Cannabidiol and Management of Endometriosis Pain

Phase 3

Terminated

Conditions: Endometriosis
CBD
Pelvic Pain

Interventions: Drug: Norethindrone Acetate
Drug: Cannabidiol (CBD) Extract
Other: Placebo

Registration Number: NCT04527003

Lead Sponsor: Milton S. Hershey Medical Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 12

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A - Placebo	Placebo	Norethindrone acetate (5mg daily) + Placebo
Group A - Placebo	Norethindrone Acetate	Norethindrone acetate (5mg daily) + Placebo
Group C - High Dose CBD	Cannabidiol (CBD) Extract	Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)
Group C - High Dose CBD	Norethindrone Acetate	Norethindrone acetate (5mg daily) + High dose CBD (20mg sublingual daily)
Group B - Low Dose CBD	Norethindrone Acetate	Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)
Group B - Low Dose CBD	Cannabidiol (CBD) Extract	Norethindrone acetate (5mg daily) + Low dose CBD (10mg sublingual daily)

Primary Outcome Measures

Name	Time	Method
Pain Score Area Under the Curve (AUC)	8 weeks	Pain will be self-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). Although the daily collection is based on the 0-100 point scale, the primary study endpoint is calculated as the area under the curve per patient using the trapezoidal rule, with an AUC range per patient of 0-5600 over 8 weeks.

Secondary Outcome Measures