Mechanistic Investigation Of Intestinal Cytochrome p450 3A4 Following Roux-en-Y Surgery And Its Effect on Plasma Concentrations of Buspirone

Phase 4

Terminated

• Conditions: Gastric Bypass
• Interventions: Drug: Buspirone; Drug: Buspirone and Grapefruit Juice

• Registration Number: NCT02483598
• Lead Sponsor: North Dakota State University

Brief Summary

This study is to compare intestinal Cytochrome P450 3A4 (CYP3A4) activity in 9-18 month post weight loss surgery Roux-en-Y Gastric Bypass (RYGB) versus control subjects who have not had a weight loss surgery and are of similar age, gender, body mass index as the gastric bypass group. For this purpose, we will compare post-bariatric surgery patients with control subjects on alterations in systemic exposure of buspirone, a CYP3A4 substrate, when administered with grapefruit juice, a selective intestinal CYP3A4 inhibitor.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-22
• Study First Submitted QC: 2015-06-24
• Study First Posted: 2015-06-29
• Primary Completion: 2018-06
• Study Completion: 2018-06
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-22
• Last Update Posted: 2018-08-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Male or Female
2. Age 18-65 (inclusive, at time of informed consent)
3. No tobacco use in the past three months.
4. Underwent Roux-en-Y Gastric Bypass weight loss surgery 9-18 months prior to study OR has not had a weight loss surgery but matches the gastric bypass patients on age, gender, and BMI.
5. Ability to read, write and understand English.
6. Expresses the ability/willingness to consume grapefruit juice.

Exclusion Criteria

1. Taking a medication that has a clinically significant interaction with buspirone or grapefruit juice or an interaction that may alter the study data.
2. Hypersensitivity to buspirone or any excipient contained within the dosage forms or grapefruit juice.
3. Inability to tolerate repeated blood draws.
4. Any history of bipolar disorder or a psychotic disorder.
5. Current major depressive disorder or current suicidality.
6. Alcohol or substance dependence in the past year.
7. Currently pregnant or lactating or unwillingness to use medically accepted contraception during study.
8. Taking a medication which significantly alters gastrointesinal transit time.
9. Medical conditon which may increase participant risk with buspirone or grapefruit juice.
10. Self reported history of viral hepatits or HIV.
11. Positive urine drug screen unless documented prescription of a non-interacting medication.
12. Renal impairment as evidenced by an estimated glomerular filtration rate (eGFR) of less than or equal to 60 ml/min/1.73 m2 or other abnormality on a renal panel that the medical provider feels puts the participant at risk.
13. Hepatic insufficiency as defined by any hepatic enzyme greater than 3x the upper limit of normal or other hepatic laboratory abnormalities at the discretion of the medical provider.
14. Any contraindication to bioelectrical impedance analysis (BIA) such as pregnancy, the presence of a pacemaker or other implanted mechanical device.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Buspirone	Buspirone and Grapefruit Juice	Buspirone alone
Buspirone plus grapefruit juice	Buspirone and Grapefruit Juice	Buspirone plus grapefruit juice
Buspirone	Buspirone	Buspirone alone
Buspirone plus grapefruit juice	Buspirone	Buspirone plus grapefruit juice

Primary Outcome Measures

Name	Time	Method
Area-under-the-curve	9-18 months following RYGB	The primary aim of this study is to compare the relative difference between the area-under-the-curve (AUC) of buspirone alone (buspirone) with the AUC of buspirone in the presence of grapefruit juice (buspirone + GFJ) in patients who underwent RYGB 9-18 months prior versus a control group of participants who have not undergone bariatric surgery.

Secondary Outcome Measures

Name	Time	Method
Composite of pharmacokinetic measures compared between buspirone and buspirone with grapefruit juice in participants who have undergone RYGB and nonsurgical control participants.	9-18 months following RYGB	General pharmacokinetic comparisons (Cmax, Tmax, half-life, etc.) will be made between the two conditions.
Compare GLP-2 levels between the buspirone and buspirone with grapefruit juice in participants who have undergone RYGB and nonsurgical control participants.	9-18 months following RYGB	To compare GLP-2 levels between participants and drug conditions.