Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03201614 |
| Other study ID # |
RL 04 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 22, 2018 |
| Est. completion date |
April 2022 |
Study information
| Verified date |
December 2020 |
| Source |
Regen Lab SA |
| Contact |
Valerie De Fourmestraux, PhD |
| Phone |
+41(0)21 864 01 18 |
| Email |
vdefourmestraux[@]regenlab.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hyaluronic acid (HA) is a major component of synovial fluid, to which it confers viscosity
and elasticity. It has been shown that the rheological properties of the synovial fluid
decrease in patients with osteoarthritis. Intra-articular injections of hyaluronic acid
represents a commonly used therapeutic option to relieve osteoarthritic symptoms, by exerting
a mechanical action on cartilaginous structures of the joints, thus leading to reduced pain
and improved joint function.
Platelet-rich Plasma is an autologous product prepared from the patient's own blood.
Potential benefits of platelet-rich plasma for the treatment of cartilage defects have been
suggested by many in vitro and animal studies. There are an increasing number of clinical
studies assessing the benefits of platelet rich plasma in the treatment of osteoarthritis,
showing that platelet rich plasma improves symptoms with no serious adverse events reported.
On the basis of the above, HA and platelet-rich plasma have the potential to provide added
benefits in osteoarthritis symptoms when combined, in particular in patients who have had
previous intra-articular HA treatment but who are still experiencing pain. Preliminary
evidence to this effect was presented at the 2014 Annual Congress of the French Rheumatology
Society by a group of French investigators. Renevier and Marc enrolled patients who had not
experienced adequate symptom relief from previous intra-articular HA treatment and treated
them with HA plus platelet-rich plasma prepared using A-CP HA Kit. Of the 71 patients
treated, approximately 90% were classified as responders based on the OMERACT-OARSI criteria.
The A-CP HA Kit allows for the preparation of a homogenous solution of platelet-rich plasma
and HA, intended to be injected intra-articularly for the treatment of pain in
osteoarthritis. In patients who had previous intra-articular HA treatment but who are still
experiencing pain, treatment with HA plus platelet rich plasma could provide a safe and
reproducible option before surgery.
Description:
Osteoarthritis (OA) is a degenerative disease of the joint cartilage. The evolution of this
condition is characterized by the following symptoms: pain, joint cracking/popping,
stiffness, deformity, loss of mobility and especially in the case of knee osteoarthritis,
swelling (synovial effusion).
Osteoarthritis can lead to functional impairment and deformities thereby causing degradation
of quality of life and may result in disabilities. Due to the fact that the knees and hips
are weight bearing, osteoarthritis of these joints is often more disabling for persons who
are affected by this condition.
Osteoarthritis is the most common joint disorder in the United States. Among adults 60 years
of age or older, the prevalence of symptomatic knee osteoarthritis is approximately 10% in
men and 13% in women. The number of people affected with symptomatic OA is likely to increase
due to the aging of the population and the obesity epidemic.
A healthy joint is composed of two bone ends covered by cartilage (hyaline cartilage). This
allows for shock absorption and for the bones to slide over one another with ease, thus
ensuring the joint mobility. Synovial fluid (synovium) that surrounds the cartilage acts as
lubrication and nutrition for the articular cartilage. It is mainly composed of hyaluronic
acid, a glycosaminoglycan which binds to water molecules which in turn will result in a very
viscous solution thereby giving the synovial fluid its shock absorbing properties. It has
been shown that the rheological properties of synovial fluid decrease with age and in
patients suffering from osteoarthritis, which may cause symptoms of pain and physical loss of
function as seen in gonarthrosis, for example.
Osteoarthritis has multiple causative agents, many of which are not yet fully understood.
However, a number of risk factors including age, gender, genetics, obesity, joint trauma,
certain sports or professional activities are currently known. Conventionally, there is a
distinction between so-called primary osteoarthritis, for which there is no obvious
predisposition (of unknown origin) and secondary osteoarthritis, related to previous trauma
or joint diseases. The secondary type represents the most common form of osteoarthritis.
There are many and varied possibilities for treating gonarthrosis which include both
medicated and non-medicated routes. Among these, physical therapy and an improved life style
(weight loss, use of suitable shoe inserts, regular physical activity etc.) are an essential
component in the management of knee osteoarthritis.
In terms of medication, the administration of analgesics and non-steroidal anti-inflammatory
drugs (NSAIDs) is the standard treatment. However, although they promptly act against pain
and inflammation, they only have a limited effect over time in treating the symptoms without
acting upon the cause.
Slow acting anti-rheumatic drugs, including glucosamine, chondroitin sulphate, diacerhein,
soybean and avocado unsaponifiables on the contrary have a delayed action on the pain and
joint function. Although still widely used in clinical practice for their chondroprotective
effect, they have moderate efficacy and primarily allow for the reduction of analgesic and
anti-inflammatory drug doses.
Corticoid infiltrations occupy an important place in the therapeutic range of osteoarthritis,
especially when analgesics and anti-inflammatory drugs fail to relieve an inflammatory flare.
The observed effect, however, has a limited effect over time.
Intra-articular injections of hyaluronic acid (viscosupplementation treatment) are currently
the treatment of choice in gonarthrosis as they can relieve symptoms for several months at a
time. These are designed to exert a mechanical action on cartilaginous structures of the
joints, leading to a reduction in pain and improvement in the joint function. The
effectiveness of hyaluronic acid is widely documented. Indeed, many clinical trials testing
different hyaluronic acid preparations have been carried out in humans, some of which report
results versus a saline placebo. Most of these studies conclude to the superiority of
hyaluronic acid regardless of its molecular weight.
More recently, the injections of platelet rich plasma were found to be an attractive
treatment option, due to the autologous nature of the product and its mechanism of action.
Indeed, the action of platelet rich plasma is not based on sustainable viscoelasticity of the
product, but on biological stimulation of mesenchymal stem cells (MSCs) and cartilaginous
cells. Many in vitro studies have already demonstrated the effects of isolated growth factors
on stimulation and chondrogenic differentiation of mesenchymal stem cells.
The clinical use of isolated growth factors is impossible today with regard to their mode of
production and the potential risk to human health. The autologous platelet rich plasma is the
simplest and safest solution to provide usable growth factors in a clinical setting. The
interest and potential efficacy of platelet-rich plasma in the treatment of cartilage lesions
have already been tested in vitro:
- Platelet-rich plasma increases the synthesis of proteoglycans and collagen in the
extracellular matrix of cultured intervertebral disc cells
- Platelet-rich plasma stimulates the proliferation and biosynthesis of the matrix of
articular chondrocytes in pigs
- Platelet-rich plasma increases the expression of the "cartilage oligomeric matrix
protein" (COMP) Platelet-rich plasma was superior to a standard culture medium in the
proliferation and differentiation of mesenchymal stem cells into chondrocytes At the
clinical level, a number of studies showed improved symptoms with no serious adverse
effects. When compared to hyaluronic acid injections, platelet-rich plasma treatment
demonstrated superiority in terms of reduced pain, stiffness and function.
These results suggest that platelet-rich plasma, by its specific mechanism of action, is an
effective and innovative tool in the therapeutic arsenal for the treatment of symptomatic
gonarthrosis.
On the basis o the above, it is reasonable to assume that platelet-rich plasma and hyaluronic
acid have the potential to provide added benefits in osteoarthritis when combined, in
particular in patients who have had previous intra-articular HA treatment but who are still
experiencing pain. Preliminary evidence to this effect was presented at the 2014 Annual
Congress of the French Rheumatology Society by a group of French investigators. Renevier and
Marc enrolled patients who had not experienced adequate symptom relief from previous
intra-articular HA treatment and treated them with the combination of platelet rich plasma
and HA prepared using A-CP HA Kit. Of the 71 patients treated approximately 90% were
classified as responders based on the OMERACT-OARSI criteria.
The A-CP HA Kit, manufactured by Regen Lab SA, Le Mont-sur-Lausanne, VD, Switzerland, allows
for the preparation of a homogenous solution of platelet-rich plasma and HA. The product is
intended to be injected intra-articularly for the symptomatic treatment of pain. In patients
who had previous intra-articular HA treatment but who are still experiencing pain, treatment
with HA plus platelet-rich plasma could provide a safe and reproducible option before
surgery.
The objective of this study is to investigate if a biological treatment based on a
combination of platelet-rich plasma and hyaluronic acid obtained with A-CP HA Kit is
statistically superior to HA alone, on one hand, and to a saline placebo, on the other hand,
to reduce overall knee osteoarthritis symptoms, and particularly pain, and thus improve
quality of life.
