The Marigot Osteoarthritis Nutritional Intervention (MOANi) Trial
The Marigot Osteoarthritis Nutritional Intervention (MOANi) Trial
The purpose of the study is to test 30 individuals with mild-moderate knee joint
 osteoarthritis to investigate whether the combination of Aquamin (a calcium-rich marine
 multi-mineral) and a polyphenol-rich pine bark extract (Enzogenol), when taken as a food
 supplement for 3 months has comparable or superior benefits to glucosamine sulphate in
 patients with painful knee osteoarthritis (KOA). From here on in we refer to Aquamin's
 combination product as Aquamin-plus. The main outcome measure is a reduction in pain.

 Provision of data that demonstrate preliminary equivalency or superiority to current,
 non-pharmaceutical options such as glucosamine will broaden consumer choice, and provide them
 with an option that is supported by science, rather than marketing alone.

 The hypothesis of the study is that the consumption of Aquamin-plus will have comparable
 effects on reducing pain in individuals with Knee Joint OA to glucosamine.
This project will be a double blinded randomized cross-over control (pilot) trial that will
 investigate whether the combination of Aquamin (a calcium-rich marine multi-mineral) and a
 polyphenol-rich pine bark extract (Enzogenol), when taken as a food supplement for 3 months
 (12 weeks) has comparable or superior benefits to glucosamine sulphate in patients with
 painful knee osteoarthritis (KOA). From here on in we refer to Aquamin's combination product
 as Aquamin-plus. The main outcome measure is a reduction in pain (WOMAC index) and improve
 physical function (6MWD and TUG).

 The hypothesis of the study is that the consumption of Aquamin-plus for a period of 3 months
 will have comparable or superior effects on to glucosamine sulphate in reducing pain and
 improving physical function in individuals with KOA.

 According to the Food and Drug Administration et al. osteoarthritis (OA) can be defined as a
 serious disease or condition because, among other aspects, it is "…associated with morbidity
 that has substantial impact on day-to-day functioning…" . Furthermore, the current
 Osteoarthritis Research Society International (OARSI) definition of OA has been proposed as,
 "OA is a disorder involving movable joints characterized by cell stress and extracellular
 matrix degradation initiated by micro- and macro-injury that activates maladaptive repair
 responses including pro-inflammatory pathways of innate immunity. The disease manifests first
 as a molecular derangement (abnormal joint tissue metabolism) followed by anatomic, and/or
 physiologic derangements (characterized by cartilage degradation, bone remodeling, osteophyte
 formation, joint inflammation and loss of normal joint function), that can culminate in
 illness"

 The condition can be characterized as a branch of rheumatic disease that is a progressive
 condition of synovial joints and is caused by the failure of a joint to repair following
 damage. This damage may have been caused by stresses due to an abnormality in the articular
 cartilage, subchondral bone, ligaments, menisci, periarticular muscles, peripheral nerves or
 synovium. Failure of these normal biological processes leads to breakdown of cartilage and
 bone and is characterized by symptoms of pain, stiffness, functional disability and can and
 lead to negative effects on fatigue, mood, sleep and overall quality of life. OA has the
 highest frequency of all rheumatic diseases and is one of the most prevalent chronic diseases
 in the modern day. According to the Global Burden of Disease (GBD) study, progressive ageing
 of the population could make OA the ninth cause of disability-adjusted life years (DALYs) in
 developed countries by the year 2020, with KOA accounting for 83% of the total OA burden.

 Investigations into the heritability of OA have identified some interesting results. In a
 British twin cohort, the genetic contribution to radiographically defined hip and KOA was
 estimated to 39-65% in women with a Danish twin studies finding similar variance in hip
 arthroplasty due to OA (47%) but only 18% for knee arthroplasty due to OA. However, more
 recent data from a larger cohort (n = 9058) showed a heritability of 73% and 45% in hip and
 knee arthroplasty, respectively. Interestingly, identified that while hip OA associated
 arthroplasty remains highly heritable regardless of environmental factors, while the genetic
 component of KOA (for arthroplasty) was significantly modifiable with increasing BMI. These
 data show the requirement for clinical interventions to focus on symptomatic KOA,
 particularly considering the exponentially increasing BMI and obesity in the western world.

 Data from The Irish Longitudinal Study on Ageing (TILDA) show that approximately 13%
 (women-17.3%, men-9.4%; self-reported) of Irish residence over the age of 50 suffer from
 symptomatic OA, with 19.2% of those reporting symptomatic KOA. These are similar to data from
 Arthritis Research UK showing an 18% prevalence of patients visiting a general practitioner
 presenting with symptoms of KOA. Moreover, these reported incidence rates are estimated to
 raise in tandem with population age (Arthritis Research UK, 2013). In fact, the prevalence of
 KOA in the US is 25% and increases by 2% each year, likely due to the aging population (as in
 the UK) and raising obesity rate, with a lifetime risk of symptomatic KOA as high as 60.5 %
 in obese individuals.

 Joint pain is the most common complaint among those who seek medical care for OA and as a
 result of OA pain 80% of individuals with have some degree of movement limitation, 25% cannot
 perform major activities of daily living and 11% of adults with KOA need help with personal
 care. Consequentially, OA can lead to negative effects on quality of life, mood, fatigue and
 sleep. Interestingly, poor sleep occurs in ~70% of older individuals with OA and is linked
 with fatigue, which in turn is associated with a greater fall risk in the elderly and
 identifies fatigue as a further concern, in addition to joint instability, of fall-related
 complications.

 OA is a progressive condition with no cure, however treatments do exist aimed at reducing
 symptoms and slowing progression of the disease. This in turn will improve mobility, quality
 of life and leads to a reduction in the need joint replacement surgery in the long-term and
 consequently reduces the demand on healthcare resource. Non-steroidal anti-inflammatory drugs
 (NSAID) are the traditional approach for clinical management of mild-to-moderate OA symptoms,
 however NSAIDs have been associated with potentially harmful side effects such as
 gastrointestinal complications, renal disturbances and cardiovascular events. Therefore,
 non-pharmaceutical alternatives have been developed such as glucosamine compounds, however
 the reported efficacy for reducing OA symptoms varies. Nonetheless, while glucosamine
 compounds have a lower risk of adverse effects compared to NSAIDs and other symptomatic
 slow-acting drugs for OA (SYSADOA), glucosamine compounds show higher risk of adverse side
 effects than placebo and as such alternatives should be sought. Further to possible adverse
 health effects, NSAIDs and SYASDOAs are costly and greatly affect the socioeconomic health of
 patients with OA. A recent meta-analysis of global generalized OA has shown that the
 individual annual incremental healthcare costs ranged from €705 to €19,715 and concluded that
 the social cost of OA could be between 0.25% and 0.50% of a country's GDP. More specifically,
 the individual cost of KOA (both social healthcare and private) can range from €528 to €11293
 depending of severity. In fact, Hunter et al. recently called for urgent action to focus
 attention on opportunities to reduce the individual and socioeconomic burden of OA.

 Glucosamine supplementation for the treatment of OA and OA related phenotypes spans many
 decades, with the first (to the authors' knowledge) patent filled in 1969 and research on
 human derived glucosamine published long before. The earliest identifiable mention (to the
 authors' knowledge) of Aqumin is from the late 90's with a patent, containing Aqumin, filled
 for human consumption in 2003, "Algae-based food supplement". Therefore, there is a
 significant advantage for glucosamine in the accumulation of large high quality studies into
 its therapeutic effects. Nonetheless, the few small pilot studies concerned with the
 therapeutic effects of Aquamin supplementation show promising results in comparison to both
 placebo and Glucosamine formulas. In fact, for some important OA phenotypes, Aquamin performs
 better, particularly in the reduction of NSAID use. While the proposed mechanisms of action
 differ considerable between the two supplements, inflammatory reduction occurs because of
 both. Currently, there have been no long-term trials concerned with the efficacy of Aquamin
 in the reduction of KOA related joint structural decline however, because Aquamin reduces
 inflammatory markers of KOA, albeit in only one small human study, it is possible that
 Aquamin might improve joint structural decline and KOA prognosis through possibly reducing
 joint tissue damage.

 This project will be a double blinded randomized cross-over control trial with a sample size
 of 30 participants (based off a sample size calculation detailed below). The project will
 investigate two supplements on their effects on self-reported pain, quality of life, knee
 extensor/flexor strength, knee extensor/flexor myoelectric activity, functional mobility and
 biomarkers associated with inflammation. The participants will first be assessed for baseline
 measurements of the outcome measures mentioned above. They will then be randomly allocated to
 either group A or B and will take either supplement A or B for a period of 12 weeks.
 Following this there will be follow up assessments of the same outcome measures. This will be
 followed by a 4-week washout period prior to each subjects' baseline measures being
 reassessed and each participant allocated the 'other' supplement. After 12 weeks'
 supplementation, the subjects will then be retested for a final time.

 An a priori sample size calculation indicated a total of 29 patients was required to enter
 this two-treatment crossover study to assess the primary outcomes. The probability is 80
 percent that the study will detect a treatment difference at a two-sided 0.05 significance
 level, if the true difference between treatments is 12.000 units. This is based on the
 assumption that the within-patient standard deviation of the response variable is 15.62."
Inclusion Criteria:

 The project will focus on patients with a diagnosis of a mild-moderate KOA (level 1-3
 Kellgren and Lawrence and WOMAC in the lower two quartiles), in the target knee, (Frestedt
 et al., 2008) and a BMI between 20 and 30 kg/m2.

 Exclusion Criteria:

 [1] rheumatoid arthritis [2] gout [3] pseudo gout [4] Paget's disease [5] seizure disorder
 [6] insulin dependent diabetes mellitus [7] uncontrolled hypertension [8] unstable
 cardiovascular disease [9] active hepatic or renal disease [10] active cancer and/or HIV
 infection, involved in other clinical trial or experimental treatments in the past 3
 months; pregnant, lactating, or at risk of becoming pregnant; intramuscular/systemic
 corticosteroid injection within 4 weeks; intra-articular corticosteroid injection within 2
 months; or inter-articular hyaluronic acid injection within 4 months prior to enrollment.