Evaluation of the Effect of Pro Resolve® Sports on Treatment of Patients With Symptomatic Knee Osteoarthritis

Study Overview
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Brief Summary
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The GAUDI study was a randomized, multicentre, double-blind, placebo-controlled, parallel-group pilot study conducted in 5 Spanish sites. Eligible patients were adults younger than 68 years diagnosed with symptomatic knee Osteoarthritis and pain score (VAS) ≥ 5. The primary endpoint was the change in pain from baseline to week 12. Secondary endpoints included the comparison in the change of pain, stiffness, and function according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) between groups from baseline to week 12, the assessment of the constant, intermittent, and total pain according to OMERACT-OARSI score, the changes in health-related quality of life score measured by the EUROQoL-5 questionnaire (16) between both study groups, the use of rescue, and anti-inflammatory medication, and the incidence of adverse events (AEs) during the study.

Detailed Description
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The GAUDI study was a randomized, multicentre, double-blind, placebo-controlled, parallel-group pilot study conducted in 5 Spanish centers in compliance with the World Medical Association Declaration of Helsinki, all its amendments, and national regulations. The Independent Ethic Committee of Hospital U. La Paz (Madrid, Spain) approved this study. All patients gave their written informed consent. The study duration was 24 weeks, including a screening period, a treatment period with monthly visits from the start of the study until week 12, and a follow-up visit 24 weeks after the study initiation conducted by telephone call. Participants were instructed to take two 500 mg softgels of LIPINOVA(SPM group) or olive oil placebo (placebo group) after breakfast and two after dinner during the first 6 weeks of the study. During the next 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner. Thus, the treatment period was 12 weeks. Eligible patients were adults younger than 68 years diagnosed with symptomatic knee OA (according to the American College of Rheumatology [ACR]), primary knee (OA), confirmed 2-3 Kellgren and Lawrence radiologic degree (15), and pain Visual Analogue Scale (VAS) score ≥ 5. Patients were excluded if they were allergic to fish or seafood, had an arthroscopy within the last year, had been diagnosed with secondary knee osteoarthritis, cardiopathy, pneumopathy, non-compensated nephropathy, neuropathy affecting mobility, non-compensated psychiatric disorder, fibromyalgia, and/or cognitive disorder. Patients were also excluded if they had received chondroitin sulfate, glucosamine, diacerein, corticoids infiltration, and/or platelet-rich plasma infiltration in the knee three months before the study inclusion, NSAIDs three weeks before the inclusion, and/or hyaluronic acid infiltration in the knee six months before the inclusion. Patients could not have had a drug abuse record three years before the inclusion and have participated in another clinical trial. The primary endpoint was the change in pain measured on a VAS from baseline to week 12. Secondary endpoints included the comparison in the change of pain, stiffness, and function according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) between groups from baseline to week 12, the assessment of the constant, intermittent, and total pain according to OMERACT-OARSI score, the changes in health-related quality of life score measured by the EUROQoL-5 questionnaire (16) between both study groups, the use of concomitant, rescue, and anti-inflammatory medication, and the incidence of adverse events (AEs) during the study.

Official Title
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Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Pro Resolve® Sports on Treatment of Patients With Symptomatic Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Dietary Supplement: SMP group
* Dietary Supplement: Placebo group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults younger than 68 years Diagnosis of symptomatic knee OA (according to the American College of Rheumatology [ACR]), primary knee (OA) Patients with primary knee arthrosis Patients with confirmed 2-3 Kellgren and Lawrence radiologic degree Patients with pain Visual Analogue Scale (VAS) score ≥ 5 Patients that signed informed consent Exclusion Criteria: Patients allergic to fish or seafood Patients that had an arthroscopy within the last year Patients that had been diagnosed with secondary knee osteoarthritis Patients with concomitant illnesses such as cardiopathy, pneumopathy, non-compensated nephropathy, neuropathy affecting mobility, non-compensated psychiatric disorder, fibromyalgia, and/or cognitive disorder Patients that have received NSAIDs during last 3 weeks previous to join the study Patients that hace received chondroitin sulfate, glucosamine, diacerein, corticoids infiltration, and/or platelet-rich plasma infiltration in the knee three months before the study inclusion Patients that have had a drug abuse record three years before the inclusion Patients that have had a drug abuse record three years before the inclusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 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: randomized, multicentre, double-blind, placebo-controlled, parallel-group pilot study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>In placebo group, participants were instructed to take two 500 mg olive oil placebo (placebo group) after breakfast and two after dinner during the first 6 weeks of the study. During the next 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner. Thus, the treatment period was 12 weeks | Dietary Supplement: Placebo group<br>* Participants were instructed to take two 500 mg softgels of olive oil placebo after breakfast and two after dinner during the first 6 weeks of the study. During the next 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner. Thus, the treatment period was 12 weeks<br>|
| Experimental: Specialized pro-resolving mediators (SMP) group<br>In SPM group, Participants were instructed to take two 500 mg softgels of LIPINOVA after breakfast and two after dinner during the first 6 weeks of the study. During the next 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner. Thus, the treatment period was 12 weeks | Dietary Supplement: SMP group<br>* Participants were instructed to take two 500 mg softgels of LIPINOVA(SPM group) after breakfast and two after dinner during the first 6 weeks of the study. During the next 6 weeks, participants were instructed to take one softgel after breakfast and one after dinner. Thus, the treatment period was 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain | Change in pain measured on a visual analogic scale (VAS) (intragroup). Min: 0 (no pain) max: 10 (the worst pain possible) | Basal and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain (between groups) assessed by Visual Analogic Scale. Min: 0 (no pain) max: 10 (the worst pain possible) | Change in pain (between groups) | Basal and 12 weeks | 
| Use of Rescue medication and patient drop-outs | Percentage of patients that drops-out the study and percentage of patients that need to use rescue medication during the study | Basal and 12 weeks | 
| Change in functionality assessed by WOMAC (Eastern Ontario McMaster Universities Osteoarthritis Index) score | Changes in functionality using WOMAC score. Min: 0 (better), max: 96 (worse) | Basal and 12 weeks | 
| Safety of study product, assessed as percentage of patients suffering adverse events related to study product | % of adverse events related to study product | 12 weeks | 
| Changes in pain assessed as changes in OMERACT-OARSI score | Changes in OMERACT-OARSI score. Min: 0 (better), max 44 (worse) | Basal and 12 weeks | 
| Quality of life of patients assessed as changes in EQ-5D-5L score | Changes in Quality of life (EQ-5D). Visual analogue scale (quantitative): min: 0 (worse), max: 100 (better). qualitative variables: mobility, self-care, usual activities, pain/discomfort, anxiety/depression Min: 1 (better); max: 5 (worse) | Basal and 12 weeks | 
| Inflammatory biomarkers: C-reactive protein (CRP) | Changes in Inflammatory biomarkers: CRP | Basal and 12 weeks | 
| Inflammatory biomarkers: Interleukin -1 (IL-1) | Changes in Inflammatory biomarkers: IL-1 | Basal and 12 weeks | 
| Inflammatory biomarkers: Interleukin-6 (IL-6), | Changes in Inflammatory biomarkers: IL-6 | Basal and 12 weeks | 
| Inflammatory biomarkers: Interleukin-8 (IL-8) | Changes in Inflammatory biomarkers: IL-8 | Basal and 12 weeks | 
| Inflammatory biomarkers: Tumoral Necrosis Factor -α (TNF-α) | Changes in Inflammatory biomarkers: TNF-α | Basal and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPMs, Resolvins, Osteoarthritis, Pain, Quality of life