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

Sponsor
North Dakota State University (Other)
Overall Status
Terminated
CT.gov ID
NCT02483598
Collaborator
Neuropsychiatric Research Institute, Fargo, North Dakota (Other)
12
Enrollment
2
Arms
36
Duration (Months)

Study Details

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
Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Study Start Date :
Jun 1, 2015
Actual Primary Completion Date :
Jun 1, 2018
Actual Study Completion Date :
Jun 1, 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 [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. [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. [9-18 months following RYGB]

    To compare GLP-2 levels between participants and drug conditions.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Locations

No locations specified.

Sponsors and Collaborators

  • North Dakota State University
  • Neuropsychiatric Research Institute, Fargo, North Dakota

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Kristine Steffen, Associate Professor, North Dakota State University
ClinicalTrials.gov Identifier:
NCT02483598
Other Study ID Numbers:
  • bus-000
First Posted:
Jun 29, 2015
Last Update Posted:
Aug 24, 2018
Last Verified:
Aug 1, 2018
Keywords provided by Kristine Steffen, Associate Professor, North Dakota State University
buspirone
pharmacokinetics
Cytochrome P450 3A4
Additional relevant MeSH terms:
Buspirone

Study Results

No Results Posted as of Aug 24, 2018