DHB Supplement Interaction Study

NCT02257879 | Withdrawn

• 2 other identifiers: 14020414-E-0204
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Midazolam; CYP3A; Loperamide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (3)

Sequence A

water - GFJ - supplement

Sequence B

GFJ - supplement - water

Sequence C

supplement - water - GFJ

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the Environmental Polymorphisms Registry. Prior to enrollment in this study the participant will be required to enroll in the Environmental Polymorphisms Registry.@@@@@@

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, United States

Location

Related Publications (3)

• 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. doi: 10.1002/jps.20975.

  PMID: 17542018 BACKGROUND

• 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. doi: 10.1517/17425255.3.1.67.

  PMID: 17269895 BACKGROUND

• 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.

  PMID: 21813277 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Shepherd H Schurman, M.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2014
• First Posted: October 7, 2014
• Study Start: October 3, 2014
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: April 24, 2020

Record last verified: 2020-04

Locations

US (1)