- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04374773
Effects of Pregnancy-associated Hormones on THC Metabolism in Women (PrECEPT)
November 29, 2023 updated by: Nina Isoherranen, University of Washington
Effect of Estradiol and Cortisol on Marinol Metabolism
Cannabis use is prevalent among pregnant women, but the effects of use on both the developing fetus and pregnant woman are unknown.
Importantly, drug exposure could be influenced by the impact of pregnancy-associated hormones on the metabolism of tetrahydrocannabinol (THC), the main psychoactive component of cannabis.
The goal of this study is to determine whether cortisol and estradiol - hormones that rise dramatically during pregnancy - increase the clearance of dronabinol (THC) in reproductive age women to simulate the pregnant state.
The collected data will then be used to predict the time course and magnitude of changes in THC metabolism in pregnant women, particularly with gradually increasing estradiol and cortisol concentrations that evolve over the course of pregnancy.
The overall objective of this study is to better understand the effects of THC use during pregnancy on the health of the pregnant woman and developing fetus.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Tetrahydrocannabinol (THC) is approved as a medicinal treatment under the trade name dronabinol but is also a drug of abuse when consumed as part of cannabis products.
With the legalization of recreational cannabis use and increased use among pregnant women, there is new urgency to understand the dose-exposure relationship for THC, the mechanisms by which THC is eliminated from the body, and the impact of the hormonal milieu of pregnancy on these mechanisms.
As approximately 4% of all pregnant women in the United States use cannabis, there is a critical need for studies evaluating how cannabis metabolism may change during pregnancy leading to altered exposures, pharmacology, and toxicology.
Recent studies suggest that cannabis exposure during pregnancy may adversely affect the developing fetus, and administration of cannabis [or dronabinol (THC)] to pregnant women is therefore not ethical.
Analysis of THC exposures and effects during pregnancy is significantly hindered by the lack of accurate, quantitative biomarkers of THC exposure and the unreliable self-report of cannabis use.
To address these gaps, the current study is designed to 1) characterize the dose-exposure relationship of THC and its major metabolites 11-OH-THC and 11-nor-carboxy-THC in reproductive age women following consumption of dronabinol orally and 2) to determine how THC metabolism is altered by the pregnancy-associated hormones estradiol and cortisol.
Existing data show that THC and its major metabolites are cleared by metabolizing enzymes whose activity increases during pregnancy and further has been shown to be induced specifically by estradiol and cortisol, hormones that are markedly increased during pregnancy.
Based on these data, we hypothesize that increasing estradiol and cortisol concentrations during pregnancy will increase the clearance of THC and its metabolites, leading to an altered metabolism in pregnant women when compared to non-pregnant individuals.
Our clinical study seeks to determine the magnitude of changes in THC pharmacokinetics in healthy female volunteers following exposures to increased estradiol and cortisol.
We predict that increased estradiol and cortisol concentrations will result in induction of THC-metabolizing enzymes in the liver and intestine, resulting in increased clearance of THC and its metabolites.
The clinical study will provide the foundation for modeling and simulation of THC disposition during human pregnancy.
These studies will also provide seminal data to allow modeling of the THC metabolome in human plasma and urine as a function of THC dose and time after consumption, making a significant impact on development of reliable biomarkers of THC exposures in humans.
Study Type
Interventional
Enrollment (Estimated)
12
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98125
- Nina Isoherranen
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years to 43 years (Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Healthy, premenopausal women ages 21-45 years old
- Body mass index (BMI) <30 kg/m2
- Regular menstrual periods (monthly, cycle 28-35 days in length)
- Willingness to use nonhormonal methods of contraception during the study period
Exclusion Criteria:
- History of diabetes or significant cardiac, kidney (eGFR<60 mL/min/1.73m2), gastrointestinal or liver disease
- History of blood clots or stroke
- Allergy to dronabinol, synthetic steroids, or any other chemically related drug or steroid
- Current or recent ingestion (<3 weeks) of any medication or herbal supplement known to be an inducer or inhibitor of CYP2C9, CYP3A4 or UGT. These include some anticoagulants, anti-psychotics, antibiotics, antifungal agents, antidepressants, anti-retroviral agents and herbal supplements (or other over-the-counter medications and supplements). Subjects who are taking any of these prescription drugs will not be asked to discontinue treatment but will be ineligible for study participation. Subjects taking excluded over-the-counter medications and/or supplements will be given the option of discontinuing these for 1 month prior to study participation.
- Current pregnancy or lactation
- History of use of illicit drugs or smoking within the last year
- Any recreational or medicinal use of cannabis or other forms of THC within 3 months
- Current use of amphetamines, anticholinergic drugs or antidepressants
- History of seizure disorder or psychiatric illness (mania or schizophrenia; major depression within the past year or >2 episodes lifetime)
- Current use of live or live attenuated vaccines
- Personal or family (1st degree relative) history of breast or ovarian cancer
- Systemic disease (cancer, auto-immune disease, chronic infection, etc)
- Current or recent (within 6 months) use of hormonal contraceptives
- History of severe hypertriglyceridemia (>300 mg/dL or history of acute pancreatitis)
- Uncontrolled hypertension (BP>140/90)
- Allergy to sesame oil
- Anemia (Hct <34 g/dL)
- Extensive skin disease (eczema, psoriasis, etc) that would preclude use of transdermal estradiol
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Estradiol
1 week treatment with 0.3 mg/24 hr transdermal estradiol
|
2.5 mg PO administered once prior to and once after 1 week of hormone therapy
Other Names:
|
Experimental: Cortisol
1 week treatment with 30 mg hydrocortisone daily, administered in 2 divided doses
|
2.5 mg PO administered once prior to and once after 1 week of hormone therapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dronabinol exposure
Time Frame: 24 hours
|
Area under plasma concentration-time curve (AUC) for THC
|
24 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
THC primary metabolite exposure
Time Frame: 24 hours
|
Area under plasma concentration-time curve (AUC) for 11-OH-THC
|
24 hours
|
THC secondary metabolite exposure
Time Frame: 24 hours
|
Area under plasma concentration-time curve (AUC) for 11-nor-COOH-THC
|
24 hours
|
Pharmacologic effects of THC
Time Frame: 12 hours
|
Visual analog scale ratings of subjective 'high'
|
12 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Nina Isoherranen, PhD, University of Washington
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 19, 2020
Primary Completion (Estimated)
December 31, 2023
Study Completion (Estimated)
May 31, 2024
Study Registration Dates
First Submitted
April 30, 2020
First Submitted That Met QC Criteria
April 30, 2020
First Posted (Actual)
May 5, 2020
Study Record Updates
Last Update Posted (Actual)
November 30, 2023
Last Update Submitted That Met QC Criteria
November 29, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Marijuana Abuse
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Psychotropic Drugs
- Hallucinogens
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Dronabinol
Other Study ID Numbers
- STUDY00008064
- 2P01DA032507-06A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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