Osteo Arthritis KneeNCT04971629
The Relationship Between Cannabis Use, Biomarkers, Tissue Cannabinoid Levels and Clinical Outcomes in Patients With OA
An observational study of Osteo Arthritis Knee, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability, affecting the quality of life, pain, and physical functioning of 4.6 million Canadians. About half of OA patients have limited response to primary therapy. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Osteo Arthritis Knee
- How many people
- 1,200 participants
- Where
- 1 siteCanada
- Study dates
- 13 Jul 2021to 30 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with knee osteoarthritis (n=600 cannabis users and n=600 cannabis non-users); a subset of the cannabis users (n=100) and cannabis non-users (n=5) will be undergoing total knee replacement surgery.
Who may be able to join
- Age ≥25
- Able to understand and read English
- Diagnosed with knee OA or seeking treatment for knee related OA
- Experienced pain in the knee on most days for at least 3 months
Who cannot join
- Used cannabis recreationally, but not medically in the past 3 months.
- Total joint arthroplasty (TJA) within a year of informed consent.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Orthopaedic Research Office, 416-603-5800 ext. 7347, afazio@uhnresearch.ca
About this study
Official title: A Prospective Observational Study of the Relationship Between Cannabis Use, Biomarkers, Tissue Cannabinoid Levels and Clinical Outcomes in Patients With Osteoarthritis
Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability, affecting the quality of life, pain, and physical functioning of 4.6 million Canadians. About half of OA patients have limited response to primary therapy. The number of OA patients continues to rise, affecting the quality of life of those with OA. There is a dire need to develop future effective treatment options. Cannabis is a potential therapy for those with OA and may provide analgesic, anti-inflammatory, and disease modifying effects. The common barriers to use are a lack of knowledge regarding efficacy, access, and commonly used products, doses and routes of administration. No high-quality clinical trials of cannabis for OA have been conducted, leaving physicians struggling to guide and inform patients regarding symptom relief. Findings from clinical trials of cannabis for other painful conditions have been variable, perhaps due to suboptimal cannabis products and failure to consider important patient characteristics. The goal of the current study is to characterize patient- and cannabis-level factors that are associated with OA pain and address other knowledge gaps.
Read the detailed description
Given the heterogeneity of OA, it is likely that any therapeutic (or harmful) effect of cannabis will vary based on patient characteristics and levels of cannabinoids in the cannabis product used. In this study, the investigators will measure the association between patient- and cannabis-level characteristics and patient outcomes among OA patients who use cannabis to manage their MSK symptoms and those who do not. 1) A number of patient-level factors are capable of modulating the symptoms and pathology of OA. These include microRNAs (miRNAs), metabolites, and cytokines/growth factors. Alterations in these molecules have been detected in the blood of patients with OA and thus are potential biomarker candidates of disease, prognosis or even therapeutic efficacy. Biomarkers will be measured in a cohort of patients with OA to investigate whether they predict the perceived effectiveness of cannabis and whether they differ among cannabis users and non-users. In addition, the investigators will look at the correlation between biomarker(s) levels and patients' reported outcomes among cannabis users vs non-users. 2) Chondrocytes from OA joints express a wide range of cannabinoid receptors, so there is the promise that these cells could respond to cannabinoid-based medicines. In a subset of cannabis users, tissue samples from the knee will be collected to determine if the products being consumed penetrate the tissues. 3) Due to the varied chemical constituents in cannabis products, and the lack of clear understanding of the pharmacological effects of hundreds of varieties of medical cannabis, there is a need for in-depth investigations into cannabis strains produced in Canada and those consumed by patients. Research led by our group found that industry products vary from batch to batch and labeling can be inaccurate, highlighting the need for further investigation into the relationship between cannabis' chemical constituents and its clinical effect.
A total of 1200 adults with knee osteoarthritis, 600 participants who use medical cannabis to manage their symptoms and 600 who do not use it will be included. All participants will complete a set of questionnaires that will collect information about demographics, medical condition(s), current pharmaceutical pain management, and cannabis use (if any). In addition, these questionnaires will evaluate pain severity and the impact of pain on day-to-day life, anxiety, depression, and quality of life. Participants will also be required to provide a blood sample to identify biomarkers. An additional blood sample will be collected from participants who use cannabis to measure level of cannabinoids in the blood. In a subset of 105 participants (100 cannabis users and 5 cannabis non-users) undergoing total knee replacement surgery, samples of tissue discarded during surgery will be collected.
- Conditions
- Osteo Arthritis Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Patients with knee osteoarthritis who use medical cannabis to manage MSK symptoms. | |
| Cohort 2 | Patients with knee osteoarthritis who do not use medical cannabis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
MicroRNAs (Using Next Generation Sequencing)
Next Generation Sequencing will be used to identify differentially expressed circulating miRNAs in plasma samples.
Measured: Baseline
Cytokines (High-throughput Luminex-based assays)
High-throughput ELISA methodology will be used to determine levels of circulating inflammatory cytokines. Cytokines of interest include interferon (IFN)y, interleukin (IL)-1ß, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1b, tumor necrosis factor (TNF)α], and metabolic cytokines (Leptin and adiponectin).
Measured: Baseline
Pain Mediators (High-throughput Luminex-based assays)
High-throughput ELISA methodology will be used to determine levels of circulating pain mediators. Pain mediators of interest include prostaglandin(PG)E2 and nerve growth factor (NGF).
Measured: Baseline
Metabolites (Metabolomics Analyses)
A high throughput metabolomics approach will be used to determine differences in the circulating metabolites that may contribute to patient response to cannabis.
Measured: Day of Surgery
Secondary outcomes (7)
Pain Disability Index (PDI)
The PDI measures the degree to which aspects of a patient's life are disrupted by chronic pain. Patients indicate the overall impact of pain on 7 categories in their life (family/home responsibilities; recreation; social activity; occupation; sexual behaviour; self-care; life-support activities) on a scale from 0 (no disability) to 7 (worst disability). The PDI has good reliability and validity, with moderate test-retest reliability.
Measured: Baseline
Patient Health Questionnaire (PHQ-8)
The PHQ-8 is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-8 is an adaptation of PHQ-9 depression module which scores the DSM-IV criteria as "0" (not at all) to "3" (nearly every day). The item9 "How often during the past 2 weeks were you bothered by thoughts that you would be better off dead, or of hurting yourself in some way?", was deleted. The eight-item PHQ is established as a valid diagnostic and severity measure for depressive disorders in large clinical studies.
Measured: Baseline
Generalized Anxiety Disorder Assessment (GAD-7)
The GAD-7 is a measure of anxiety symptoms and a screening tool for generalized anxiety disorder (GAD). This 7-item scale assesses signs of GAD (e.g. "Feeling afraid as if something awful might happen") with response options of: (1) Not at all, (2) Several days, (3) More than half the days, (4) Nearly every day. The GAD-7 is frequently used in primary and outpatient care populations and has been found to have adequate validity and good reliability.
Measured: Baseline
Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Interference - Short Form 8a
This instrument assesses the self-reported impact of pain on daily activities, social, emotional, physical, and recreational activities. This measure assesses pain interference over the past 7 days. Each of 8 items is rated on a scale of 1-5 (1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, and 5=very much).
Measured: Baseline
Numeric Rating Scale (NRS)- Pain Intensity/Severity
This is a custom designed questionnaire containing 4 questions to assess the intensity/severity of the pain. The11-point NRS (0-10) with end points labeled "0=no pain" and "10=pain as bad as you can imagine" to measure the intensity/severity of the "worst", "least", "average" and "now" (present) pain.
Measured: Baseline
Quality of Life Scale (QoLS)
This is a custom designed questionnaire with only one item developed based on the final question of EuroQol-5D-5L to rate how "good or bad your health is TODAY" by selecting one number on the line corresponding to his/her perceived health. This 11point numeric rating scale with the endpoints labeled "0= Worst imaginable health state" and "10= Best imaginable health state."
Measured: Baseline
Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS)
The chemical composition of the cannabis samples provided by participants will be analyzed using UPLC/MS. This instrumentation will also be used to identify the level of phytocannabinoids within the blood of each cannabis user and, in a subset of 100 patients, undergoing total knee arthroplasty, joint tissue will be analyzed for the presence/absence of phytocannabinoids as well.
Measured: Day of Surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2021
- Study start13 Jul 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteo Arthritis KneeStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hance Clarke, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04971629
- Sponsor's protocol ID
- 20-5918 OA
- Status last verified
- Nov 2022
- First submitted
- 29 Jun 2021
- Last updated
- 14 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Study of the Relationship Between Cannabis Use, Biomarkers, Tissue Cannabinoid Levels and Clinical Outcomes in Patients With Osteoarthritis
- ClinicalTrials.gov ID
- NCT04971629
- Acronym / sponsor ID
- 20-5918 OA
- Conditions
- Osteo Arthritis Knee
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 13 Jul 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 21 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability, affecting the quality of life, pain, and physical functioning of 4.6 million Canadians. About half of OA patients have limited response to primary therapy. The number of OA patients continues to rise, affecting the quality of life of those with OA. There is a dire need to develop future effective treatment options. Cannabis is a potential therapy for those with OA and may provide analgesic, anti-inflammatory, and disease modifying effects. The common barriers to use are a lack of knowledge regarding efficacy, access, and commonly used products, doses and routes of administration. No high-quality clinical trials of cannabis for OA have been conducted, leaving physicians struggling to guide and inform patients regarding symptom relief. Findings from clinical trials of cannabis for other painful conditions have been variable, perhaps due to suboptimal cannabis products and failure to consider important patient characteristics. The goal of the current study is to characterize patient- and cannabis-level factors that are associated with OA pain and address other knowledge gaps.
Detailed description
Given the heterogeneity of OA, it is likely that any therapeutic (or harmful) effect of cannabis will vary based on patient characteristics and levels of cannabinoids in the cannabis product used. In this study, the investigators will measure the association between patient- and cannabis-level characteristics and patient outcomes among OA patients who use cannabis to manage their MSK symptoms and those who do not. 1) A number of patient-level factors are capable of modulating the symptoms and pathology of OA. These include microRNAs (miRNAs), metabolites, and cytokines/growth factors. Alterations in these molecules have been detected in the blood of patients with OA and thus are potential biomarker candidates of disease, prognosis or even therapeutic efficacy. Biomarkers will be measured in a cohort of patients with OA to investigate whether they predict the perceived effectiveness of cannabis and whether they differ among cannabis users and non-users. In addition, the investigators will look at the correlation between biomarker(s) levels and patients' reported outcomes among cannabis users vs non-users. 2) Chondrocytes from OA joints express a wide range of cannabinoid receptors, so there is the promise that these cells could respond to cannabinoid-based medicines. In a subset of cannabis users, tissue samples from the knee will be collected to determine if the products being consumed penetrate the tissues. 3) Due to the varied chemical constituents in cannabis products, and the lack of clear understanding of the pharmacological effects of hundreds of varieties of medical cannabis, there is a need for in-depth investigations into cannabis strains produced in Canada and those consumed by patients. Research led by our group found that industry products vary from batch to batch and labeling can be inaccurate, highlighting the need for further investigation into the relationship between cannabis' chemical constituents and its clinical effect.
A total of 1200 adults with knee osteoarthritis, 600 participants who use medical cannabis to manage their symptoms and 600 who do not use it will be included. All participants will complete a set of questionnaires that will collect information about demographics, medical condition(s), current pharmaceutical pain management, and cannabis use (if any). In addition, these questionnaires will evaluate pain severity and the impact of pain on day-to-day life, anxiety, depression, and quality of life. Participants will also be required to provide a blood sample to identify biomarkers. An additional blood sample will be collected from participants who use cannabis to measure level of cannabinoids in the blood. In a subset of 105 participants (100 cannabis users and 5 cannabis non-users) undergoing total knee replacement surgery, samples of tissue discarded during surgery will be collected.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | –Patients with knee osteoarthritis who use medical cannabis to manage MSK symptoms. |
| Cohort 2 | – | –Patients with knee osteoarthritis who do not use medical cannabis. |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with knee osteoarthritis (n=600 cannabis users and n=600 cannabis non-users); a subset of the cannabis users (n=100) and cannabis non-users (n=5) will be undergoing total knee replacement surgery.
Key inclusion criteria (4 listed)
- Age ≥25
- Able to understand and read English
- Diagnosed with knee OA or seeking treatment for knee related OA
- Experienced pain in the knee on most days for at least 3 months
Key exclusion criteria (2 listed)
- Used cannabis recreationally, but not medically in the past 3 months.
- Total joint arthroplasty (TJA) within a year of informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MicroRNAs (Using Next Generation Sequencing)
Time frame: Baseline
Next Generation Sequencing will be used to identify differentially expressed circulating miRNAs in plasma samples.
Cytokines (High-throughput Luminex-based assays)
Time frame: Baseline
High-throughput ELISA methodology will be used to determine levels of circulating inflammatory cytokines. Cytokines of interest include interferon (IFN)y, interleukin (IL)-1ß, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1b, tumor necrosis factor (TNF)α], and metabolic cytokines (Leptin and adiponectin).
Pain Mediators (High-throughput Luminex-based assays)
Time frame: Baseline
High-throughput ELISA methodology will be used to determine levels of circulating pain mediators. Pain mediators of interest include prostaglandin(PG)E2 and nerve growth factor (NGF).
Metabolites (Metabolomics Analyses)
Time frame: Day of Surgery
A high throughput metabolomics approach will be used to determine differences in the circulating metabolites that may contribute to patient response to cannabis.
7 secondary outcomes
Pain Disability Index (PDI)
Time frame: Baseline
Patient Health Questionnaire (PHQ-8)
Time frame: Baseline
Generalized Anxiety Disorder Assessment (GAD-7)
Time frame: Baseline
Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Interference - Short Form 8a
Time frame: Baseline
Numeric Rating Scale (NRS)- Pain Intensity/Severity
Time frame: Baseline
Quality of Life Scale (QoLS)
Time frame: Baseline
Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS)
Time frame: Day of Surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteo Arthritis Knee, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MicroRNAs (Using Next Generation Sequencing) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022.