Trial record 4 of 9 for:    John Wort | NCCAM

Herb-Opioid Interactions

This study has been completed.
Sponsor:
Information provided by:
National Center for Complementary and Alternative Medicine (NCCAM)
ClinicalTrials.gov Identifier:
NCT00027014
First received: November 15, 2001
Last updated: February 7, 2007
Last verified: July 2006
  Purpose

This is a series of studies in healthy volunteers to assess the potential for adverse interactions between St. John's wort (SJW) extract and two narcotic (opioid) pain medications: oxycodone and fentanyl. In the case of oxycodone, we are interested in whether SJW treatment promotes the metabolism of oxycodone, such that it lowers the effectiveness of standard doses of oxycodone in treating pain problems. For the fentanyl study, we will investigate whether SJW treatment will interfere with the delivery of fentanyl to the brain and diminish it's effectiveness to relieve pain. There is evidence to suggest that SJW treatment may increase the activity of a transporter protein, named P-glycoprotein (Pgp), in the blood-brain barrier (BBB) that protects the brain from exposure to drugs and other dietary and environmental toxins.


Condition Intervention Phase
Pain
Drug: St. John's Wort
Drug: oxycodone
Drug: fentanyl
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Diagnostic
Official Title: Herb-Opioid Interactions

Resource links provided by NLM:


Further study details as provided by National Center for Complementary and Alternative Medicine (NCCAM):

Estimated Enrollment: 54
Study Start Date: September 2001
Estimated Study Completion Date: May 2005
Detailed Description:

Extract of St. John's wort (SJW: Hypericum perforatum) has gained widespread popularity as an over-the-counter, natural antidepressant. Until recently, SJW was thought to be well tolerated and relatively safe. Within the past year, adverse metabolic interactions have been reported between SJW and several narrow therapeutic index drugs, notably cyclosporine, indinavir and digoxin. The interactions are now recognized to involve induction of two drug disposition mechanisms: cytochrome P450 3A4 enzyme and the active efflux pump, P-glycoprotein, both leading to profound reductions in blood or plasma drug concentration that compromises the therapeutic efficacy of the affected drug. Natural and synthetic opioids are the first-line agents for the palliative treatment of severe pain that results from cancer and cancer treatment. It is well recognized that depression is a co-morbid condition of severe and poorly controlled cancer-related pain. Given the widespread recognition of St. Johns wort as a mood enhancer and natural antidepressant, cancer pain patients receiving opioid analgesics may well turn to this herbal preparation for relief of depressive symptoms.

The overall objective of this research proposal is to investigate if significant interactions occur between two widely used opioid analgesics -- oxycodone and fentanyl and St. John wort extract through laboratory-based studies in healthy volunteers. The studies will assess the potential clinical significance of the interactions with respect to opioid analgesia efficacy and side effects, and provide scientific insights into the pharmacokinetic mechanisms underlying any observed interactions.

The oxycodone arm of the study is designed to 1) investigate the induction of CYP3A4-mediated N-demethylation which is the major detoxification pathway for oxycodone, and 2) resolve the inductive effects of SJW on intestinal and hepatic CYP3A4 through intravenous and oral administrations of a CYP3A-specific, in vivo catalytic probe -midazolam.

The fentanyl arm of the study is designed to 1) assess the effects of SJW on the brain uptake and efflux kinetics of fentanyl through pharmacokinetic-pharmacodynamic (PK-PD) modeling of miotic response over time during and following intravenous infusion of the opioid, and 2) To evaluate the changes in analgesia and side effects of fentanyl upon pretreatment with SJW that may have resulted from induction of Pgp at the BBB.

Overall, the proposed research will provide a definitive assessment of the potential and clinical significance of adverse interactions between SJW and opioids in the context of cancer pain therapy.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Healthy male and female volunteers of all ethnic origins, within 25% of ideal body weight, between ages of 21 and 45 who are literate and proficient in the English language.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027014

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Investigators
Principal Investigator: Danny D. Shen, Ph.D. Fred Hutchinson Cancer Research Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00027014     History of Changes
Other Study ID Numbers: R01 AT000864-01
Study First Received: November 15, 2001
Last Updated: February 7, 2007
Health Authority: United States: Federal Government

Keywords provided by National Center for Complementary and Alternative Medicine (NCCAM):
opioid
St. John's wort
analgesia
metabolism
transporter

Additional relevant MeSH terms:
Fentanyl
Oxycodone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on August 21, 2014