- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04527003
Cannabidiol and Management of Endometriosis Pain
A Randomized Controlled Pilot Study of the Use of Cannabidiol in the Management of Endometriosis Pain
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Barbara Scheetz
- Phone Number: 717-531-4483
- Email: bscheetz@pennstatehealth.psu.edu
Study Contact Backup
- Name: Kristin Riley, MD
- Phone Number: 7175316446
- Email: kriley1@pennstatehealth.psu.edu
Study Locations
-
-
Pennsylvania
-
Hershey, Pennsylvania, United States, 17033
- Recruiting
- Penn State Health Milton S. Hershey Medical Center
-
Contact:
- Heidi N Watts, BSN, RN
- Phone Number: 717-531-6272
- Email: hwatts@pennstatehealth.psu.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Females ages 18-45 years at the time of enrollment
- A surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis with associated moderate to severe endometriosis related pain ( > 3 on a VAS)
- Is not expected to undergo gynecological surgery or other surgical procedure for treatment of endometriosis during the study period
- Agrees to use approved contraception during the entire study if not surgically sterile
- 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.
- 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:
- Women that are pregnant, breastfeeding or trying to conceive
- 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.
- Women that are currently using Cannabis based products or have used them within 30 days of enrollment
- Non-English speaking or inability to read and understand English
- Women with a BMI > 35 kg/m2
- 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
- Women with chronic alcohol use (defined as > 3 drinks per day, averaged over one week)
- 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
- 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
- Women with suicidal ideation or uncontrolled depression within the past year
- Known history of or suspected breast cancer on screening physical exam
- History of or active deep venous thrombosis or pulmonary embolism
- History of or active arterial thromboembolic event (e.g. stroke, myocardial infarction)
- Multiple (> 3) risk factors for arterial vascular disease (e.g. uncontrolled hypertension, diabetes mellitus, hypercholesterolemia, obesity and smoking)
- Current use of a progestin-containing contraceptive implant
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Group A - Placebo
Norethindrone acetate (5mg daily) + Placebo
|
Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.
a substance or treatment which is designed to have no therapeutic value
|
Active Comparator: Group B - Low Dose CBD
Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)
|
Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.
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.
|
Active Comparator: Group C - High Dose CBD
Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)
|
Norethindrone is a form of progesterone, a female hormone important for regulating ovulation and menstruation.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pain Score
Time Frame: 8 weeks
|
Pain will be reported daily using the Visual Analog Scale, a 100mm horizontal line on which the patient's pain intensity is represented by a point between the extremities of 0 (no pain) and 100 (worst pain).
The primary study endpoint will be compared between groups using the area under the curve.
|
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Total FSFI Score
Time Frame: Baseline and 12 weeks
|
The Female Sexual Function Index (FSFI) is a validated survey.
The total FSFI score ranges from 2 (low sexual function) to 36 (high sexual function).
|
Baseline and 12 weeks
|
Change in EHP-30 Core Domain
Time Frame: Baseline and 12 weeks
|
The Endometriosis Health Profile-30 (EHP-30) is a validated questionnaire measuring quality of life in women with endometriosis.
A summary score is calculated for the core domain on a scale of 0 to 100 (0 indicates the best possible health status whereas 100 indicates the worst possible health status).
|
Baseline and 12 weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
- Giudice LC, Kao LC. Endometriosis. Lancet. 2004 Nov 13-19;364(9447):1789-99. doi: 10.1016/S0140-6736(04)17403-5.
- 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.
- Rafique S, Decherney AH. Medical Management of Endometriosis. Clin Obstet Gynecol. 2017 Sep;60(3):485-496. doi: 10.1097/GRF.0000000000000292.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pain
- Neurologic Manifestations
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Endometriosis
- Pelvic Pain
- Physiological Effects of Drugs
- Anticonvulsants
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptives, Oral
- Contraceptive Agents, Female
- Contraceptives, Oral, Synthetic
- Contraceptives, Oral, Hormonal
- Norethindrone
- Norethindrone Acetate
- Cannabidiol
Other Study ID Numbers
- STUDY00013752
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Endometriosis
-
Fabio BarraCompletedEndometriosis | Endometriosis, Rectum | Endometriosis of Vagina | Endometriosis Rectovaginal Septum | Endometriosis Pelvic | Endometriosis of ColonItaly
-
Ospedale Policlinico San MartinoCompletedEndometriosis | Bowel Endometriosis | Endometriosis, Rectum | Endometriosis ColonItaly
-
BioGene Pharmaceutical Ltd.WithdrawnSafety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis (ELTA)Endometriosis | Endometriosis Ovary | Endometriosis, Rectum | Endometriosis ExternaSwitzerland
-
Fondazione IRCCS Ca' Granda, Ospedale Maggiore...CompletedEndometriosis | Endometriosis-related Pain | Endometriosis Thoracic | Endometriosis of Lung | Endometriosis of PleuraItaly
-
Ospedale Policlinico San MartinoCompletedEndometriosis, Rectum | Endometriosis, SigmoidItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaUnknownBowel Endometriosis | Endometriosis, RectumItaly
-
Ospedale Policlinico San MartinoActive, not recruitingEndometriosis, Rectum | Endometriosis of ColonItaly
-
Catholic University of the Sacred HeartCompletedPelvic Endometriosis | Endometriosis Outside PelvisItaly
-
Semmelweis UniversityUniversity of PecsNot yet recruitingEndometriosis | Endometriosis Ovary | Endometriosis Rectovaginal Septum
-
Catholic University of the Sacred HeartCompletedPelvic Endometriosis | Endometriosis Outside PelvisItaly
Clinical Trials on Norethindrone Acetate
-
Milton S. Hershey Medical CenterCompleted
-
Boston Children's HospitalBrigham and Women's HospitalCompleted
-
Baylor Research InstituteMerck Sharp & Dohme LLCTerminatedContraception | Breakthrough Bleeding | Implant | Birth Control | Uterine BleedingUnited States
-
Scott and White Hospital & ClinicUnknownMenorrhagia | Heavy Menstrual Bleeding | HypermenorrheaUnited States
-
Norton HealthcareCompletedEtonogestrel Contraceptive Implant, Bothersome BleedingUnited States
-
Teva Pharmaceuticals USACompleted
-
Teva Pharmaceuticals USACompleted
-
Boston Children's HospitalNot yet recruiting
-
Warner ChilcottCompleted
-
Assiut UniversityNot yet recruiting