Osteo Arthritis KneePhase 4NCT04607603
Efficacy of Cannabidiol in Knee Osteoarthritis
A Phase 4 study testing Cannabidiol Oral Product in people with Osteo Arthritis Knee and Pain, Joint, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited. Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Osteo Arthritis Knee, Pain, Joint
- What is being tested?
- Cannabidiol Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteAustria
- Study dates
- 13 Oct 2020to 29 Mar 2022
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be willing and able to give informed consent for participation in the study
- Age 18-80 years
- Knee Pain
- WOMAC Pain Subscale ≥ 5 during screening
- Fulfilment of the clinical criteria of the American College of Rheumatology for knee OA 13
- X-ray or MRI confirmation of knee osteoarthritis
- All medications or interventions for pain due to knee osteoarthritis must have been stable for two weeks prior to screening and patient is willing to maintain a stable regimen throughout the study.
Who cannot join
- Current mood disorder (dysthymia, bipolar mood disorder)
- Major Depression > 12 months (Beck Depression Inventory Score ≥ 18)
- History of a psychoactive substance use disorder within the preceding 12 months
- Major coexisting medical illness (e.g. severe heart failure, pulmonary hypertension, renal insufficiency)
- Glaucoma
- Acute myocardial infarction
Show all 26Show fewer
- Uncontrolled hypertension
- History of convulsion
- Pregnancy; women of childbearing age will be required to use contraceptives during the duration of the study. Furthermore a pregnancy test will be performed prior to the beginning of the study and once a month during the study period.
- Breast feeding
- Participation in a clinical trial in the 3 weeks preceding the study
- Allergy to study medication
- Recent intra-articular corticosteroid or hyaluronic acid injection in the knee joint. Patients must be willing to abstain from such interventions during the entire study
- Use of the following medication:
- opioids except for tramadol,
- benzodiazepines other than indicated at low doses for sleep disorders
- NSAID
- Corticosteroids
- Impaired kidney function (Creatinine > 1.5mg/dl)
- Patient has significantly impaired hepatic function defined as any of the following:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN).
- ALT or AST >3 × ULN and (total bilirubin [TBL] >2 × ULN or international normalized ratio [INR] >1.5).
- ALT or AST >3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash,and/or eosinophilia (>5%).
- Patient is currently using or has in the past used recreational or medicinal cannabis or synthetic cannabinoid based medications within 3 months prior to study entry
- Patient is unwilling to abstain from using recreational or medicinal cannabis, or synthetic cannabinoid based medications during the study
- Patients who are not able to understand the study measures and are not able to complete pain assessment forms.
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Anesthesiology and Pain Medicine, Medical University Vienna
Vienna, 1090
About this study
Official title: Efficacy of Cannabidiol in Treatment of Pain Due to Symptomatic Osteoarthritis of the Knee: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited.
Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.
Cannabidiol has anti-inflammatory and analgesic properties in animal models. We therefore propose a randomised, double-blind, placebo-controlled clinical trial to investigate the potential efficacy of cannabidiol in painful symptomatic OA of the knee.
Read the detailed description
Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited. The Osteoarthritis Research Society International recommends paracetamol, duloxetine, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors (anti-inflammatory substances) in patients without relevant concomitant diseases. In individuals with relevant concomitant diseases (diabetes, advanced age, high blood pressure, cardiovascular diseases, renal failure, gastrointestinal complications, depression, obesity), the recommendation for paracetamol, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors changes to 'inappropriate'.
In individuals with high co-morbidity risk (history of GI-bleeding, myocardial infarction, chronic renal failure) NSAIDs and oral COX-2 inhibitors are evaluated as inappropriate.
Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.
Design
The planned study will be randomised, double-blind and placebo-controlled. 2 parallel groups will be investigated. One group will receive placebo, the other will receive 600mg cannabidiol per os during the treatment phase. The total study duration will be 13 weeks (2 weeks screening;
1 week titration phase; 7 weeks maintenance phase; 1 week tapering phase; 2 weeks follow-up) Main objective of the study will be to compare the change in the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain Index from baseline to the last week of the maintenance phase between the placebo and verum groups. The WOMAC Osteoarthritis Index is a validated patient questionnaire to assess symptoms and physical functional limitations in everyday life.
Secondary objectives include comparing the change in the WOMAC Function Index, the Global Patient Assessment of Gonarthrosis and the VAS Score. The planned number of participants is 86 (43 patients per group)
Measures/procedure After a 2-week screening phase, patients are randomised to a 1:1 placebo:verum after written consent. During the screening all patients are adjusted to a basic medication of 3 times 1g paracetamol/day. In the cannabidiol arm, titration is carried out within one week to the target dose of 600mg per day. This dosage is maintained for 7 weeks. This is followed by a balancing phase of 1 week. A follow-up is carried out 2 weeks after the maintenance phase is finished.
4 study visits are associated with blood sampling (safety laboratory) and physical examination and the completion of questionnaires and are carried out at our pain outpatient clinic. The remaining weekly visits are carried out by telephone.
During the entire duration of the study, patients are allowed the rescue medication of Tramadol 50mg up to 6/day.
- Conditions
- Osteo Arthritis Knee, Pain, Joint
- Being tested
- Cannabidiol Oral Product, Placebo
- Medical subject headings
- Arthralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cannabidiol Oral ProductDrug
Cannabidiol is administered in capsules. Each capsule contains 200mg of CBD administered 3 times daily to a total of 600mg per die
PlaceboDrug
Placebo will be administered in capsules of identical appearance to CBD capsules in 3 doses per die
| Study group | Role | What they receive |
|---|---|---|
| Cannabidiol | Experimental | In the Cannabidiol (CBD) arm CBD will be titrated up to 600 mg per die (titration 1 week) in capsules (3 daily doses) and maintained at 600mg per die (3 daily doses) for 7 weeks Receives: Drug: Cannabidiol Oral Product |
| Placebo | Placebo comparator | In the placebo arm the placebo comparator will be administered in capsules in 3 daily doses Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
WOMAC Pain Score (WOMAC) Pain score
Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain Score Minimum=0 (best outcome) Maximum=10 (worst outcome)
Measured: Change from baseline in WOMAC-Pain Index to the last week of the treatment phase (Week 8)
Secondary outcomes (7)
WOMAC Physical function
Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Physical function score Minimum=0 (best outcome) Maximum=10 (worst outcome)
Measured: Change from baseline in WOMAC Physical function during the last week of the treatment phase (Week 8)
Patient global assessment of Knee Osteoarthritis (PGA-KOA)
PGA-KOA as compared to placebo
Measured: Change from baseline in PGA-KOA to PGA-KOA during the last week of the treatment phase (Week 8).
Use of Rescue Medication
Use of rescue medication in the placebo arm compared to the CBD Arm
Measured: Use of rescue mediaction during the 8 week treatment period
Visual Analogue Scale (VAS)
Mean VAS Score during 1 week as compared to placebo Minimum=0 (best outcome) Maximum=10 (worst outcome)
Measured: Change mean 1 week VAS-Score from baseline to the last week of the treatment phase (Week 8)
Health Related Quality of Life Score (SF-36)
Health Related Quality of Life Score (SF-36) as compared to placebo Minimum=0 (lowest level of health) Maximum=100 (highest level of health)
Measured: Change of SF-36 score from baseline to the last week of the treatment phase (Week 8)
6 min walk-test
6 min walk-test as compared to placebo
Measured: Change of 6 min walk test from baseline to the last week of the treatment phase (Week 8)
PainDETECT score
PainDETECT score as compared to placebo Minimum= 0 (least likelihood neuropathic pain) Maximum=38 (highest likelihood neuropathic pain)
Measured: Change of PainDETECT score from baseline to the last week of the treatment phase (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start13 Oct 2020
- Primary completion17 Feb 2022
- Study completion29 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteo Arthritis KneeStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sibylle Pramhas, MD, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04607603
- Sponsor's protocol ID
- Version 1.4
- Status last verified
- Oct 2022
- First submitted
- 22 Oct 2020
- Last updated
- 5 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pramhas S, Thalhammer T, Terner S, Pickelsberger D, Gleiss A, Sator S, Kress HG. Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Lancet Reg Health Eur. 2023 Nov 10;35:100777. doi: 10.1016/j.lanepe.2023.100777. eCollection 2023 Dec.
PubMed 38033459
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Cannabidiol in Treatment of Pain Due to Symptomatic Osteoarthritis of the Knee: A Randomized, Double-blind, Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT04607603
- Acronym / sponsor ID
- Version 1.4
- Conditions
- Osteo Arthritis Knee, Pain, Joint
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 17 Feb 2022 (actual)
- Study completion
- 29 Mar 2022 (actual)
- First posted
- 29 Oct 2020 (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.
Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited.
Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.
Cannabidiol has anti-inflammatory and analgesic properties in animal models. We therefore propose a randomised, double-blind, placebo-controlled clinical trial to investigate the potential efficacy of cannabidiol in painful symptomatic OA of the knee.
Detailed description
Painful symptomatic osteoarthritis (OA) of the knee is a very common disease, especially in older people (lifetime prevalence 9.5%). Current systemic pharmacological treatment options are limited. The Osteoarthritis Research Society International recommends paracetamol, duloxetine, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors (anti-inflammatory substances) in patients without relevant concomitant diseases. In individuals with relevant concomitant diseases (diabetes, advanced age, high blood pressure, cardiovascular diseases, renal failure, gastrointestinal complications, depression, obesity), the recommendation for paracetamol, oral non-selective non-steroidal anti-inflammatory drugs and oral COX-2 inhibitors changes to 'inappropriate'.
In individuals with high co-morbidity risk (history of GI-bleeding, myocardial infarction, chronic renal failure) NSAIDs and oral COX-2 inhibitors are evaluated as inappropriate.
Many patients presenting with knee osteoarthritis are of an advanced age and suffer from various co-morbidities. The benefit of the available systemic pharmacological treatment options in these patients can be summarized as uncertain. Therefore, the investigation of new symptomatic systemic pharmacological treatment options for knee OA is relevant. Even in patients without known contraindications, the treatment period with non-steroidal anti-inflammatory drugs should be kept short. It follows that the investigation of new potentially anti-inflammatory substances is of interest in symptomatic OA of the knee.
Design
The planned study will be randomised, double-blind and placebo-controlled. 2 parallel groups will be investigated. One group will receive placebo, the other will receive 600mg cannabidiol per os during the treatment phase. The total study duration will be 13 weeks (2 weeks screening;
1 week titration phase; 7 weeks maintenance phase; 1 week tapering phase; 2 weeks follow-up) Main objective of the study will be to compare the change in the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain Index from baseline to the last week of the maintenance phase between the placebo and verum groups. The WOMAC Osteoarthritis Index is a validated patient questionnaire to assess symptoms and physical functional limitations in everyday life.
Secondary objectives include comparing the change in the WOMAC Function Index, the Global Patient Assessment of Gonarthrosis and the VAS Score. The planned number of participants is 86 (43 patients per group)
Measures/procedure After a 2-week screening phase, patients are randomised to a 1:1 placebo:verum after written consent. During the screening all patients are adjusted to a basic medication of 3 times 1g paracetamol/day. In the cannabidiol arm, titration is carried out within one week to the target dose of 600mg per day. This dosage is maintained for 7 weeks. This is followed by a balancing phase of 1 week. A follow-up is carried out 2 weeks after the maintenance phase is finished.
4 study visits are associated with blood sampling (safety laboratory) and physical examination and the completion of questionnaires and are carried out at our pain outpatient clinic. The remaining weekly visits are carried out by telephone.
During the entire duration of the study, patients are allowed the rescue medication of Tramadol 50mg up to 6/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cannabidiol | Experimental | Drug: Cannabidiol Oral ProductIn the Cannabidiol (CBD) arm CBD will be titrated up to 600 mg per die (titration 1 week) in capsules (3 daily doses) and maintained at 600mg per die (3 daily doses) for 7 weeks |
| Placebo | Placebo comparator | Drug: PlaceboIn the placebo arm the placebo comparator will be administered in capsules in 3 daily doses |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient must be willing and able to give informed consent for participation in the study
- Age 18-80 years
- Knee Pain
- WOMAC Pain Subscale ≥ 5 during screening
- Fulfilment of the clinical criteria of the American College of Rheumatology for knee OA 13
Key exclusion criteria (26 listed)
- Current mood disorder (dysthymia, bipolar mood disorder)
- Major Depression > 12 months (Beck Depression Inventory Score ≥ 18)
- History of a psychoactive substance use disorder within the preceding 12 months
- Major coexisting medical illness (e.g. severe heart failure, pulmonary hypertension, renal insufficiency)
- Glaucoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cannabidiol Oral ProductCannabidiol is administered in capsules. Each capsule contains 200mg of CBD administered 3 times daily to a total of 600mg per die | Drug | Cannabidiol |
| PlaceboPlacebo will be administered in capsules of identical appearance to CBD capsules in 3 doses per die | Drug | Placebo |
Primary outcome
WOMAC Pain Score (WOMAC) Pain score
Time frame: Change from baseline in WOMAC-Pain Index to the last week of the treatment phase (Week 8)
Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain Score Minimum=0 (best outcome) Maximum=10 (worst outcome)
7 secondary outcomes
WOMAC Physical function
Time frame: Change from baseline in WOMAC Physical function during the last week of the treatment phase (Week 8)
Patient global assessment of Knee Osteoarthritis (PGA-KOA)
Time frame: Change from baseline in PGA-KOA to PGA-KOA during the last week of the treatment phase (Week 8).
Use of Rescue Medication
Time frame: Use of rescue mediaction during the 8 week treatment period
Visual Analogue Scale (VAS)
Time frame: Change mean 1 week VAS-Score from baseline to the last week of the treatment phase (Week 8)
Health Related Quality of Life Score (SF-36)
Time frame: Change of SF-36 score from baseline to the last week of the treatment phase (Week 8)
6 min walk-test
Time frame: Change of 6 min walk test from baseline to the last week of the treatment phase (Week 8)
PainDETECT score
Time frame: Change of PainDETECT score from baseline to the last week of the treatment phase (Week 8)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2022.
- Derived from this study: PubMed 38033459Pramhas S, Thalhammer T, Terner S, Pickelsberger D, Gleiss A, Sator S, Kress HG. Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Lancet Reg Health Eur. 2023 Nov 10;35:100777. doi: 10.1016/j.lanepe.2023.100777. eCollection 2023 Dec.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cannabidiol Oral Product in people with Osteo Arthritis Knee and Pain, Joint, run by Medical University of Vienna at 1 site in Austria.
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 7 inclusion and 26 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: finished, as of the sponsor's last update on 5 Oct 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 Austria. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
WOMAC Pain Score (WOMAC) Pain score (time frame: Change from baseline in WOMAC-Pain Index to the last week of the treatment phase (Week 8)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04607603, which also lists 1 linked publication.
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 5 Oct 2022.