Endometriosis, Pelvic Pain
Conditions
Keywords
Cannabis, Endometriosis, Pelvic Pain
Brief summary
The objective of this work is to conduct a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of cannabis extract in women with endometriosis who have already undergone hormonal contraceptive treatment and surgery without satisfactory response.
Detailed description
The Dreamland study is a two-arm, parallel-group, individually randomized (1:1 allocation ratio), controlled by disease stage, participant and investigator blinded, single-site superiority trial of oral cannabis extract (CBD). CBD will be given orally starting at 10 mg daily and up-titrated to a maximum dose of 150 mg daily. Dose up-titration will be based on clinical response or side effects, whichever comes first. After 63 days of treatment, gradual withdrawal will be performed during one week. Then, at 70 days, there will be an open-label extension wherein all participants from control group will be offered a course of CBD according to the same previous protocol. This research intends to : 1. Assess whether the daily use of CBD, for nine weeks, will reduce the pain level of these women. 2. Assess whether the daily use of CBD, for nine weeks, will modify pain threshold. 3. Assess whether the daily use of CBD, for nine weeks, will interfere in psychological symptoms. 4. Assess the possible adverse effects of using CBD
Interventions
DRUGCannabis Derivatives
CBD 10 mg (up-titrated until 150mg or adverse effects) daily for 9 weeks
DRUGPlacebo
Placebo 10 mg (up-titrated until 150mg or adverse effects) daily for 9 weeks
DRUGHormonal Contraceptive Agents
All participants will be given hormonal contraceptive.
Sponsors
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Volunteers, administrative staff, laboratory technicians, doctors who will carry out the assessments, and statisticians will be blind to the treatment group and will not know about the group treatment information.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with chronic pelvic pain secondary to endometriosis surgically treated, with refractory symptoms, and who are taking complementary hormone therapy; * Women over 18 years of age who wish to participate in the clinical trial; * Willingness to voluntarily participate in the study to accept randomization to either of the two treatment arms; * Participating exclusively in this clinical trial during the study period; * Possess a telephone (cell or landline) that may be available to receive daily calls throughout the study period; * Signature of the Free and Informed Consent Term (TCLE) approved by the Local Research Ethics Committee.
Exclusion criteria
* Chronic, severe or uncompensated medical conditions, such as: insulin-dependent diabetes (types 1 or 2); uncontrolled high blood pressure, lung disease such as asthma or other chronic obstructive pulmonary disease; hematological diseases, liver diseases, chronic kidney disease in advanced stage (grade 3, 4 and 5), metabolic disturbances and immunosuppression; * Use of any medication with potential interaction with CBD/THC (such as chloroquine, clobazan, warfarin, or valproic acid) or history of undesirable reactions prior to the use of this medications; * Inability to use oral medication; * Pregnancy or lactation; * History of alcohol or drug addiction; * Smoking in the last three years; * Marijuana use in the past three months or a lifetime history of dependence; * Inability to cooperate with investigators due to cognitive impairment or mental status.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with pain change of 30% | Time points for assess: Week 1, Week 3, Week 4, Week 5, Week 7, Week 8, Week 9; Data will be reported through study completion, an average of 1 year | Proportion of women with at least 30% of change in pain intensity. Pain intensity measured through visual analogue scale. |
| Proportion of patients with pain change of 50% | Time points for assess: Week 1, Week 3, Week 4, Week 5, Week 7, Week 8, Week 9; Data will be reported through study completion, an average of 1 year | Proportion of women with at least 50% of change in pain intensity. Pain intensity measured through visual analogue scale. |
| Quantitative change in pain intensity | Time points for assess: Week 1, Week 3, Week 4, Week 5, Week 7, Week 8, Week 9; Data will be reported through study completion, an average of 1 year | Absolute variation of pain intensity measured through visual analogue scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central sensitization change | Day 0, Day 63 | Changes in the score from Central Sensitization Inventory between the beginning (day 0) and the end of the protocol (day 63). Total scores ranging from 0-100. Higher scores mean a worse outcome. Score higher than 40 suggest central sensitization. |
| Brief measure for assessing generalized anxiety disorder | Day 0, Day 63 | Changes in the score from Generalized Anxiety Disorder (GAD7) scale between the beginning (day 0) and the end of the protocol (day 63). Total scores ranging from 0-21. Higher scores mean a worse outcome. Scores higher than 10 suggest generalized anxiety disorder. |
| Measure of the degree of depression severity | Day 0, Day 63 | Changes of scores for depressive symptoms over time during the study period (day 0-63) using Patient ́s Health Questionnaire-9 (PHQ-9). Total scores ranging from 0-27. Higher scores mean a worse outcome. Scores less than or equal to 4 suggest minimal depression. |
| Glucose | Week 0, Week 1, Week 5, Week 9. | Change in glucose concentration (glycemia) in plasma |
| Alanine aminotransferase (ALT) | Week 0, Week 1, Week 5, Week 9. | Change in ALT concentration in plasma |
| Cannabidiol (CBD) | Week 0, Week 1, Week 5, Week 9. | Change in CBD concentration in plasma |
| Tetrahydrocannabinol (THC) | Week 0, Week 1, Week 5, Week 9. | Change in THC concentration in plasma |
| Side effects | Week 0, Week 1 (Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7), Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9. Participants will be able to establish contact with a team doctor especially to report side effects. | Occurrence of side effects over time during the study period (day 0-63) |
| Bilirubin | Week 0, Week 1, Week 5, Week 9. | Change in bilirubin concentration in plasma |
| Aspartate aminotransferase (AST) | Week 0, Week 1, Week 5, Week 9. | Change in AST concentration in plasma |
| Pain threshold change | Day 0, Day 63 | Changes in the thermal peripheral pain thresholds: the range of temperatures at which a participant begins to perceive heat as painful: comparison between the beginning (day 0) and the end of the protocol (day 63). |
Countries
Brazil
Outcome results
None listed