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Efficacy of Cannabidiol in Knee Osteoarthritis

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ClinicalTrials.gov Identifier: NCT04607603
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Sibylle Pramhas, MD, Medical University of Vienna

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Osteo Arthritis Knee Pain, Joint Drug: Cannabidiol Oral Product Drug: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double-blind placebo-controlled
Primary Purpose: Treatment
Official Title: Efficacy of Cannabidiol in Treatment of Pain Due to Symptomatic Osteoarthritis of the Knee: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Actual Study Start Date : October 13, 2020
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis
Drug Information available for: Cannabidiol

Arm Intervention/treatment
Experimental: Cannabidiol
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
Drug: Cannabidiol Oral Product
Cannabidiol is administered in capsules. Each capsule contains 200mg of CBD administered 3 times daily to a total of 600mg per die

Placebo Comparator: Placebo
In the placebo arm the placebo comparator will be administered in capsules in 3 daily doses
Drug: Placebo
Placebo will be administered in capsules of identical appearance to CBD capsules in 3 doses per die




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. WOMAC Physical function [ Time Frame: Change from baseline in WOMAC Physical function during the last week of the treatment phase (Week 8) ]
    Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Physical function score

  2. 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). ]
    PGA-KOA as compared to placebo

  3. Use of Rescue Medication [ Time Frame: Use of rescue mediaction during the 8 week treatment period ]
    Use of rescue medication in the placebo arm compared to the CBD Arm

  4. Visual Analogue Scale (VAS) [ Time Frame: Change mean 1 week VAS-Score from baseline to the last week of the treatment phase (Week 8) ]
    Mean VAS Score during 1 week as compared to placebo

  5. 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) ]
    Health Related Quality of Life Score (SF-36) as compared to placebo

  6. 6 min walk-test [ Time Frame: Change of 6 min walk test from baseline to the last week of the treatment phase (Week 8) ]
    6 min walk-test as compared to placebo

  7. PainDETECT score [ Time Frame: Change of PainDETECT score from baseline to the last week of the treatment phase (Week 8) ]
    PainDETECT score as compared to placebo



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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
  • Mean Visual Analogue Scale (VAS) ≥ 5 during 1 week of 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.

Exclusion Criteria:

Exclusion Criteria:

  • 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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04607603


Contacts
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Contact: Sibylle Pramhas, MD +43140400 ext 41440 sibylle.pramhas@meduniwien.ac.at
Contact: Hans-Georg Kress, Prof. DDr. +4340400 ext 41440 hans-georg.kress@meduniwien.ac.at

Locations
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Austria
Department of Anesthesiology and Pain Medicine, Medical University Vienna Recruiting
Vienna, Austria, 1090
Contact: Sibylle Pramhas, MD    +43140400 ext 41440    sibylle.pramhas@meduniwien.ac.at   
Contact: Hans-Georg Kress, Prof. DDr.    +43140400 ext 41440    hans-georg.kress@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna
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Responsible Party: Sibylle Pramhas, MD, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT04607603    
Other Study ID Numbers: Version 1.4
First Posted: October 29, 2020    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Osteoarthritis
Osteoarthritis, Knee
Arthralgia
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pain
Neurologic Manifestations
Epidiolex
Anticonvulsants