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Pharmacokinetics of Simvastatin Post Laparoscopic Sleeve Gastrectomy (LSG)

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ClinicalTrials.gov Identifier: NCT03571802
Recruitment Status : Unknown
Verified May 2018 by National University Hospital, Singapore.
Recruitment status was:  Not yet recruiting
First Posted : June 28, 2018
Last Update Posted : July 26, 2018
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore

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

Condition or disease Intervention/treatment Phase
Obesity Hyperlipidemias Drug: Simvastatin 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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)
Estimated Study Start Date : September 1, 2018
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

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 Name: Study arm




Primary Outcome Measures :
  1. Area Under Curve (AUC) of simvastatin [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03571802


Contacts
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Contact: Asim Shabbir, MBBS +65 9820 0814 cfsasim@nuhs.edu.sg
Contact: Elaine Lo, PharmD +65 9877 2682 elaine_lo@nuhs.edu.sg

Sponsors and Collaborators
National University Hospital, Singapore
Investigators
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Principal Investigator: Asim Shabbir, MBBS National University Hospital, Singapore
  Study Documents (Full-Text)

Documents provided by National University Hospital, Singapore:
Additional Information:
Publications:
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Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03571802    
Other Study ID Numbers: LSGSIMVASTATIN
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: July 26, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share IPD

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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:
pharmacokinetics
simvastatin
bariatric surgery
laparoscopic sleeve gastrectomy
Additional relevant MeSH terms:
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Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors