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临床试验/NCT04971629
NCT04971629招募中不适用

A Prospective Observational Study of the Relationship Between Cannabis Use, Biomarkers, Tissue Cannabinoid Levels and Clinical Outcomes in Patients With Osteoarthritis

University Health Network, Toronto1 个研究点 分布在 1 个国家目标入组 1,200 人开始时间: 2021年7月13日最近更新:
适应症

试验速览

阶段
不适用
状态
招募中
入组人数
1,200
试验地点
1
主要终点
MicroRNAs (Using Next Generation Sequencing)

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Observational
观察模型
Other
时间视角
Prospective

入排标准

年龄范围
25 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 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

排除标准

  • Used cannabis recreationally, but not medically in the past 3 months.
  • Total joint arthroplasty (TJA) within a year of informed consent.

结局指标

主要结局

MicroRNAs (Using Next Generation Sequencing)

时间窗: Baseline

Next Generation Sequencing will be used to identify differentially expressed circulating miRNAs in plasma samples.

Pain Mediators (High-throughput Luminex-based assays)

时间窗: 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)

时间窗: 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.

Cytokines (High-throughput Luminex-based assays)

时间窗: 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).

次要结局

  • Pain Disability Index (PDI)(Baseline)
  • Generalized Anxiety Disorder Assessment (GAD-7)(Baseline)
  • Numeric Rating Scale (NRS)- Pain Intensity/Severity(Baseline)
  • Patient Health Questionnaire (PHQ-8)(Baseline)
  • Ultra-performance liquid chromatography/mass spectrometry (UPLC/MS)(Day of Surgery)
  • Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Interference - Short Form 8a(Baseline)
  • Quality of Life Scale (QoLS)(Baseline)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Hance Clarke

Director Pain Services, Toronto General Hospital

University Health Network, Toronto

研究点 (1)

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