Safety and Efficacy of JointAlive™ on the Knee-joint Function in Adults With Knee Arthritis
Condition: Osteo Arthritis Knee
MeSH terms: Arthritis; Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional

Summary: 
      Osteoarthritis (OA) is a joint disorder caused by wear and tear on the joint over time; as a
      result, the protective cartilage of the bone in the joint gradually wears down. The lifetime
      risk of developing OA in the knee, with symptoms such as pain, aching, and stiffness, is 40%
      in men and 47% in women. It is estimated that approximately 19% of Americans aged 45 and
      older are affected by knee OA. Knee OA accounts for 83% of the global burden caused by all OA
      types. Pain and stiffness in knees, a large weight-bearing joint, often leads to disability,
      which interferes with daily life activities and demands expensive medical treatments or care.
      Due to the limitations of current OA treatment methods, there is an increasing demand for
      effective and safer alternatives, such as natural health products with pain-relieving
      potential. The investigational product, JointAlive™, is a supplement designed to alleviate
      knee OA symptoms and to improve knee functionality. The present study will investigate the
      safety and efficacy of JointAlive™ in reducing knee OA symptoms and improving joint
      functionality in an otherwise healthy adult population with mild to moderate knee OA.
      JointAlive™ is a proprietary blend of Epimedium brevicornum Maxim leaves, Dioscorea nipponica
      Makino rhizome, Salvia miltoiorrhiza Bunge root and rhizome extracts
    

Detailed description: 
      Osteoarthritis (OA) is a joint disorder caused by wear and tear on the joint over time; as a
      result, the protective cartilage of the bone in the joint gradually wears down. The lifetime
      risk of developing OA in the knee, with symptoms such as pain, aching, and stiffness, is 40%
      in men and 47% in women. It is estimated that approximately 19% of Americans aged 45 and
      older are affected by knee OA. Knee OA accounts for 83% of the global burden caused by all OA
      types. Pain and stiffness in knees, a large weight-bearing joint, often leads to disability,
      which interferes with daily life activities and demands expensive medical treatments or care.
      Losina et al. reported that in the United States, the average lifetime costs for symptomatic
      knee OA management is $12,400 USD, but the cost can be higher with knee surgeries for
      advanced OA. The economic burden is expected to continue increasing in the near future due to
      the aging population and increasing prevalence of obesity in many developed countries.

      Although the exact etiology of OA is unknown, many risk factors are associated with the
      development of knee OA, such as obesity, repetitive use of joints, age, and previous knee
      injury or surgery. Multiple studies have shown a positive association between
      pro-inflammatory cytokines (e.g. tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and
      IL-6) and OA development. Cytokine-induced nuclear factor-κB (NF-κB) activation can stimulate
      articular chondrocyte catabolism and extracellular matrix degradation, leading to the
      breakdown of articular cartilage. The severity of cartilage disintegration and osteophyte (a
      bony outgrowth) formation can be identified radiographically and used for the
      Kellgren-Lawrence (KL) grading scheme. A KL score of one (doubtful narrowing of the joint
      space with possible osteophyte formation) is considered possible OA, while a score of two
      (possible narrowing of joint space with definite osteophyte formation) or three (definite
      narrowing of joint space and moderate osteophyte formation) is considered as a definite/mild
      OA.

      It is crucial to treat OA early, before it develops into more severe cases and causes
      mobility disability. The first step of OA treatment is exercise and/or physiotherapy, which
      has demonstrated long-term benefits but often difficult to maintain compliance. Once the pain
      is difficult to manage, over-the-counter medicines such as Non-Steroidal Anti-Inflammatory
      Drugs (NSAIDs) are introduced to provide relief. NSAIDs are effective in reducing pain,
      however, long-term usage requires medical supervision. Chronic NSAID use is associated with
      high incidence of adverse events such as upper gastrointestinal tract problems, kidney and
      liver injury, hypertension, and congestive heart failure. When the abovementioned treatments
      are ineffective, intra-articular injections of hyaluronic acid, cortisol, or platelet rich
      plasma are applied and proven effective, but they can be costly and may cause reactive flares
      or infections at the injection site. Surgery serves as last resort; it is a successful
      treatment for advanced OA, but it is invasive and may increase risks of infection, bleeding,
      and deep vein thrombosis. Given the limitations of current OA treatment methods, there is an
      increasing demand for effective and safer alternatives, such as natural health products with
      pain-relieving potential.

      The investigational product, JointAlive™, is a supplement designed to alleviate knee OA
      symptoms and to improve knee functionality. JointAlive™ contains extract from flowering
      plants that are endemic to China.The main bioactive component is icariin; a flavonoid
      glycoside demonstrating various antioxidant and anti-inflammatory benefits. Numerous in vitro
      cell culture studies showed that icariin has the potential to suppress inflammatory pathways
      involved in OA. In rodent OA models, joint injection of icariin for 32 and 84 days was found
      to protect the articular cartilage from degeneration.

      The present study will investigate the safety and efficacy of JointAlive™ in reducing knee OA
      symptoms and improving joint functionality in an otherwise healthy adult population with mild
      to moderate knee OA. Based on the previous studies conducted on the ingredients of this
      investigational product and their previous application in OA, participants identifying mild
      or moderate OA in a target knee will be investigated in this study. As OA is a secondary
      complication in sports injuries as well as a primary development during aging, an age range
      between 40-75 years will be considered for enrolment. The Kellgren-Lawrence grading scale
      will be used to confirm OA. As well, BMI cut offs between 18.5 and 29.9 kg/m2 will be
      considered to excluded those with complications due to obesity and the associated increase in
      concomitant medication use. To allow for pain relief, as this study involves a placebo group,
      a rescue medication will be provided. However, in order to ensure that the capture of pain in
      the target knee is unbiased, participants will be required to abstain from the rescue
      medication use for 48 hours prior to their clinic visits. Confounders due to medical history
      and concomitant medications will be ensured by several targeted exclusion criteria with the
      intent of decreasing potential confounders of the study results.
    

Intervention name(s): JointAlive™; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Combination herbal extract; Combination placebo product
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment