Efficacy of Cannabidiol in Treatment of Pain Due to Symptomatic Osteoarthritis of the Knee: A Randomized, Double-blind, Placebo-controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- WOMAC Pain Score (WOMAC) Pain score
研究概览
简要总结
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.
详细描述
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;
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blind placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
- •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
- •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.
研究组 & 干预措施
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
干预措施: Cannabidiol Oral Product (Drug)
Placebo
In the placebo arm the placebo comparator will be administered in capsules in 3 daily doses
干预措施: Placebo (Drug)
结局指标
主要结局
WOMAC Pain Score (WOMAC) Pain score
时间窗: 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)
次要结局
- 6 min walk-test(Change of 6 min walk test from baseline to the last week of the treatment phase (Week 8))
- Use of Rescue Medication(Use of rescue mediaction during the 8 week treatment period)
- PainDETECT score(Change of PainDETECT score from baseline to the last week of the treatment phase (Week 8))
- Patient global assessment of Knee Osteoarthritis (PGA-KOA)(Change from baseline in PGA-KOA to PGA-KOA during the last week of the treatment phase (Week 8).)
- Visual Analogue Scale (VAS)(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)(Change of SF-36 score from baseline to the last week of the treatment phase (Week 8))
- WOMAC Physical function(Change from baseline in WOMAC Physical function during the last week of the treatment phase (Week 8))
研究者
Sibylle Pramhas, MD
Principal Investigator
Medical University of Vienna