DHB Supplement Interaction Study

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

Status Withdrawn

Clinical Trial Summary

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.

Clinical Trial Description

6 ,7 -dihydroxybergamottin (DHB) is one of the components of grapefruit juice and is a known irreversible inhibitor of intestinal cytochrome P450 3A (CYP3A). A single serving (240 mL) of grapefruit juice (GFJ) contains less than or equal to 5 mg of DHB. The pharmacokinetic boosting effect of GFJ has fueled the marketing of dietary supplements labeled to contain DHB e.g. DHB 300 (TM) and Trisorbagen that enhance absorption naturally, While these supplements have been found to inhibit CYP3A activity, the DHB content in these supplements is much lower than that, of GFJ. Moreover, the effects of such supplements on the pharmacokinetics of CYP3A-metabolized drugs are largely unknown. This single-center, open-label, randomized, 3-period, single-dose, crossover study in healthy volunteers will compare the drug interaction risk of a dietary supplement known to affect CYP3A with GFJ. The primary objective of this study is to compare the effects of a supplement known to affect CYP3A (e.g.Trisorbagen) with those of GFJ and water on the pharmacokinetics of two model substrates, the FDA-recommended CYP3A probe substrate midazolam, and the dual CYP3A/P-glycoprotein (P-gp) substrate loperamide. This dual-probe substrate approach to assess drug interaction risk will provide mechanistic insight into any interaction observed. Eligible volunteers (n=12) will undergo 3 phases, each comprising an exposure visit and 4 subsequent post-exposure visits to collect blood and urine over 72 or 12 hours, respectively. Exposure visits will be scheduled at least 2 weeks apart to allow washout between the phases. At each exposure visit, participants will be administered oral doses of midazolam hydrochloride (2.5 mg) and loperamide (16 mg) concomitantly with water (240 mL), GFJ (240 mL), or Trisorbagen (with 240 mL water) according to a randomized treatment sequence. Blood and urine will be collected pre-dose and post-dose over 72 (blood) or 12 (urine) hours for subsequent analyses of relevant pharmacokinetic outcomes of each probe substrate, including the primary endpoints area under the concentration-time curve from time zero (pre-dose) to infinity (AUC0-inf) and maximum observed concentration (Cmax). Secondary endpoints include geometric means, estimates of treatment differences, within-subject and between-subject treatment variance, as well as the 95% confidence intervals around those estimates. ;

Related Conditions & MeSH terms

• Healthy Volunteers

• NCT number: NCT02257879
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Start date: October 3, 2014
• Completion date: April 20, 2020