Pharmacokinetic Properties of Sertraline Before and After Gastric Bypass Surgery

A Prospective, Longitudinal Comparison of the Pharmacokinetic Properties of Sertraline Before and After Roux-en-Y Gastric Bypass

This study is being conducted to evaluate how the body absorbs and processes the medication sertraline (Zoloft®) before compared to how it is absorbed at two time points after gastric bypass surgery. Participants will be asked to take part in this study at three time points: 1) before their bariatric surgery, 2) at three months following the surgery, and 3) twelve months following surgery. This study will enroll approximately 30 participants.

Study Overview

• Status: Completed
• Conditions: Roux en Y Gastric Bypass Surgery
• Intervention / Treatment: Drug: Sertraline

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Neuropsychiatric Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Male or female between 18 and 60 years of age at the time of Informed Consent
• 2. Scheduled to undergo Roux en Y Gastric Bypass Surgery (RYGBP) or in evaluation for surgery prior to scheduling at the investigators' discretion.
• 3. Ability to swallow whole medication tablets and eat solid foods

Exclusion Criteria:

• 1. Those taking any medication at the time of the study which has a known, clinically significant, drug-interaction with sertraline, which may affect participant safety or threaten the validity of the data.
• 2. Hypersensitivity to sertraline or any excipient contained in either the tablet or solution
• 3. Inability to tolerate blood draws
• 4. History of or current bipolar disorder, psychotic disorder, or current major depressive disorder or suicidality, or other psychiatric condition that the investigator feels may put the subject at additional risk by participating in the study
• 5. Alcohol or other substance abuse in the past four weeks or dependence in the past year
• 6. Currently pregnant or lactating or any participant who wants to become pregnant during the study
• 7. Female participant unwilling to use an accepted method of birth control during the study assessment periods.
• 8. Disulfiram or metronidazole at baseline (due to small percentage of alcohol in sertraline solution) or other medication with a similar interaction with a very small amount of alcohol
• 9. Inability or unwillingness to avoid alcohol or grapefruit juice for the required study duration
• 10. Baseline medications which significantly alter gastrointestinal transit time (e.g. oral anticholinergic medications, metoclopramide, erythromycin) and are taken on a routinely scheduled basis. In addition, any such medication cannot be taken in close proximity (minimum of five half-lives of the drug) to the study sertraline administration.
• 11. Medical condition which may increase participant risk with sertraline
• 12. Hepatic insufficiency (Hepatic insufficiency will be defined as any liver enzyme test on a standard hepatic panel of greater than or equal to twice the upper limit of normal, or any other hepatic abnormality identified on physical exam, self-report, or laboratory testing that puts the participant at risk in the opinion of the study physician or physician assistant.)
• 13. History of daily tobacco product use in the past six months
• 14. Participants who have undergone any type of prior surgical procedure for weight loss
• 15. Significant Latex allergy (liquid form has a latex dropper)
• 16. Participant employed by, or who has immediate family employed by NRI
• 17. History of Hepatitis or HIV Infection

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sertraline	Drug: Sertraline; Single dose sertraline 100 mg, tablet and solution; Other Names: Zoloft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sertraline Plasma Concentrations/Area-Under-the-Curve (AUC)	The primary aim of this research is to provide a prospective, longitudinal comparison of pharmacokinetic measures associated with a single-dose of sertraline in RYGBP patients. Comparisons will be based upon sertraline plasma concentrations obtained prior to surgery and repeated at three and 12 months following surgery. A 24+ month post-surgery follow-up to evaluate sertraline tablet AUC will be offered to a subset of study volunteers.	72 hour intervals

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioavailability comparison between sertraline tablet and sertraline liquid	To characterize the relative bioavailability of the tablet formulation of sertraline 100mg as compared to a reference dose of the liquid preparation of sertraline 100mg before and at three and 12 months following RYGBP.	72 hours
Body Composition and Weight	Chanes in body compsition and weight will be correlated with changes observed in sertraline pharmacokinetic parameters and will be considered exploratory.	72 hours
Hepatic Function	To assess the area under the curve (AUC) ratio of N-desmethylsertraline to sertraline as a measure of hepatic function over time.	72 hours
Plasma Protein Concentrations	To assess changes over time in common drug binding plasma proteins in relationship to observed sertraline plasma levels.	72 hours

Collaborators and Investigators

• Sponsor: North Dakota State University
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Kristine J Steffen, Pharm.D., Ph.D., Neuropsychiatric Research Institute

Publications and helpful links

Helpful Links

• Neuropsychiatric Research Institute Website

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 5, 2010

Study Record Updates

• Last Update Posted (Estimate): April 6, 2016
• Last Update Submitted That Met QC Criteria: April 4, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Bariatric Surgery; Pharmacokinetic; Sertraline; Zoloft; Gastric Bypass
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: 1K23DK085066-01 (U.S. NIH Grant/Contract)