Efficacy of a topical cannabinoid preparation in decreasing symptoms of rheumatoid arthritis.

Plain English Summary

Background and study aims
In the past ten years, there have been major developments in the use of cannabis and its derivatives (called cannabinoids) for a variety of problems such as gastrointestinal function, nausea and vomiting, pain relief and depression. Studies show that cannabinoids can achieve the following: treatment of pain symptoms with fibromyalgia and neuropathic pain, reducing spasticity in multiple sclerosis, alleviating psychotic symptoms of schizophrenia and treatment of gastrointestinal inflammation due to Crohn's disease. In 2006, the first study using a cannabis-based medicine to treat pain caused by rheumatoid arthritis found significant improvements in pain but the effect size was small and variable across the sample population and further studies are required. As usual pain relief medications for all the conditions described above are often associated with potential harmful side effects, exploring less toxic pain killers is needed. This study will assess whether a topical cannabinoid preparation (cream) applied to the affected finger joints on the hands of individuals with rheumatoid arthritis can significantly reduce joint pain and whether this leads to increased physical mobility and improved quality of life.

Who can participate?
Individuals who have been diagnosed with rheumatoid arthritis who are between the ages of 21 and 75.

What does the study involve?
Participants will be given a numbered informed consent form to read and sign. Using the number on the consent form they will be allocated to one of two treatments (active dose or placebo dose) via a computer generated random number sequence. Expected duration of the participation after screening is 12 weeks. A number of measures will be taken and questionnaires will be filled at several milestones during the study. As it likely that some participants will be on standard medication for their active arthritis, their treatment regime will need to be stable for at least 30 days prior to actual participation in study. All participants will be asked to self-report their experience of finger joint pain at rest on a scale from 0 – 10, where the higher number indicates more pain, prior to the application of the topical cannabinoid preparation and, again, 10 minutes following each application. Participants in either the active dose and the placebo dose conditions will be asked to apply a topical cream preparation on two or three of the most affected finger joints on each hand three times daily. Participants will be instructed to measure 0.2ml of cream from the syringe onto the affected finger joint and massage in well, for approximately one minute, until the cream is completely absorbed into the skin. This will be repeated for each affected joint. Maximum total daily dose will be 5ml of cream. The participant should not use more than 100ml of cream for the two three-week phases of this study.

What are the possible benefits and risks of participating?
Participants will be providing information that will show the effects of a topical cannabinoid cream preparation for the treatment of pain experienced with rheumatoid arthritis. There may or may not be direct medical benefit to participants. Those in the active treatment dose may experience pain relief from joint pain. It is hoped that the information learned from the study will benefit other individuals with rheumatoid arthritis in the future.
A review of previous studies of cannabinoids for the treatment of chronic non-cancer pain indicated no serious adverse effects according to the Health Canada definition and the most common adverse events consisted of sedation, dizziness, dry mouth, nausea, and disturbances in concentration. The one possible anticipated risk to the use of the topical cannabinoid preparation is for the participant to develop a skin reaction or some swelling. If this does occur, participants will be advised to discontinue use of the topical preparation immediately and to inform the investigators. They will inform the participant’s primary doctor who, with the investigators, will then provide ongoing monitoring of the reaction until the adverse reaction has resolved or is stabilized.

Where is this study run from?
Medicinal Cannabis Resource Centre Inc (MCRCI) in Vancouver, BC, Canada. All data at the start of the study will obtained at MCRCI. Data obtained at midpoint, end and follow-up may be obtained from the participant's home or MCRCI, whichever is more convenient for the participant.

When is the study starting and how long is it expected to run for?
The study is ecpected to start in June 2014 and will run for 12 weeks or until the required number of 34 participants have completed the study.

Who is funding the study?
The principle investigator of the study, Dr. Cara Zaskow, is receiving funding through a paid educational leave at Capilano University, Psychology Department, to conduct this study. Other costs affiliated with the study are also being supported by the Medicinal Cannabis Resource Centre Inc (MCRCI), Canada.

Who is the main contact?
Dr. Cara Zaskow
czaskow@capilanou.ca

Trial website

Type

Scientific

Primary contact

Dr Cara Zaskow

ORCID ID

Contact details

Psychology Department
Capilano University
2055 Purcell Way
North Vancouver
BC
North Vancouver
V7J3H5
Canada
+1 604 9861911 local 2464
czaskow@capilanou.ca

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Scientific title

Efficacy of a topical cannabinoid preparation in decreasing symptoms of rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study

Acronym

Study hypothesis

The primary objective of this clinical pilot trial is to investigate whether a topical cannabinoid preparation applied to the affected finger joints on the hands of individuals with rheumatoid arthritis can provide a significant analgesic effect resulting in the reduction of joint pain at rest. Secondary objectives include a determination if a reduction of pain is followed by increased mobility in the hand an improved quality of life.

Ethics approval

Not provided at time of registration

Study design

Randomized double-blind placebo-controlled pilot study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a participant information sheet

Condition

Rheumatoid arthritis

Intervention

Participants in either the active dose (7.5 grams of finely ground plant material per 100 ml of transdermal cream = 0.94% cannabinoid) and the placebo dose conditions will be asked to apply the cream to two or three of the most affected finger joints on each hand three times daily. Participants will be instructed to measure 0.2ml of cream from the syringe onto the affected finger joint and massage in well, for approximately one minute, until the cream is completely absorbed into the skin. This dosing regimen will be repeated for each affected joint. Maximum total daily dose will be five milliliters (5ml) of cream. The participant should not use more than 100ml of cream for the two three-week phases of this clinical trial.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The primary endpoint assessed will be daily pain experience as self-reported by the participants measured by a 0 – 10 Numeric Rating Scale (NRS) 10 minutes following the application of the topical cream preparation (either active dose or placebo dose). The daily NRS rating will be then be averaged for measurements points obtained at midway through the 6 week clinical trial, at the end of the clinical trial and finally at 2 week follow-up.

Secondary outcome measures

Secondary endpoints will include:
1. Assessment of functional status using scores on the Stanford Health Assessment Questionnaire (HAQ, full version, Fries, Spitz, Kraines & Holman, 1980). This is a self-administered, 41 item measure that contains 8 categories which review a specific function evaluating difficulty with activities of daily living (e.g., dressing, grooming, arising, eating, walking, hygiene, errands and chores) over the past week. Also identified are specific aids or devices utilized for assistance such as help needed from another person.
2. Assessment of self-reported activities of daily living and quality of life as measured by the Rheumatoid Arthritis Quality of Life (RAQL, De Jong, van der Heijde, McKenna & Whalley, 1997). This is a self-administered 30 item measure that is answered on a yes/no basis.
3. In addition two measures of physical function developed by Escalante, Hass, and Del Rincon (2004) will be used to provide reproducible, quantitative and objective information about the individual’s current level of functional strength and dexterity. One, Grip Strength measured with a device such as a hand-held dynamometer (digital versions available). In a sitting position, with the elbow held at 90 degrees and the forearm supported on a flat horizontal surface, the person is asked to squeeze the handle with as much strength as possible. Three repetitions for each hand will be obtained and the mean value for all repetitions for each hand will be recorded. The second measure of physical function is the Timed Button Test in which the participant is asked to wear a standard 8 button men's or women's extra large shirt and fasten the front buttons. Stop watch timing is activated from the moment the person takes the shirt and is stopped when all the buttons have been fastened. Measurements for all the secondary endpoints are to be obtained at baseline, midway through the 6 week clinical trial, at the end of the clinical trial and finally at 2 week follow-up.

Overall trial start date

02/06/2014

Overall trial end date

01/12/2014

Reason abandoned

Participant inclusion criteria

Males and females between the ages of 21 – 75 with a diagnosis of rheumatoid arthritis of the proximal interphalangeal joints that is not adequately controlled by standard medication and remain symptomatic.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

34

Participant exclusion criteria

1. A history of psychiatric disorders or substance misuse
2. Severe cardiovascular
3. Renal of hepatic disorder
4. A history of epilepsy
5. Recreational or medicinal use of cannabis within the last 6 months

Recruitment start date

02/06/2014

Recruitment end date

01/12/2014

Countries of recruitment

Canada

Trial participating centre

Psychology Department
North Vancouver
V7J3H5
Canada

Organisation

Medicinal Cannabis Resource Centre Inc (Canada)

Sponsor details

c/o Terry Roycroft
President
450 Nanaimo Street
Vancouver
BC
Vancouver
V5L4W3
Canada
+1 604 566 9391
info@mcrci.com

Sponsor type

Research organisation

Website

Funder type

University/education

Funder name

Capilano University, Psychology Department (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medicinal Cannabis Resource Centre Inc. (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations