Astaxanthin for Management of Inflammation in Knee Osteoarthritis

Study Overview
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Brief Summary
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Over 30 million Americans are currently affected by osteoarthritis (OA), with prevalence expected to increase 40% by 2025 as a result of the aging population and obesity epidemic. Specifically, symptomatic knee OA is a leading cause of disability. Although originally classified as non-inflammatory arthritis, recent studies suggest that a relationship exists between joint inflammation and OA. Specifically, the complex interaction between sites of local tissue damage and immune cells leads to a state of chronic joint inflammation which may play a key role in disease pathogenesis. The evidence suggesting a role of inflammation in disease progression makes anti-inflammatory agents ideal candidates for symptom management. Astaxanthin, a keto-carotenoid present in many aquatic animals, including salmon, shrimp, and lobster, is an FDA-approved nutraceutical that has powerful antioxidant and anti-inflammatory properties coupled with remarkable safety and tolerability. This prospective, blinded, randomized, placebo-controlled pilot study will evaluate the effect of astaxanthin in reducing inflammation, controlling pain, and improving physical function in patients with advanced knee osteoarthritis awaiting total joint replacement surgery. Levels of pro- and anti-inflammatory cytokines and chemokines will be measured following the completion of a daily oral regimen of astaxanthin vs. placebo. Additionally, patient-reported outcome measurements assessing physical function and pain interference will be obtained prior to and following completion of treatment allowing for a comparison between treatment groups. Study outcomes will provide evidence to support astaxanthin supplementation as a cost-effective, added strategy for symptom management in patients with advanced osteoarthritis.

Detailed Description
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Osteoarthritis (OA) is a common degenerative joint disorder that affects a significant portion of the population. Over 30 million Americans are currently affected by the disease, with prevalence expected to increase 40% by 2025 as a result of the aging population and obesity epidemic. Specifically, symptomatic knee OA is a leading cause of disability, occurring in 10% of men and 13% of women over the age of 60. Patients with symptomatic OA often experience pain, swelling, and stiffness of the knee resulting in a decrease in physical mobility which can have a drastic impact on quality of life. In addition to the significant impact on affected individuals, OA is associated with an enormous economic burden estimated at $136.8 billion annually in the US, surpassing costs of tobacco-related health effects, diabetes, and cancer. Although originally classified as non-inflammatory arthritis, recent studies suggest that a relationship exists between joint inflammation and OA. Specifically, the complex interaction between sites of local tissue damage and immune cells leads to a state of chronic joint inflammation which may play a key role in disease pathogenesis. The evidence suggesting a role of inflammation in disease progression makes anti-inflammatory agents ideal candidates for symptom management. Astaxanthin is a keto-carotenoid present in many aquatic animals, including salmon, shrimp, and lobster, that has demonstrated heightened antioxidant activity and the ability to suppress inflammation. Early evidence suggests that astaxanthin may protect against osteoarthritis in vivo, illustrating its potential as a therapeutic supplement for patients with OA. However, studies illustrating these effects in humans have yet to be conducted. This prospective, blinded, randomized, placebo-controlled pilot study will evaluate the effect of astaxanthin in reducing inflammation, controlling pain, and improving physical function in patients with advanced knee osteoarthritis awaiting total joint replacement surgery. Levels of pro- and anti-inflammatory cytokines and chemokines will be measured following the completion of a daily oral regimen of astaxanthin vs. placebo. Additionally, patient-reported outcome measurements assessing physical function and pain interference will be obtained prior to and following completion of treatment allowing for a comparison between treatment groups. Study outcomes will provide evidence to support astaxanthin supplementation as a cost-effective, added strategy for symptom management in patients with advanced osteoarthritis.

Official Title
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Effect of Astaxanthin for Pain, Function, and Inflammation in Patients With Advanced Osteoarthritis Awaiting Total Knee Replacement Surgery

Conditions
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Osteoarthritis, Knee, Osteoarthritis Knees Both, Joint Inflammation

Intervention / Treatment
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* Drug: Astaxanthin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Radiographic evidence of advanced knee osteoarthritis Knee pain Scheduled to undergo a total knee replacement Exclusion Criteria: < 18 years of age Unable to provide written consent Known allergy to fish or astaxanthin Pregnant and/or breastfeeding Received a corticosteroid injection within 3 months of initiating treatment with astaxanthin or placebo Currently taking immunosuppressants Patients with known autoimmune etiology for arthritis (e.g. Rheumatoid or Psoriatic arthritis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to receive 6 weeks of oral supplementation of either placebo or 12 mg astaxanthin prior to total knee replacement surgery.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control: Placebo Group<br>Patients will receive a 6 week daily oral supply of placebo, identical in appearance to the astaxanthin supplement. | Other: Placebo<br>* Oral placebo identical to astaxanthin supplement<br>|
| Active Comparator: Experimental: Astaxanthin Supplementation Group<br>Patients will receive a 6 week daily oral supply of 12 mg astaxanthin supplement. | Drug: Astaxanthin<br>* 12 mg oral astaxanthin supplement<br>* Other names: Dihydroxy-3,3' dioxo-4,4' bêta-carotène;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of astaxanthin on inflammatory synovial markers in patients with osteoarthritis who are scheduled to undergo a total knee replacement surgery. | We will address this by conducting a prospective, double-blinded, randomized, placebo-controlled trial in which 160 patients who have been diagnosed with advanced osteoarthritis of the knee and are scheduled to undergo a total knee replacement will randomly receive a 6-week oral daily course of either astaxanthin (12 mg) or placebo prior to surgery. Levels of pro- and anti-inflammatory cytokines and chemokines within the intra-articular synovial fluid at the time of surgery will be quantified using a bioplex 23-cytokine and chemokine assay kit in post-treatment synovial fluid samples from patients receiving either astaxanthin or placebo. | 6 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of astaxanthin on PROMIS Physical Function scores in patients with osteoarthritis who are scheduled to undergo a total knee replacement surgery. | Patient reported outcomes will be collected utilizing the Patient Reported Outcome Measurement Information Systems (PROMIS) Physical Function assessment tool. Patients receiving either astaxanthin or placebo will complete PROMIS Physical Function assessment prior to starting the oral treatment regimen and just prior to surgery, following the completion of the oral treatment regimen. As the PROMIS tool has national normative data for age, sex, and condition, collection of patient-reported outcomes in this manner will allow for comparison between patients receiving astaxanthin and patients receiving the placebo as well as the general population. An increased PROMIS Physical Function score indicates an improvement in patient-reported physical function. | 6 Weeks | 
| Effect of astaxanthin on PROMIS Pain Interference scores in patients with osteoarthritis who are scheduled to undergo a total knee replacement surgery. | Patient reported outcomes will be collected utilizing the Patient Reported Outcome Measurement Information Systems (PROMIS) Pain Interference assessment tool. Patients receiving either astaxanthin or placebo will complete the PROMIS Pain Interference assessment prior to starting the oral treatment regimen and just prior to surgery, following the completion of the oral treatment regimen. As the PROMIS tool has national normative data for age, sex, and condition, collection of patient-reported outcomes in this manner will allow for comparison between patients receiving astaxanthin and patients receiving the placebo as well as the general population. A decreased PROMIS Pain Interference score indicates an improvement in patient-reported pain interference. | 6 weeks |