Clinical trial on old dog suffering from osteoarthritis rece

Abstract: One of the most prevalent musculoskeletal disorders in old dog is osteoarthritis. Osteoarthritis is a chronic inflammation disease mainly related to aging and genetic weakness associated to some large breed. The locomotive system of the animal is affected a way that inflammation become chronic and the dog express pain and reduce physical activities. So far, the majority of conventional treatment (meloxicam, cartrophen, derecoxib) are not permanent and pleasant to administer and received by the animal.

Since major progress are accomplish in improving nutrition to extend quality life there is more shifted from focusing exclusively on alleviating nutrient deficiencies to also stressing chronic disease prevention . Polyphenols constitute one of the most numerous and ubiquitously distributed group of plant secondary metabolites, present in all plants that have shown anti-inflammatory activities . Researcher in nutrition from Laval University in Canada, after 20 years of isolation and experimentation in livestock have find a scientifically formulate blend of polyphenols that suggest that polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects. These natural molecules express anti-inflammatory activity by modulation of pro-inflammatory gene expression such as cyclooxygenase, lipoxygenase, nitric oxide synthases and several pivotal cytokines. Numerous replicates were done in several type of livestock to statistically proof the anti-inflammatory activities of those scientifically formulate mix. Therefore a clinical trial was design to verify if old, obese and big breed of dog can benefit of this discovery. A special treat was design with high concentration of those unique formulation of polyphenols to see if sick dog will response and improve quality of life by reducing inflammation due to osteoarthritis.

A clear understanding of the molecular mechanisms of action of phenolic compounds is crucial in the valuation of these potent molecules as potential prophylactic and therapeutic nutrients.

Inflammation is a vital part of the immune system’s response to injury and infection, It is the body’s way signaling the immune system to heal and repair damaged tissues, as well as defend itself against foreign invaders, such as virus and bacteria. Without inflammation as a physical response, wound would fester, and infections could become deadly. However, if the inflammatory process goes too long or if occurs at places not needed it become problematic. Chronic inflammation has been linked to certain autoimmune disease such as rheumatoid arthritis. But healthy diet and life style can help keep inflammation under control.

There is two type of inflammation, acute and chronic inflammation. Acute inflammation occurs on direct stimulus and trigger pain and fever as part of the healing process. However chronic inflammation is considered a disturb permanent reaction that trigger long term disease such as arthritis.

One of the important anti-inflammatory mechanisms is the inhibition of eicosanoids generating enzymes including phospholipase A2, cyclooxygenase, and lipoxygenase thereby reducing the concentration of prostanoids and leukotrienes [26]. Dietary polyphenols have been found to inhibit cellular enzymes, such as PLA2, COX and LOX, in order to reduce arachidonic acid, prostaglandins and leukotrienes production, thus exerting an important anti-inflammatory action [17, 32-35]

This inhibitory action occurred through the suppression of NF-κB and MAPK pathways, respectively; studies on structure-activity relationship using different polyphenols. Growing interest has been focused on the anti-inflammatory effects of phenolic components present in polyphenols blend. In vivo studies have added further evidence to the hypothesis that consumption of polyphenols blend with increasing phenolic content, contribute to the health benefits.

Anti-inflammatory diet and supplement have become popular in recent year, however it was observed that very few diet or supplement look very efficient in a short term basis and therefore companion animal turn them self to more aggressive solution. The professional such as the veterinarianlook short term solution to help control the pain of the animal. In both cases, the solution doesn’t help to solve the problem, but to mitigate the disease. The standard treatment should always be kept in consideration by the risk of adverse effects caused by long-term toxicity of these drugs such as nonsteroidal anti-inflammatory drugs.

Pain is defined as ‘’unpleasant sensory and emotional experience associated with actual or potential tissue damage’’. Since polyphenols are involve in numerous physiological pathway related to inflammation and oxidative stress , it become more and more prevalent that they may help reducing oxidation and pain. The focus of this clinical study is to phenotypically evaluate if a precise scientifically formulate blend of polyphenols can help reduce inflammation and provide a positive response by reducing pain and improve quality of life.

Osteoarthritis in dog is a degenerative disease of the joint that undergo joint pain and stiffness. The animal express permanent discomfort and demonstrate chronic pain that limit all physical movement of the animal and therefore end up in strong inflammation and rapid degeneration.

This clinical trail is base on the premise of optimum welfare by reducing stress factors on companion animal as such as blood sampling by using numerous blood sampling already done on livestock. The physiology of inflammation is considered to be very similar in dog and other species.

Therefore the previous study in livestock demonstrated the use of this precise polyphenols blend in pain control management and stress reduction in acute stress challenge.

Polyphenols by multitargeting readily offer protections and interventions on inflammatory diseases. Thus, and innovative blend of precise polyphenols blend could be effective in the treatment of inflammation in the pathogenesis of osteoarthritis, particularly in aging dogs.

8 adult dogs (>5 years old), that weigh >20kg, male or female and with various medical history will be used in our trial, also a minimum of 8 dogs that show signs of osteoarthritis (i.e. lameness) will be used. They must not receive any drug or treatment prior and/or during the trial. Pregnant bitches or lactating bitches will be excluded for the trial.

The approach of the clinical study was to provide a specific blend of polyphenols in a treat. To do the treat we used an actual high-quality treat formula. The treat contains real meat, potato meal and other type of meal that we mix with the blend and expose to high pressure and high temperature in a standard Petfood extruder. Therefore, we were able to confirm sustainability of the active’s molecules. Three size and shape of treat were produced to see animal preference. The small star shape was the preferred of large dog.

The efficacy of the special treat will be evaluated based on:

1)Evaluation of phenotypic changes

2)Locomotive response of the companion animal.

Animals will be graded using Lameness scoring system. Lameness is defined as a deviation from the normal gait or locomotion of an animal and is most commonly due to an abnormality of the musculoskeletal system.

1) the percentage of dogs showing improvement

2) interval between the beginning of the trial and the improvement

3) the amplitude of improvement.

CLINICAL OBSERVATIONS AND MEASUREMENTS

• These elements shall be registered for each dog: name / breed/ age/ color/ sex/ weight/

• Each dog are selected base on pet owner that saw significant change in the animal behavior.

• Observation of initial improvements, physical examinations will be done by owner.

• Each dog will be assessed for its general health and presence of problem of any origin.

• Each dog that shows signs of lameness will be taken in picture.

• Any her relevant comments will be added to the file.

• Physical examination includes, without being exclusive:

- General appearance

- Musculoskeletal examination

• Any medication used and the reason for its use should be documented during the trial period and communicated as soon as possible

• Any dog can be removed or replaced during the first 2 weeks of the test (no more than 25%) due to a deficient

consumption, the reasons for which must be recorded.

The determination of the hypothesize of the Dose-response of the therapeutic dog treat were establish with 2 criteria’s:

1) Welfare issue to minimize stress on old dog by keep them in their own environment and to avoid blood sampling on a phase one.

2) Previous studies done on 33,000 pigs, 2,000 cows and 8 million broiler birds. The dose was establish in relation to body weight and metabolic rate of 5 years old big breed dog versus the evaluation of the different dose response of livestock.

Each dog will be received 125 grams treat per day by 40kg body weight for the duration of the test.

The determination of the duration of the trial was base on :

• Previous livestock data response

• Slower metabolic rate of companion animal vs livestock

• Two weeks delay response was sufficient time base on the two previous criteria.

DURATION OF THE TEST: The trial will run for a minimum of 2 weeks and will begin as soon as the dogs are fed the supplement. According to the results of the first 2 weeks, the trial may be continued or not.

Food must stay the same during the trial. Fresh water must be available at all time for every dog. Dog may be fed ad libidum or according to their nutritional needs. Any termination or modification of the food protocol must be described and reported as soon as possible

• Enclosures and bowls shall be cleaned daily (or as needed)

• Dogs should be fed twice a day and clean, fresh water shall be available at all time

• Dogs shall have a daily period of physical activity

The clinical sign scores were calculated as mean ± SD. Nonparametric 2-sample Mann-whitney procedure was used to test for the differences before and after treatment. Relative data were analyzed using the SAS version 8.0 software package; P≤ 0.01 was considered to be significant. The study design had several limitations. Because this was a clinical study the animals could not be controlled by using the same breed, sex, and age. The other limitation is the scores evaluation where it may vary in interpretation of each animals.