Healthy Volunteers Clinical Trial
Official title:
A Pharmacokinetic Study to Assess and Compare the Drug Interaction Risk of the Grapefruit Juice and Dietary Supplements Known to Inhibit CYP3A Enzyme Activity
Verified date | April 2020 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
Background:
- Drinking grapefruit juice changes how long it takes some medicines to be broken down in the
body. Researchers have found that a substance in grapefruit juice called DHB contributes to
this effect. Some dietary supplements contain DHB and claim to increase the absorption of any
and all supplements, medicine or any other drug. But these usually contain a lot more DHB
than a glass of grapefruit juice. Researchers want to study the effects of grapefruit juice
and supplements with DHB.
Objective:
- To compare how a certain dietary supplement (sold as DHB-300 ) versus grapefruit juice
affects how long it takes a person s body to break down medicines.
Eligibility:
- Healthy volunteers ages 18 - 60.
Design:
- Participants will be screened with medical history, physical exam, and blood and urine
tests.
- Participants will have 3 treatment visits. Participants cannot drive themselves home
from the visits. Each visit lasts about 13.5 hours and includes:
- Questions about medications and participant s health.
- Vital signs taken.
- A finger probe to measure oxygen.
- Blood and urine sampling throughout the visit.
- An IV line inserted into an arm vein. It will stay there throughout the visit.
- Study treatments:
- Midazolam hydrochloride a syrup given to make people sleepy.
- Loperamide a tablet for treating diarrhea.
- 1 glass of water, 1 glass of grapefruit juice, or 1 pill of DHB-300. A different one
will be given at each treatment visit.
- One week before each visit, participants cannot have certain fruits and juices. They
must fast the night before each visit.
- For the 3 days after each visit, participants will return to the clinic 4 times. Their
vital signs will be checked and blood will be drawn.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | April 20, 2020 |
Est. primary completion date | April 20, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
- INCLUSION CRITERIA: - Age 18-60 - Men and non-pregnant women - Participant in the Environmental Polymorphisms Registry. Prior to enrollment in this study the participant will be required to enroll in the -Environmental Polymorphisms Registry. - Willing to abstain from fruit juices, star fruit, grapefruit and grapefruit-related fruits (e.g., pomelo, Seville orange), and grapefruitcontaining products for 1 week prior to Exposure Visits and for the 4 follow-up visits. - Willing to fast (with the exception of water) from midnight prior to the screening visit and each Exposure Visit, including abstaining from alcohol and caffeinated beverages -Ability to successfully complete treatment visits, including securing transportation EXCLUSION CRITERIA: - Women who are currently pregnant or breastfeeding - Current use of known CYP3A inhibitors or inducers, which in the opinion of the Investigator poses an unacceptable risk to the patient or to the validity of study results. Candidates will be asked about medication use during the screening process and on the day of the exposure visits. The collected data will be reviewed by the PI or designee to confirm the candidates eligibility. - Known liver dysfunction or disease as defined by: - ALT - higher than the normative value and/or determined abnormal by the PI - AST higher than the normative value and/or determined abnormal by the PI - ALP higher than the normative value and/or determined abnormal by the PI Known kidney dysfunction or disease or: - Estimated Glomerular Filtration Rate (eGFR)- <60 ml/min per the MDRD equation - Heart disease - Pre-existing and known history of psychiatric disorders - Known history of Myasthenia gravis - Current use of quinidine, ritonavir, and saquinavir (potential interaction with loperamide) - Current use of study drug-related medications (benzodiazepines, opioids, herbal supplements; temporary discontinuation per the investigator s discretion may be allowed). Candidates will be asked about medication use during the screening process and also during each of their exposure visits. The collected data will be reviewed by the PI or designee to confirm the candidates eligibility. - Known allergy or hypersensitivity to any study treatments (i.e., to GFJ, DHB, midazolam, loperamide, green, black or white pepper, and -Indian Gooseberry),any opioids, or benzodiazepines - History of acute-angle glaucoma - History of sleep apnea - Current diagnosis of anemia, as defined by hemoglobin concentration <13 g/dL for males and hemoglobin concentration <11 g/dL for females or hematocrit values (determined by lancet-induced drop of blood from the fingertip or via clinical labs) Hematocrit must be at least 34% for women and 36% for men on every visit. - Blood donation within the past 8 weeks of the exposure visit. - Use of medications for which consumption of GFJ is contraindicated and which in the opinion of the Investigator would pose an unacceptable risk to the patient if discontinued or continued while consuming GFJ. Candidates will be asked about medication use during the screening process. The collected data will be reviewed by the PI or designee to confirm the candidates eligibility. - Any other conditions or substance use that in the opinion of the Investigator would pose an unacceptable risk to the patient or to the validity of the study results. Candidates will be asked about health conditions during the screening process. The collected data will be reviewed by the PI or designee to confirm the candidates eligibility. - BMI >35. |
Country | Name | City | State |
---|---|---|---|
United States | NIEHS Clinical Research Unit (CRU) | Research Triangle Park | North Carolina |
Lead Sponsor | Collaborator |
---|---|
National Institute of Environmental Health Sciences (NIEHS) |
United States,
de Castro WV, Mertens-Talcott S, Derendorf H, Butterweck V. Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J Pharm Sci. 2007 Oct;96(10):2808-17. — View Citation
Lang M, Seifert MH, Wolf KK, Aschenbrenner A, Baumgartner R, Wieber T, Trentinaglia V, Blisse M, Tajima N, Yamashita T, Vitt D, Noda H. Discovery and hit-to-lead optimization of novel allosteric glucokinase activators. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5417-22. doi: 10.1016/j.bmcl.2011.06.128. Epub 2011 Jul 18. — View Citation
Paine MF, Oberlies NH. Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions. Expert Opin Drug Metab Toxicol. 2007 Feb;3(1):67-80. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Pharmacokinetic measures (AUC0 inf, Cmax) of systemic drug exposure | PK measures of systemic probe drug exposure (AUCO-inf and Cmax), determined via conventional non-compartmental methods using Phoenix WinNonlin (v6.2) | AUC from 0-72 h -inf | |
Secondary | Geometric means, estimates of treatment differences, within-subject and between-subject treatment variance, and the 95% confidence intervals around those estimates | AUC from 0-72 h -inf |
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