Back to resultsCannabidiol for the Treatment of Pelvic Pain in Endometriosis (DREAMLAND) (DREAMLAND)
Primary Purpose
Endometriosis, Pelvic Pain
Status
Recruiting
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Cannabis Derivatives
Placebo
Hormonal Contraceptive Agents
Sponsored by
About this trial
This is an interventional treatment trial for Endometriosis focused on measuring Cannabis, Endometriosis, Pelvic Pain
Eligibility Criteria
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.
Sites / Locations
- Center of Chronic Pelvic Pain and Gynecologic Endoscopy of Ribeirao Preto Medical School, University of Sao PauloRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cannabis Derivatives
Placebo
Arm Description
Cannabis Derivatives (98% CBD, 2% THC) 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. All patients will take hormonal contraceptives, preferably progestagen-only. All participants will perform invasive and non-invasive procedures with the nursing team. The invasive will be blood collections, to evaluate laboratory parameters. The non-invasive ones refer to the measurement of height, weight, body temperature, and sleep pattern, as will pain threshold. In addition, they will be monitored through weekly self-assessment scales, applied remotely, electronically (cell phones or computers), with an estimated duration of ten minutes each, which will have their responses recorded in an electronic database, by the study coordination team.
Placebo will be given at the same protocol described before. The bottle, label, color and density of the contents will be the same. All patients will take hormonal contraceptives, preferably progestagen-only. Then, at 70 days, there will be an open-label extension wherein all participants from control group will be offered a course of active treatment according to the same previous protocol. All participants will perform invasive and non-invasive procedures with the nursing team. The invasive will be blood collections, to evaluate laboratory parameters. The non-invasive ones refer to the measurement of height, weight, body temperature, and sleep pattern, as will pain threshold. In addition, they will be monitored through weekly self-assessment scales, applied remotely, electronically (cell phones or computers), with an estimated duration of ten minutes each, which will have their responses recorded in an electronic database, by the study coordination team.
Outcomes
Primary Outcome Measures
Proportion of patients with pain change of 30%
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%
Proportion of women with at least 50% of change in pain intensity. Pain intensity measured through visual analogue scale.
Quantitative change in pain intensity
Absolute variation of pain intensity measured through visual analogue scale
Secondary Outcome Measures
Pain threshold change
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).
Central sensitization change
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
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
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.
Alanine aminotransferase (ALT)
Change in ALT concentration in plasma
Aspartate aminotransferase (AST)
Change in AST concentration in plasma
Glucose
Change in glucose concentration (glycemia) in plasma
Bilirubin
Change in bilirubin concentration in plasma
Cannabidiol (CBD)
Change in CBD concentration in plasma
Tetrahydrocannabinol (THC)
Change in THC concentration in plasma
Side effects
Occurrence of side effects over time during the study period (day 0-63)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05670353
Brief Title
Cannabidiol for the Treatment of Pelvic Pain in Endometriosis (DREAMLAND)
Acronym
DREAMLAND
Official Title
Cannabidiol in the Treatment of Women With Chronic Pelvic Pain Secondary to Endometriosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2023 (Actual)
Primary Completion Date
August 20, 2023 (Anticipated)
Study Completion Date
August 20, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 :
Assess whether the daily use of CBD, for nine weeks, will reduce the pain level of these women.
Assess whether the daily use of CBD, for nine weeks, will modify pain threshold.
Assess whether the daily use of CBD, for nine weeks, will interfere in psychological symptoms.
Assess the possible adverse effects of using CBD
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometriosis, Pelvic Pain
Keywords
Cannabis, Endometriosis, Pelvic Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
102 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cannabis Derivatives
Arm Type
Experimental
Arm Description
Cannabis Derivatives (98% CBD, 2% THC) 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.
All patients will take hormonal contraceptives, preferably progestagen-only.
All participants will perform invasive and non-invasive procedures with the nursing team. The invasive will be blood collections, to evaluate laboratory parameters. The non-invasive ones refer to the measurement of height, weight, body temperature, and sleep pattern, as will pain threshold. In addition, they will be monitored through weekly self-assessment scales, applied remotely, electronically (cell phones or computers), with an estimated duration of ten minutes each, which will have their responses recorded in an electronic database, by the study coordination team.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be given at the same protocol described before. The bottle, label, color and density of the contents will be the same.
All patients will take hormonal contraceptives, preferably progestagen-only. Then, at 70 days, there will be an open-label extension wherein all participants from control group will be offered a course of active treatment according to the same previous protocol.
All participants will perform invasive and non-invasive procedures with the nursing team. The invasive will be blood collections, to evaluate laboratory parameters. The non-invasive ones refer to the measurement of height, weight, body temperature, and sleep pattern, as will pain threshold. In addition, they will be monitored through weekly self-assessment scales, applied remotely, electronically (cell phones or computers), with an estimated duration of ten minutes each, which will have their responses recorded in an electronic database, by the study coordination team.
Intervention Type
Drug
Intervention Name(s)
Cannabis Derivatives
Intervention Description
CBD 10 mg (up-titrated until 150mg or adverse effects) daily for 9 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 10 mg (up-titrated until 150mg or adverse effects) daily for 9 weeks
Intervention Type
Drug
Intervention Name(s)
Hormonal Contraceptive Agents
Intervention Description
All participants will be given hormonal contraceptive.
Primary Outcome Measure Information:
Title
Proportion of patients with pain change of 30%
Description
Proportion of women with at least 30% of change in pain intensity. Pain intensity measured through visual analogue scale.
Time Frame
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
Title
Proportion of patients with pain change of 50%
Description
Proportion of women with at least 50% of change in pain intensity. Pain intensity measured through visual analogue scale.
Time Frame
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
Title
Quantitative change in pain intensity
Description
Absolute variation of pain intensity measured through visual analogue scale
Time Frame
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
Secondary Outcome Measure Information:
Title
Pain threshold change
Description
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).
Time Frame
Day 0, Day 63
Title
Central sensitization change
Description
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.
Time Frame
Day 0, Day 63
Title
Brief measure for assessing generalized anxiety disorder
Description
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.
Time Frame
Day 0, Day 63
Title
Measure of the degree of depression severity
Description
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.
Time Frame
Day 0, Day 63
Title
Alanine aminotransferase (ALT)
Description
Change in ALT concentration in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Aspartate aminotransferase (AST)
Description
Change in AST concentration in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Glucose
Description
Change in glucose concentration (glycemia) in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Bilirubin
Description
Change in bilirubin concentration in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Cannabidiol (CBD)
Description
Change in CBD concentration in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Tetrahydrocannabinol (THC)
Description
Change in THC concentration in plasma
Time Frame
Week 0, Week 1, Week 5, Week 9.
Title
Side effects
Description
Occurrence of side effects over time during the study period (day 0-63)
Time Frame
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.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Omero B Poli-Neto, MD; PhD
Phone
551636022583
Email
polineto@usp.br
First Name & Middle Initial & Last Name or Official Title & Degree
Rodrigo Ratochinski, MsC
Phone
5516997375882
Email
rratochinski@hcrp.usp.br
Facility Information:
Facility Name
Center of Chronic Pelvic Pain and Gynecologic Endoscopy of Ribeirao Preto Medical School, University of Sao Paulo
City
Ribeirão Preto
State/Province
Sao Paulo
ZIP/Postal Code
14049-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rodrigo Ratochinski, MsC
Phone
5516997375882
Email
rratochinski@hcrp.usp.br
First Name & Middle Initial & Last Name & Degree
Omero B Poli-Neto, MD, PhD
First Name & Middle Initial & Last Name & Degree
Julio C Rosa-e-Silva, MD,PhD
First Name & Middle Initial & Last Name & Degree
Jose A S Crippa, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jaime E C Hallak, MD, PhD
First Name & Middle Initial & Last Name & Degree
Wilson Marques Jr, MD, PhD
First Name & Middle Initial & Last Name & Degree
Antonio W Zuardi, MD, PhD
First Name & Middle Initial & Last Name & Degree
Antonio A Nogueira, MD, PhD
First Name & Middle Initial & Last Name & Degree
Francisco J Candido-dos-Reis, MD, PhD
First Name & Middle Initial & Last Name & Degree
Gabrielle B Anelli, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification
IPD Sharing Time Frame
Immediately the following publication. No end date
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal. Depending on the level of the proposed use of data, approval by an independent review committee will be required for the identified purpose.
Learn more about this trial
Cannabidiol for the Treatment of Pelvic Pain in Endometriosis (DREAMLAND)
We'll reach out to this number within 24 hrs