Efficacy of Cannabidiol in Knee Osteoarthritis
Condition: Osteo Arthritis Knee; Pain, Joint
MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Arthralgia
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Cannabidiol Oral Product; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Cannabidiol is administered in capsules. Each capsule contains 200mg of CBD administered 3 times daily to a total of 600mg per die; Placebo will be administered in capsules of identical appearance to CBD capsules in 3 doses per die
Intervention MeSH terms: Cannabidiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment