Osteoarthritis, Knee, Osteoarthritis Knees Both, Joint Inflammation
Conditions
Brief summary
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
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.
Interventions
DRUGAstaxanthin
12 mg oral astaxanthin supplement
OTHERPlacebo
Oral placebo identical to astaxanthin supplement
Sponsors
Prisma Health-Midlands
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participants, care providers, and investigators will not know which arm patients have been assigned to or if they receive placebo or astaxanthin.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Astaxanthin on Inflammatory Synovial Markers in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 6 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Astaxanthin on PROMIS Physical Function Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 6 Weeks | 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. The scale range is 0 to 100 with a mean of 50 and a standard deviation of 10. Higher values are associated with more or higher function. A score of 60 is one SD better than average. A score of 40 is one SD worse than average. |
| Effect of Astaxanthin on PROMIS Pain Interference Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 6 weeks | 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. The scale range is 0 to 100 with a mean of 50 and a standard deviation of 10. Higher values are associated with more or higher pain. A score of 60 is one SD worse pain than average. A score of 40 is one SD better pain than average. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control: Placebo Group Patients will receive a 6 week daily oral supply of placebo, identical in appearance to the astaxanthin supplement.
Placebo: Oral placebo identical to astaxanthin supplement | 10 |
| Experimental: Astaxanthin Supplementation Group Patients will receive a 6 week daily oral supply of 12 mg astaxanthin supplement.
Astaxanthin: 12 mg oral astaxanthin supplement | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Experimental: Astaxanthin Supplementation Group | Total | Control: Placebo Group |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 11 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 5 Participants | 4 Participants |
| Age, Continuous | 74 years STANDARD_DEVIATION 10.7 | 69 years STANDARD_DEVIATION 12 | 66 years STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment United States | 6 participants | 16 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 |
| other Total, other adverse events | 3 / 10 | 2 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 6 Weeks
Population: The synovial fluid samples were being held to be batch processed at the end of the study by an outside scientific laboratory. The study was stopped early and the cytokine and chemokines testing was not done. There are no plans to analyze these samples at present or in the future. Therefore, there are no results to report for this outcome measure which is why participants analyzed for the control and experimental groups are both 0.
Secondary
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. The scale range is 0 to 100 with a mean of 50 and a standard deviation of 10. Higher values are associated with more or higher pain. A score of 60 is one SD worse pain than average. A score of 40 is one SD better pain than average.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control: Placebo Group | Effect of Astaxanthin on PROMIS Pain Interference Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 62.0 score on a scale | Standard Error 2.2 |
| Experimental: Astaxanthin Supplementation Group | Effect of Astaxanthin on PROMIS Pain Interference Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 55.0 score on a scale | Standard Error 2.1 |
Secondary
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. The scale range is 0 to 100 with a mean of 50 and a standard deviation of 10. Higher values are associated with more or higher function. A score of 60 is one SD better than average. A score of 40 is one SD worse than average.
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control: Placebo Group | Effect of Astaxanthin on PROMIS Physical Function Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 40.3 score on a scale | Standard Error 2.1 |
| Experimental: Astaxanthin Supplementation Group | Effect of Astaxanthin on PROMIS Physical Function Scores in Patients With Osteoarthritis Who Are Scheduled to Undergo a Total Knee Replacement Surgery. | 41.9 score on a scale | Standard Error 2.3 |