Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001560785
Ethics application status
Approved
Date submitted
9/11/2022
Date registered
19/12/2022
Date last updated
19/10/2023
Date data sharing statement initially provided
19/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
EndoCannED – The effect of Medicinal Cannabis on emergency department presentations in people with endometriosis: a randomised, controlled feasibility study
Scientific title
EndoCannED – The effect of Medicinal Cannabis on emergency department presentations in people with endometriosis: a randomised, controlled feasibility study
Secondary ID [1] 308373 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
endometriosis 328169 0
Condition category
Condition code
Reproductive Health and Childbirth 325220 325220 0 0
Menstruation and menopause
Alternative and Complementary Medicine 325221 325221 0 0
Other alternative and complementary medicine
Reproductive Health and Childbirth 325546 325546 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Cannabidiol (CBD) Oil alone

Starting with 0.5ml of CBD oil (CBD isolate 100mg/mL) per day split into two doses 10-12 hours apart and ingested orally (0.25ml breakfast and 0.25ml dinner), providing a total dosage of 50mg of CBD per day. This will be increased by 0.2ml per day every two to three days (based on patient preference) until participants report either (a) a 20% or greater reduction in their daily pelvic pain severity as measured on a 0-10 numeric rating scale (NRS), or (b) they reach the maximum dosage of 300mg of CBD per day

Arm 2: CBD Oil + vapourised Tetrahydrocannabinol (THC) containing cannabis flower as required. Starting dosage and dosage finding as per Arm 1.

In addition, all participants will be provided with a TGA-approved vaporiser and 10g of a moderate THC cannabis flower (14% THC, <1% CBD) per month. Participants will be advised that if their pelvic pain is > 6/10 they may take up to two inhalations per session (equivalent ~5-7mg THC per inhalation) using the Foltin Uniform Puff Procedure where the user inhales for 5s and is then followed by a 10 s breath hold, then exhalation. They then wait for 10 minutes and decide if they need the second inhalation to reduce their pain to a manageble level. This process can be repeated up to 3 times per day, with at least 120 minutes between sessions.

Both Arm 1 and 2 will have a total duration of 3 months of intervention.

Compliance will be measured by returning of products at trial conclusion and then (a) measurement of remaining CBD oil in ml and (b) weighing of returned cannabis flower.
Intervention code [1] 324825 0
Treatment: Drugs
Comparator / control treatment
Arm 3: Placebo oil: A colour-matched oil identical to the CBD isolate - colour and flavour matched to CBD100mg/mL intervention. Composition is medium chain triglyceride oil with <0.5% beta-carotene. Beta-carotene is compliant with TGA regulatory document “Colourings used in medicines for topical and oral use” (CAS 160a(i)). No other excipients are utilised.
Control group
Placebo

Outcomes
Primary outcome [1] 333062 0
Acceptability and feasibility outcome #1: Recruitment rate (interest to participate in the trial, identification of appropriate recruitment strategies and the appropriateness of eligibility criteria)

Recruitment rate will be calculated as the number of people who are eligible for randomisation out of those who express interest in the trial via an audit of the study database.
Timepoint [1] 333062 0
end of followup (6 months after trial entry)
Primary outcome [2] 333063 0
Acceptability and feasibility outcome #2: Retention (compliance with treatment attendance and dropout rates)

Retention will be calculated as the number of people who complete all of the secondary outcome measures via an audit of the study database.
Timepoint [2] 333063 0
end of followup (6 months after trial entry)
Primary outcome [3] 333064 0
Feasibility outcome #3: Safety and adverse events.

1. Blood tests for liver and kidney function. These tests will consist of the following markers in the blood: liver enzymes, bilirubin and albumin (Liver Function Tests) and Urea and Electrolytes (U&E).
2. Adverse events will be assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE5.0). Potentially expected adverse events including dry mouth, somnolence, orthorexia will be assessed using a study specific self-report questionaaire that captures severity (mild, moderate, severe), impact on functioning (mild,moderate,severe), and duration (short <1 hr), moderate (1-6 hours), longer (>6 hours). All reported adverse events will be followed up by a member of the research team within 48 working hours of being reported.
Timepoint [3] 333064 0
Blood tests: Screening (prior to randomisation), end of first month of intervention (Month 1 after trial entry), End of intevention (3 months after trial entry), end of follow up (6 months after trial entry)

Adverse events: collected as part of weekly online surveys starting at the time of trial entry to 3 months after trial entry (end of intervention).
Secondary outcome [1] 415696 0
The number of emergency department presentations for pelvic pain. We will also collect information on the duration of stay and interventions needed during the visit. Participants will self report this during the study period. At the conclusion of the follow-up phase participants will be asked to provide a letter from their GP outlining the number, and duration of each stay as well as any reported interventions that occured in the ED.
Timepoint [1] 415696 0
Baseline (determined as the median number of visits per month in the 12 months prior to study onset), and at the end of each month during the intervention phase (3 months after trial entry) and each month during the follow-up phase (6 months after trial entry).
Secondary outcome [2] 415697 0
Overall pelvic pain severity as measured on a 0-10 numeric rating scale (NRS). A single 0-10 score will be provided for the average pelvic pain experienced in the past week.
Timepoint [2] 415697 0
Baseline, weekly from start of intervention till end of trial (3 months after trial entry), then once per month for the next 3 months until end of follow up (6 months after trial entry)
Secondary outcome [3] 415698 0
Most bothersome symptom. A participant nominated symptom (e.g. bloating) that they rank as their most bothersome or causes the most significant impact. Participants will be able to choose a catagory of symptom (e.g gastrointestinal, and then enter the symptom in their own words). Severity of this most bothersome symptom will be measured on a 0-10 NRS.
Timepoint [3] 415698 0
Baseline, weekly from start of intervention till end of trial (3 months after trial entry), then once per month for the next 3 months until end of follow up (6 months after trial entry)
Secondary outcome [4] 415699 0
The Endometriosis Health Profile 30 (EHP-30). The EHP-30 is a user friendly, valid and reliable condition-specific tool to assess health related quality of life (HRQoL) and contains questions on physical and emotional functioning as recommended by the IMMPACT guidelines. The recall period is the previous 4 weeks.
Timepoint [4] 415699 0
Baseline, the end of trial (3 months after trial entry), and end of the follow up-phase (6 months after trial entry)
Secondary outcome [5] 415700 0
The Pelvic Pain Impact Questionnaire (PPIQ) is a validated eight item tool used to capture the impact of pelvic pain on daily activities including energy levels, sitting, wearing certain clothing and exercising. The recall period is the previous 4 weeks.
Timepoint [5] 415700 0
Baseline, the end of trial (3 months after trial entry), and end of the follow up-phase (6 months after trial entry)
Secondary outcome [6] 415701 0
Changes in analgesic medication usage. This will capture usage of opioid and non-opioid medications (such as NSAIDs) used to manage pelvic pain. Brand/type of medication (e.g ibuprofen), dosage, and number of times used during the recall period will be captured.

Analgesic medication usage will be measured once per week, with a one week recall period using a questionaaire designed specifically for this study.
Timepoint [6] 415701 0
Baseline, weekly from start of intervention till end of trial (3 months after trial entry), then once per month for the next 3 months until end of follow up (6 months after trial entry)
Secondary outcome [7] 415702 0
Fatigue Severity Scale (FSS). The FSS is a nine item, seven-point questionnaire used to determine the impact of fatigue when performing daily activities. This tool uses a seven-day recall.
Timepoint [7] 415702 0
Baseline, the end of trial (3 months after trial entry), and end of the follow up-phase (6 months after trial entry)

Eligibility
Key inclusion criteria
Aged 20 years and over; able to read and write English fluently, be residing in the state of Victoria for the duration of the trial period, Diagnosis of endometriosis via laparoscopy, MRI or Ultrasound imaging by a medical doctor with input from an imaging specialist with specific endometriosis expertise; Have not used illicit cannabis or prescribed cannabinoid-based medications in the previous three months; Report no current, or history of, hazardous cannabis use or dependency; Agree to keep all study product stored in a secure location and not to share/distribute cannabis to any other individual; has access to a smartphone (either iOS or Android). If sexually active and pregnancy is a possibility, agree to use appropriate contraception to prevent pregnancy during the study period, agree not to consume alcohol during the titration and active phase of the trial, agree not to participate in any other clinical trial during the titration and active phase of the trial.
Minimum age
20 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Endometriosis-related surgery in the previous six months; Must not have started, stopped or had a significant change in dosage of any endometriosis specific medication in the last three months including contraceptives, GNRH-a, and neuroleptics (changes in ‘as needed’ medications such as analgesics are not reasons for exclusion); Upon review of medical or psychiatric history, must not have any current or past diagnosis that would be considered a risk to participation in the study, such as schizophrenia, psychosis, bipolar disorder, panic disorder, major depressive disorder, dissociative disorder, cannabis use disorder or obsessive-compulsive disorder; Currently have any major haematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, gastrointestinal (particularly hepatic), renal or neurological disease (determined by the medical monitoring team). Currently taking Immune modulators (e.g., cyclosporine), Mood-altering drugs (e.g., lithium carbonate) – not including antidepressants aside from tricyclics (mentioned below), Blood thinners (e.g., warfarin), Monoamine oxidase inhibitors (e.g., selegiline, phenelzine), Anti-arrhythmics (e.g., quinidine, disopyramide), Hypoglycaemics (e.g., insulin), Antiepileptics/anticonvulsants (e.g., phenytoin, valproic acid), Anti-HIV drugs (e.g., saquinavir), Antineoplastics (e.g., methotrexate), Barbiturates, Theophylline (1,3-dimethylxanthine), Cardiac glycosides (e.g., digoxin), St John’s wort. Known allergy to any of the compounds in the investigational products (e.g CBD, THC). Participation in another clinical trial during the past 30 days.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation is performed by REDCap's randomisation function and allocation is concealed by this software so that none of the research team has access to this.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation in a 1:1 ratio is performed by REDCap's randomisation function.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2023
Actual
10/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
63
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312619 0
Government body
Name [1] 312619 0
Victorian Government Department of Jobs, Precincts and Regions (Victorian Medical Research Accelerator)
Country [1] 312619 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
1 Gheringhap st, GEELONG, VICTORIA, 3220
Country
Australia
Secondary sponsor category [1] 314230 0
University
Name [1] 314230 0
Western Sydney University
Address [1] 314230 0
NICM Health Research Institute
Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Australia
Country [1] 314230 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311937 0
DEAKIN UNIVERSITY HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 311937 0
1 Gheringhap st, GEELONG, VICTORIA, 3220
Ethics committee country [1] 311937 0
Australia
Date submitted for ethics approval [1] 311937 0
14/11/2022
Approval date [1] 311937 0
19/04/2023
Ethics approval number [1] 311937 0
2022-342

Summary
Brief summary
Endometriosis is an oestrogen-dependent, chronic inflammatory condition characterised by the presence of endometrial-like tissue outside of the uterus in the form of lesions, affecting around 1 in 9 women and those assigned female at birth in Australia (~830,000 people) and has no cure. My research has shown that patients often have to make impossible choices between being in pain, and the worry of dependence, addiction and impairment due to the current drug choices. Effective pain relief with a low to negligible risk of addiction is the holy grail for people with endometriosis. Various phytochemicals (mainly cannabinoids) from Cannabis spp have well described analgesic, anti-inflammatory, anxiolytic, anti-depressant and anti-emetic actions. Cannabis use in other chronic pain conditions has resulted in “substitution” of pharmaceuticals, commonly opioid analgesics, by cannabis. Our previous research has shown that women with endometriosis in Australia and New Zealand are using cannabis, mostly from illicit sources, to manage their pain and other symptoms. We hypothesise that usage of either CBD isolate alone or in combination with THC containing canabis flower will reduce pelvic pain severity, and presentations to the emergency department. The primary aim of this project is to determine the feasibility, safety and acceptability of two different medicinal cannabis interventions in people with endometriosis
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122902 0
Prof Antonina Mikocka-Walus
Address 122902 0
Deakin University, Burwood Campus
221 Burwood Highway, Burwood, Victoria 3125
Country 122902 0
Australia
Phone 122902 0
+61392468575
Fax 122902 0
Email 122902 0
antonina.mikockawalus@deakin.edu.au
Contact person for public queries
Name 122903 0
Prof Antonina Mikocka-Walus
Address 122903 0
Deakin University, Burwood Campus
221 Burwood Highway, Burwood, Victoria 3125
Country 122903 0
Australia
Phone 122903 0
+61392468575
Fax 122903 0
Email 122903 0
antonina.mikockawalus@deakin.edu.au
Contact person for scientific queries
Name 122904 0
Prof Antonina Mikocka-Walus
Address 122904 0
Deakin University, Burwood Campus
221 Burwood Highway, Burwood, Victoria 3125
Country 122904 0
Australia
Phone 122904 0
+61392468575
Fax 122904 0
Email 122904 0
antonina.mikockawalus@deakin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17578Study protocol    This will be provided once ethics approval has bee... [More Details]
17579Informed consent form    This will be provided once ethics approval has bee... [More Details]
17580Ethical approval    This will be provided once ethics approval has bee... [More Details]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System.2023https://dx.doi.org/10.3390/jcm12227071
N.B. These documents automatically identified may not have been verified by the study sponsor.