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

• ClinicalTrials.gov Identifier: NCT02483598
• Recruitment Status: Terminated
• First Posted: June 29, 2015
• Last Update Posted: August 24, 2018
• Sponsor: North Dakota State University
• Collaborator: Neuropsychiatric Research Institute, Fargo, North Dakota
• Information provided by (Responsible Party): Kristine Steffen, North Dakota State University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gastric Bypass	Drug: Buspirone; Drug: Buspirone and Grapefruit Juice	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Study Start Date: June 2015
• Actual Primary Completion Date: June 2018
• Actual Study Completion Date: June 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Buspirone; Buspirone alone	Drug: Buspirone; 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.; Drug: Buspirone and Grapefruit Juice; Grapefruit juice will be given before and during buspirone administration to inhibit intestinal CYP3A4.
Active Comparator: Buspirone plus grapefruit juice; Buspirone plus grapefruit juice	Drug: Buspirone; 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.; Drug: Buspirone and Grapefruit Juice; Grapefruit juice will be given before and during buspirone administration to inhibit intestinal CYP3A4.

Outcome Measures

Primary Outcome Measures :

1. Area-under-the-curve [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Kristine Steffen, Associate Professor, North Dakota State University
• ClinicalTrials.gov Identifier: NCT02483598 History of Changes
• Other Study ID Numbers: bus-000
• First Posted: June 29, 2015
• Last Update Posted: August 24, 2018
• Last Verified: August 2018

Keywords provided by Kristine Steffen, North Dakota State University:

buspirone; pharmacokinetics; Cytochrome P450 3A4

Additional relevant MeSH terms:

Buspirone; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action