Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06328426 |
| Other study ID # |
Anti-osteoarthritis |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 2024 |
| Est. completion date |
December 2026 |
Study information
| Verified date |
March 2024 |
| Source |
Assiut University |
| Contact |
Adel A Gomaa, Ph.D |
| Phone |
+201009534841 |
| Email |
a.gomma[@]aun.edu.eg |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To determine the efficacy of vitamin D with omega-3 or metformin for reducing knee symptoms
and effusion synovitis in patients with symptomatic knee osteoarthritis.
Description:
Osteoarthritis (OA), one of the most common joint diseases, is characterized by fibrosis,
rhagadia, ulcers and attrition of articular cartilage due to a number of factors. The
aetiology of OA remains unclear, but its occurrence has been associated with age, obesity,
inflammation, trauma and genetic factors. The inflammation in OA is distinct from that in
rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade
inflammation, and mediated primarily by the innate immune system. Several studies showed that
inflammation triggered by factors like biomechanical stress is involved in the development of
osteoarthritis. This stimulates the release of early-stage inflammatory cytokines like
interleukin-1 beta (IL-1β), which in turn induces the activation of signaling pathways, such
as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide
3-kinase/protein kinase B. Recently, it has been observed that metabolic syndrome, which is
characterized by low-grade inflammation, can increases osteoarthritis risk. Inflammatory
cytokines are crucial for the occurrence and progression of OA. The intra-articular
proinflammatory and anti-inflammatory cytokines jointly maintain a dynamic balance, in
accordance with the physiological metabolism of articular cartilage.
The recent findings highlighting how communication between chondrocytes and macrophages via
Damage-associated molecular patterns can maintain the low-grade inflammation (LGI)in the
joint microenvironment and initiate the OA process. However, dynamic imbalance between
proinflammatory and anti-inflammatory cytokines can cause abnormal metabolism in knee
articular cartilage, which leads to deformation, loss and abnormal regeneration, and
ultimately destroys the normal structure of the knee joint. The ability of articular
cartilage to self-repair once damaged is limited, due to its inability to obtain nutrients
from blood vessels, nerves and lymphatic vessels, as well as limitations in the extracellular
matrix. Therefore, it has been suggested that the ingredients can inhibit inflammation by
reducing the expression and release of inflammatory cytokines(IL-1β , TNF-α, IL -6, IL -15,
IL -17 and IL -18 )and enhancing the expression of anti-inflammatory cytokines (IL-4, IGF,
IL-10, TGF-β and IL 1RA) which play a cartilage protective role at the gene and protein
levels. It holds promise for the development of new disease-modifying therapies for OA.
Current treatments for osteoarthritis only control symptoms and none have been approved by
the Food and Drug Administration to prevent or slow the progression of the disease. However,
some agents such as vitamin D, Omega 3 and metformin that increase anti-inflammatory
cytokines and decrease inflammatory cytokines in OA hold promise for the development of novel
disease-modifying therapies.
Vitamin D. Vitamin D seems to reduce chronic inflammation, pathophysiological involved in
endothelial dysfunction, its anti-inflammatory actions include downregulation of NF-kB and
STAT1/5-mediated signaling, with subsequent down-regulation of the production of
anti-inflammatory cytokines, such as TNF-α, IL-1, IL-2β, etc. Moreover, binding of vitamin D
to VDR results in the decrease of prostaglandin and cyclooxygenase 2 production, reduction of
metalloproteinase-9 (MMP-9) and increase in anti-inflammatory IL-10 production. In animal
studies, oral administration of vitamin D significantly reduced OA pain, inflammation,
cartilage destruction, and MMPs levels. And in IL-1β stimulated rat chondrocytes revealed
that VITD (50, 100, and 500 IU) significantly reduced the mRNA levels of MMPs, NF-κB, TNF-α,
and IL-6. Vitamin D was It also was observed that vitamin D attenuated pain and cartilage
destruction in OA Animals via enhancing autophagic flux and attenuating Inflammatory Cell
Death. Although a conclusive result has not been reached, several randomized control trials
indicated that vitamin D supplementation was possible to alleviate pain and improve joint
function in knee. Many clinical studies observed that vitamin D2 supplementation can to not
only decrease serum levels of LC3A (serum levels of autophagosome protein), inflammatory
markers, as well as oxidative stress, but also improve muscle strength and physical
performance in patients with knee OA. Other randomized controlled trials have shown that
vitamin D supplementation improves oxidative and inflammatory biomarkers, such as total
antioxidant capacity, C-reactive protein, and glutathione, but has no effect to others like
malondialdehyde and carbonyl group levels.
Omega 3 There is strong evidence that a diet rich in ω-3 fatty acid downregulates markers
related to oxidative stress, cartilage degradation, and inflammation in chondrocytes while
these markers are elevated with a higher ω-6 fatty acids. Therefore, the quality of
polyunsaturated fatty acids (PUFA) might have a distinct role in bone metabolism since
metabolites derived from ω-6 and ω-3 fatty acids can act on precursor cells of osteoblast and
adipocytes differentially. Some studies suggest that omega-3 fatty acids may have a
protective effect on joint cartilage. Cartilage degradation is a key feature of
osteoarthritis, and omega-3s may help maintain cartilage integrity by influencing the
expression of certain genes and promoting the production of molecules involved in cartilage
maintenance. Omega-3 polyunsaturated fatty acids (PUFAs) have been postulated as a potential
therapeutic treatment option for individuals with OA. Omega-3 PUFAs are recognized for their
anti-inflammatory properties, which could be beneficial in the context of OA to moderate
pro-inflammatory markers and cartilage loss.
Metformin In recent years, there has been growing interest in exploring the potential
benefits of metformin beyond its use, including its effects on various metabolic and
inflammatory conditions, such as osteoarthritis (OA). Considering the existence of metabolic
syndrome systemic low-grade inflammation in type knee OA, which accompanying aging, obesity
and diabetes, metformin could be considered as a useful and safe component of the
personalized therapeutic approach in knee OA patients. In animal studies, metformin has been
shown to have ability to the protect cartilage and subchondral bone from damage in mice with
collagenase-induced OA (CIOA). In addition, treatment with metformin lowered the level of
cartilage biomarkers (CTX-II and COMP). Other studies have suggested that metformin may have
protective effects on articular cartilage through the regulation of chondrocyte function and
the prevention of cartilage degradation. Metformin activates AMP-activated protein kinase
(AMPK), a cellular energy sensor. AMPK activation has been implicated in various cellular
processes, including inflammation and cartilage homeostasis. Some researchers suggest that
metformin's effects on AMPK activation may contribute to its potential benefits in
osteoarthritis. In a cohort study of individuals with diabetes, metformin treatment was
associated with a significant reduction in the risk of developing OA).
