Effects of Dietary Supplement on Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
This study evaluates the effects arginine on osteoarthritis (OA) in adults. Participants will be randomly divided into two groups, taking arginine and nothing, respectively. Outcomes will be evaluated by lab test results on OA joint cartilage and self-administered questionnaires. The hypothesis is that arginine can slow down or reverse OA.

Detailed Description
-----------------
Patients that meet the inclusion criteria will be approached by a member from their care team, details of this study will be explained. Verbal consent to screening will be obtained during this phone interview and recorded in the clinical trial database; patients will be screened for their eligibility, and a clinical visit will be arranged for eligible patients. Consent form and questionnaires that are commonly used to collect general health information and assess OA patients' mental and physical functions (General Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 36-Item Short Form Health Survey (SF-36)) will be mailed to eligible patients. Patients will read consent form and fill up questionnaires. Eligible patients will be reached by phone by the research assistant at a later date to obtain their verbal consent to further contact regarding participating in the study, and consent status will be recorded in the clinical trial database. Initial clinical visit: All questions and concerns will be answered by researchers, consent form will be signed by participants, research assistant, and one of the investigators, and participants will be given a copy as record. Questionnaires (baseline) will be collected. 6.5 ml of blood sample (baseline) will be collected by a qualified research nurse. Participants will be randomly divided into 2 groups, each group will receive arginine and instruction or nothing, and will take arginine or nothing for 6 months: Group I (n=50): 1.5 g of L-arginine daily. Group II (n=50): No supplement. Pre-admission clinical vist: WOMAC and SF-36 questionnaires (at 6 months of the trial) will be administered. 6.5 ml of blood sample (at 6 months of the trial) will be collected. During total joint replacement surgery, small pieces of replaced joint cartilage tissue, which are normally thrown away, will be collected. At 6 and 12 months after the surgery, participants will be reached via phone by the research assistant to complete WOMAC and SF-36 questionnaires. A blood requisition form will be mailed to participants after the last phone interview for their next scheduled routine fasting blood work; 4 ml of blood sample will be collected for the study and sent to the clinical trail lab by the blood collection centre. Lab testing will be conducted; all outcome data will be obtained and analyzed.

Official Title
-----------------
Effects of Arginine on Osteoarthritis: A Pilot Clinical Trial

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Dietary Supplement: L-arginine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Undergoing total knee replacement surgery in 6 months due to primary knee OA Must be ambulatory Must live in 50 kilometers perimeter of St. John's, capital city of Newfoundland and Labrador, Canada Exclusion Criteria: Clinical diagnosis of secondary OA or inflammatory arthritis Cod liver oil supplementation within 6 months Supplementation containing arginine within 6 months Osteoporotic fracture, previous knee surgery or arthroscopy within 6 months Use of bisphosphonates within 2 years Use of Intra-articular viscosupplementation or platelet rich plasma at any point

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arginine<br>L-arginine 1.5 g capsule by mouth, once daily for 6 months | Dietary Supplement: L-arginine<br>* L-arginine capsule<br>|
| No Intervention: No Intervention<br>no supplement for 6 months | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Gene Expressions in Osteoarthritic Knee Cartilage after 6 Months of Supplementation | After participants have been taking arginine or nothing for 6 months, and cartilage tissue has been obtained during participants' total knee replacement surgery, target gene expressions in cartilage are measured with quantitative polymerase chain reaction (qPCR). Genes include cartilage degradation enzymes - matrix metallopeptidase 13 (MMP13), cathepsin K (CTSK), cathepsin B (CTSB), and cartilage syntheses genes - aggrecan (ACAN) and type II collagen (CTXII). | up to 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OA Severity Grade of Osteoarthritic Knee Cartilage after 6 Months of Supplementation | After participants have been taking arginine or nothing for 6 months, and cartilage tissue has been obtained during participants' total knee replacement surgery, the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment protocol is used to grade OA severity of cartilage on a 7-point scale, with grade 0 as normal cartilage, 1 to 4 with articular cartilage changes only, and 5 to 6 involving subchondral bone. | up to 6 months | 
| WOMAC to Measure Changes in Joint Pain and Function between baseline and at 6 Months | WOMAC is used to collect data on participants' self reported joint pain intensity (5 items) and functional deficit (17 items) on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for pain, and 0-68 for functional deficit, and total scores for joint pain and functional deficit at 6 months are compared to baseline, respectively. | at baseline and in 6 months | 
| WOMAC to Measure Changes in Joint Pain and Function between baseline and at 6 Months Post-surgery | WOMAC is used to collect data on participants' self reported joint pain intensity (5 items) and functional deficit (17 items) on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for pain, and 0-68 for functional deficit, and total scores for joint pain and functional deficit at 6 months post surgery are compared to baseline, respectively. | at baseline and 6 months post-surgery | 
| WOMAC to Measure Changes in Joint Pain and Function between baseline and at 12 Months Post-surgery | WOMAC is used to collect data on participants' self reported joint pain intensity (5 items) and functional deficit (17 items) on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for pain, and 0-68 for functional deficit, and total scores for joint pain and functional deficit at 12 months post surgery are compared to baseline, respectively. | at baseline and 12 months post-surgery | 
| SF-36 to Measure Changes in Physical and Mental Function between baseline and at 6 Months | SF-36 is used to collect data on self reported mental and physical health state on 8 scales: physical functioning (10 items); role limitations due to physical health (4 items); role limitations due to emotional problems (3 items); energy/fatigue (4 items); emotional well-being (5 items); social functioning (2 items); pain (2 items); general health (5 items); and self reported health change within one year. All 36 scores are recoded according to Scoring Rules for the RAND 36-Item Health Survey (Version 1.0), and items in the same scale are averaged together to generate 8 scale scores, each ranging between 0-100, with higher scores representing a more favorable health state. Scores at 6 months are compared to baseline. | at baseline and in 6 months | 
| SF-36 to Measure Changes in Physical and Mental Function between baseline and at 6 Months Post-surgery | SF-36 is used to collect data on self reported mental and physical health state on 8 scales: physical functioning (10 items); role limitations due to physical health (4 items); role limitations due to emotional problems (3 items); energy/fatigue (4 items); emotional well-being (5 items); social functioning (2 items); pain (2 items); general health (5 items); and self reported health change within one year. All 36 scores are recoded according to Scoring Rules for the RAND 36-Item Health Survey (Version 1.0), and items in the same scale are averaged together to generate 8 scale scores, each ranging between 0-100, with higher scores representing a more favorable health state. Scores at 6 months post-surgery are compared to baseline. | at baseline and 6 months post-surgery | 
| SF-36 to Measure Changes in Physical and Mental Function between baseline and at 12 Months Post-surgery | SF-36 is used to collect data on self reported mental and physical health state on 8 scales: physical functioning (10 items); role limitations due to physical health (4 items); role limitations due to emotional problems (3 items); energy/fatigue (4 items); emotional well-being (5 items); social functioning (2 items); pain (2 items); general health (5 items); and self reported health change within one year. All 36 scores are recoded according to Scoring Rules for the RAND 36-Item Health Survey (Version 1.0), and items in the same scale are averaged together to generate 8 scale scores, each ranging between 0-100, with higher scores representing a more favorable health state. Scores at 12 months post-surgery are compared to baseline. | at baseline and 12 months post-surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gene expression, Molecular phenotype, Osteoarthritis severity grading