficacy. Authors of review articles suggested choosing an alternative agent to simvastatin post bariatric surgery. However, such recommendation is largely based on theoretical concern rather than solid evidence.14,15 A previous study attempted to model the pharmacokinetics of simvastatin post Roux-en-Y and biliopancreatic diversion with duodenal switch.13 The data is not applicable to LSG and the model did not take into account of the pH-dependent hydrolysis. This will be the first study aiming to investigate the change in systemic exposure of simvastatin post LSG.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Pharmacokinetic parameters of simvastatin before and after laparoscopic sleeve gastrectomy will be compared in 10 patients. Each patient will serve as their own control for comparison.Pharmacokinetic parameters of simvastatin before and after laparoscopic sleeve gastrectomy will be compared in 10 patients. Each patient will serve as their own control for comparison.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Need of Dosing Adjustment for Simvastatin in Obese Patients Post Bariatric Surgery- Laparoscopic Sleeve Gastrectomy (LSG)
Actual Study Start Date :
Jun 13, 2018
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Jun 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: intervention arm

simvastatin 20mg once

Drug: Simvastatin
The subject will take simvastatin 20mg at 0 h (after stopping simvastatin for 5 days). 5 mL of blood will be sampled at 0 h, 1 h, 2 h, 3 h, 5 h, 7 h. There will be 2 blood sampling sessions: 1 before and the other 3 months after surgery.
Other Names:
  • Study arm
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under Curve (AUC) of simvastatin [baseline (before surgery). 3 months after surgery]

      Ratio of AUC of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    2. Maximum serum concentration (Cmax) of simvastatin [baseline (before surgery). 3 months after surgery]

      Ratio of Cmax of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    3. Time at which maximum serum concentration (Tmax) of simvastatin [baseline (before surgery). 3 months after surgery]

      Ratio of Tmax of simvastatin for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    4. Area Under Curve (AUC) of simvastatin acid [baseline (before surgery). 3 months after surgery]

      Ratio of AUC of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    5. Maximum serum concentration (Cmax) of simvastatin acid [baseline (before surgery). 3 months after surgery]

      Ratio of Cmax of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    6. Time at which maximum serum concentration (Tmax) of simvastatin acid [baseline (before surgery). 3 months after surgery]

      Ratio of Tmax of simvastatin acid for each subject before and 3 months after surgery will be calculated, the mean ratio will be reported

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Planned for laparoscopic sleeve gastrectomy at National University Hospital

    • Taking statin

    • Aged 21 or above

    Exclusion Criteria:
    • Patient on concomitant treatment with medications/ food/ herbal supplements that may affect the pharmacokinetics of simvastatin: boceprevir, conivaptan, cyclosporine, efavirenz, mitotane, tocilizumab, rifamycin, amiodarone, amlodipine, aprepitant, azithromycin, colchicine, fenofibrate, imatinib, raltegravir, ranolazine, teriflunomide, ticagrelor, fusidic acid, protease inhibitors, telaprevir, telithromycin, gemfibrozil, erythromycin, clarithromycin, carbamazepine, rifampicin, ketoconazole, fluconazole, itraconazole, voriconanzole, diltiazem, verapamil, dexamethasone, prednisolone, phenytoin, ritonavir, indinavir, nelfinavir, bosentan, telithromycin, nefazodone, St John's wort, orlistat, sibutramine and other strong CYP 3A4 inhibitors/ inducers

    • Pregnant ladies

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National University Hospital Singapore Singapore 119228

    Sponsors and Collaborators

    • National University Hospital, Singapore

    Investigators

    • Principal Investigator: Asim Shabbir, MBBS, National University Hospital, Singapore

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    National University Hospital, Singapore
    ClinicalTrials.gov Identifier:
    NCT03571802
    Other Study ID Numbers:
    • LSGSIMVASTATIN
    First Posted:
    Jun 28, 2018
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by National University Hospital, Singapore
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 8, 2022