Cannabidiol and Management of Endometriosis Pain

NCT ID: NCT04527003

Last Updated: 2025-04-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-04

Study Completion Date

2024-06-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The investigators are looking to conduct a study looking at the effects of cannabidiol (CBD) in patients with endometriosis. It is believed that CBD will improve both pain and quality of life. The study will last a total of 12 weeks and involve several onsite visits in addition to daily pain assessments.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The proposal is to conduct a randomized double-blind placebo-controlled pilot study to evaluate the effectiveness of cannabidiol on the management of endometriosis-related pain.

Subjects will be pre-screened from new and existing patients as well as from referral sites for the diagnosis of endometriosis. Potential subjects will be pre-screened for moderate to severe endometriosis associated pain (VAS \> 3) greater than 6 months. Those meeting all inclusion and exclusion criteria that who are willing to participate will receive a detailed history and physical exam, appropriate bloodwork and undergo informed consented at the Screening Visit. Baseline survey data will be collected. During Screening, the patient's will be asked to complete their daily electronic diaries and screened for daily reporting adherence.

Randomized subjects will receive either (1) placebo (2) low dose CBD (3) high dose CBD. This study will include an 8-week intervention period during which subjects will be asked to record daily electronic VAS scores, pain medication use and a number of other parameters. Subjects will return at week 12 for a 4 week post-treatment visit, where they can also chose to enroll in an optional pharmacokinetic study. Participants will complete the Endometriosis Health Profile-30 (EHP-30), Patient Global Assessments (PGAs), the Patient Global Impression of Change (PGIC) surveys and, if partnered and sexually active, the Female Sexual Function Index at various time points. Patients will also have bloodwork done to assess for circulating markers of inflammation, circulating CBD concentration levels and liver dysfunction throughout the study duration. Subjects will be screened for side effects and asked to record pain medication use throughout the duration of the study. Study drug compliance will be assessed.

At the completion of the study, all subjects will be offered the opportunity to do pharmacokinetic testing with sublingual CBD until a maximum number of 4 patients are enrolled. The testing will include 24 hours of monitoring with sequential blood draws to determine the pharmacokinetic parameters of sublingual CBD after administration and one salivary pH. They will be discharged at 24 hours and asked to return to the clinic at 48 hours for one final lab draw.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Endometriosis CBD Pelvic Pain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Double-blind of study team (PI, Sub-I's and all research staff) and subjects. Randomization will be completed by Investigational Pharmacy and will keep the blind.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group A - Placebo

Norethindrone acetate (5mg daily) + Placebo

Group Type PLACEBO_COMPARATOR

Norethindrone Acetate

Intervention Type DRUG

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Placebo

Intervention Type OTHER

a substance or treatment which is designed to have no therapeutic value

Group B - Low Dose CBD

Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)

Group Type ACTIVE_COMPARATOR

Cannabidiol (CBD) Extract

Intervention Type DRUG

Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system.

Norethindrone Acetate

Intervention Type DRUG

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Group C - High Dose CBD

Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)

Group Type ACTIVE_COMPARATOR

Cannabidiol (CBD) Extract

Intervention Type DRUG

Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system.

Norethindrone Acetate

Intervention Type DRUG

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cannabidiol (CBD) Extract

Cannabis is a well-known plant that contains more than 500 identified phytochemicals of which over 100 are cannabinoids. The most widely studied is 9-tetrahydrocannabinol (9-THC), which is the major psychoactive component of Cannabis, but Cannabidiol (CBD) has been increasingly favored for its reduced side effect profile and potential health benefits. CBD was first isolated from Cannabis in the 1940s. CBD, unlike 9-THC, does not bind to CB1 and CB2 receptors, which accounts for its lack of typical psychotropic effects, but is still appears to work via alternative mechanisms via the endocannabinoid system.

Intervention Type DRUG

Norethindrone Acetate

Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.

Intervention Type DRUG

Placebo

a substance or treatment which is designed to have no therapeutic value

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Females ages 18-45 years at the time of enrollment
2. A surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis with associated moderate to severe endometriosis related pain ( \> 3 on a VAS)
3. Is not expected to undergo gynecological surgery or other surgical procedure for treatment of endometriosis during the study period
4. Agrees to use approved contraception during the entire study if not surgically sterile
5. Patients using oral contraceptives, vaginal ring, injectable progesterone and/or GnRH agonists/antagonist for contraception and/or management of endometriosis, can be included if both they and their primary provider agree to stopping their medication and transitioning to Norethindrone acetate (NETA) as the primary treatment of endometriosis throughout the study period.
6. Patients using Long-acting reversible contraceptives (LARCs) for contraception and/or management of endometriosis can be included if both they and their primary provider agree to initiate Norethindrone (NETA) as the primary treatment of endometriosis throughout the study period

Exclusion Criteria

1. Women that are pregnant, breastfeeding or trying to conceive
2. Women with chronic daily opioid use and any chronic pain or frequently reoccurring pain condition, other than endometriosis, that is treated with opioids for \> 14 days per month.
3. Women that are currently using Cannabis based products or have used them within 30 days of enrollment
4. Non-English speaking or inability to read and understand English
5. Women with a BMI \> 35 kg/m2
6. Women with known liver disease, such as hepatitis, or with screening LFTS (AST/ALT) \> 3 times above the upper limits of normal (ULN) in the past year
7. Women with chronic alcohol use (defined as \> 3 drinks per day, averaged over one week)
8. Women with chronic use of drugs (defined as \> 10 days/month) that cause somnolence/sedation such as benzodiazepines or Central Nervous System (CNS) depressants that are unwilling or unable to discontinue the medications for the washout period and the duration of the study
9. Women who are currently taking Clobazam or Valproate and are unwilling/unable to discontinue the medication for the washout period and the duration of the study
10. Women with suicidal ideation or uncontrolled depression within the past year
11. Known history of or suspected breast cancer on screening physical exam
12. History of or active deep venous thrombosis or pulmonary embolism
13. History of or active arterial thromboembolic event (e.g. stroke, myocardial infarction)
14. Multiple (\> 3) risk factors for arterial vascular disease (e.g. uncontrolled hypertension, diabetes mellitus, hypercholesterolemia, obesity and smoking)
15. Current use of a progestin-containing contraceptive implant
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Milton S. Hershey Medical Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Kristin Riley, MD

Assistant Professor of Obstetrics and Gynecology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):511-9. doi: 10.1016/j.fertnstert.2012.06.029. Epub 2012 Jul 20.

Reference Type BACKGROUND
PMID: 22819144 (View on PubMed)

Giudice LC, Kao LC. Endometriosis. Lancet. 2004 Nov 13-19;364(9447):1789-99. doi: 10.1016/S0140-6736(04)17403-5.

Reference Type BACKGROUND
PMID: 15541453 (View on PubMed)

Behera M, Vilos GA, Hollett-Caines J, Abu-Rafea B, Ahmad R. Laparoscopic findings, histopathologic evaluation, and clinical outcomes in women with chronic pelvic pain after hysterectomy and bilateral salpingo-oophorectomy. J Minim Invasive Gynecol. 2006 Sep-Oct;13(5):431-5. doi: 10.1016/j.jmig.2006.05.007.

Reference Type BACKGROUND
PMID: 16962527 (View on PubMed)

Rafique S, Decherney AH. Medical Management of Endometriosis. Clin Obstet Gynecol. 2017 Sep;60(3):485-496. doi: 10.1097/GRF.0000000000000292.

Reference Type BACKGROUND
PMID: 28590310 (View on PubMed)

Lamvu G, Soliman AM, Manthena SR, Gordon K, Knight J, Taylor HS. Patterns of Prescription Opioid Use in Women With Endometriosis: Evaluating Prolonged Use, Daily Dose, and Concomitant Use With Benzodiazepines. Obstet Gynecol. 2019 Jun;133(6):1120-1130. doi: 10.1097/AOG.0000000000003267.

Reference Type BACKGROUND
PMID: 31135725 (View on PubMed)

Fasinu PS, Phillips S, ElSohly MA, Walker LA. Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents. Pharmacotherapy. 2016 Jul;36(7):781-96. doi: 10.1002/phar.1780.

Reference Type BACKGROUND
PMID: 27285147 (View on PubMed)

Hermanson DJ, Marnett LJ. Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev. 2011 Dec;30(3-4):599-612. doi: 10.1007/s10555-011-9318-8.

Reference Type BACKGROUND
PMID: 22038019 (View on PubMed)

Bouaziz J, Bar On A, Seidman DS, Soriano D. The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. Cannabis Cannabinoid Res. 2017 Apr 1;2(1):72-80. doi: 10.1089/can.2016.0035. eCollection 2017.

Reference Type BACKGROUND
PMID: 28861506 (View on PubMed)

Brawn J, Morotti M, Zondervan KT, Becker CM, Vincent K. Central changes associated with chronic pelvic pain and endometriosis. Hum Reprod Update. 2014 Sep-Oct;20(5):737-47. doi: 10.1093/humupd/dmu025. Epub 2014 Jun 11.

Reference Type BACKGROUND
PMID: 24920437 (View on PubMed)

Rocha MG, e Silva JC, Ribeiro da Silva A, Candido Dos Reis FJ, Nogueira AA, Poli-Neto OB. TRPV1 expression on peritoneal endometriosis foci is associated with chronic pelvic pain. Reprod Sci. 2011 Jun;18(6):511-5. doi: 10.1177/1933719110391279. Epub 2010 Dec 15.

Reference Type BACKGROUND
PMID: 21160085 (View on PubMed)

Bohonyi N, Pohoczky K, Szalontai B, Perkecz A, Kovacs K, Kajtar B, Orban L, Varga T, Szegedi S, Bodis J, Helyes Z, Koppan M. Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis. Mol Pain. 2017 Jan-Dec;13:1744806917705564. doi: 10.1177/1744806917705564.

Reference Type BACKGROUND
PMID: 28478727 (View on PubMed)

Sanchez AM, Vigano P, Mugione A, Panina-Bordignon P, Candiani M. The molecular connections between the cannabinoid system and endometriosis. Mol Hum Reprod. 2012 Dec;18(12):563-71. doi: 10.1093/molehr/gas037. Epub 2012 Aug 24.

Reference Type BACKGROUND
PMID: 22923487 (View on PubMed)

Devinsky O, Verducci C, Thiele EA, Laux LC, Patel AD, Filloux F, Szaflarski JP, Wilfong A, Clark GD, Park YD, Seltzer LE, Bebin EM, Flamini R, Wechsler RT, Friedman D. Open-label use of highly purified CBD (Epidiolex(R)) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav. 2018 Sep;86:131-137. doi: 10.1016/j.yebeh.2018.05.013. Epub 2018 Jul 11.

Reference Type BACKGROUND
PMID: 30006259 (View on PubMed)

Ewing LE, Skinner CM, Quick CM, Kennon-McGill S, McGill MR, Walker LA, ElSohly MA, Gurley BJ, Koturbash I. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules. 2019 Apr 30;24(9):1694. doi: 10.3390/molecules24091694.

Reference Type BACKGROUND
PMID: 31052254 (View on PubMed)

Millar SA, Stone NL, Yates AS, O'Sullivan SE. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front Pharmacol. 2018 Nov 26;9:1365. doi: 10.3389/fphar.2018.01365. eCollection 2018.

Reference Type BACKGROUND
PMID: 30534073 (View on PubMed)

Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018 Nov;84(11):2477-2482. doi: 10.1111/bcp.13710. Epub 2018 Aug 7.

Reference Type BACKGROUND
PMID: 30001569 (View on PubMed)

Roslawski MJ, Remmel RP, Karanam A, Leppik IE, Marino SE, Birnbaum AK. Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients. Ther Drug Monit. 2019 Jun;41(3):357-370. doi: 10.1097/FTD.0000000000000583.

Reference Type BACKGROUND
PMID: 30520828 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.fda.gov

HIGHLIGHTS OF PRESCRIBING INFORMATION. EPIDIOLEX ® (cannabidi ol) oral solution, CX \[pending DEA scheduling action\] Initial U.S. Approval: XXXX \[pending controlled substance scheduling\]

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

STUDY00013752

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Endometriosis Pain
NCT06101303 RECRUITING
Ketamine in Central Sensitization
NCT07182032 NOT_YET_RECRUITING PHASE4