Tregocel® as a Dietary Supplement in Mild Knee Osteoarthritis

Study Overview
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Brief Summary
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This study is an assessment of the overall performance of participants with symptomatic mild knee OA taking Tregocel® as a dietary supplement in addition to standard of care treatment.

Detailed Description
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Tregocel® is a combination herbal product which as a dietary supplementation may help maintain proper performance of joints. Although some studies have reported beneficial effects for individual components of Tregocel®, there have been no clinical assessments of supplementation with Tregocel® as a finished product. This study will involve collection of data on Tregocel® supplementation in participants with symptomatic mild knee osteoarthritis (OA) who are already receiving standard pharmacological treatment.

Official Title
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Assessment of Performance of Participants With Mild Knee Osteoarthritis Taking Tregocel® as a Dietary Supplement Alongside Standard of Care Treatment

Conditions
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Mild Knee Osteoarthritis

Intervention / Treatment
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* Dietary Supplement: Tregocel®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Compliance with all study procedures Fulfilment of consent process Documented diagnosis of radiologically confirmed mild knee osteoarthritis with stable pain management (including patello-femoral joint, Kellgren-Lawrence classification ≤2 and clinical symptoms lasting more than 6 months prior to screening) Maximal pain score ≥30 on a 100 mm VAS at screening and confirmed at baseline, with PRN use of analgesics during run-in Completed patient diary during run-in Ambulant with ECOG score <2 Exclusion Criteria: pregnancy or breastfeeding (women) body mass index less than 18.5 kg/m^2 or more than 35.0 kg/m^2. secondary knee OA clinically apparent tense effusion of the target knee valgus/varus knee/foot deformities, ligament laxity, or meniscal instability changes in regular OA therapy during screening chronic diseases which may require treatment with systemic steroids progressive serious medical conditions severe organ dysfunction cardiac insufficiency history of gastrointestinal ulcer or bleeding. any significant medical conditions that may interfere with the study procedures, safety, compliance or overall participation in the study allergies or intolerance to any of the dietary supplement ingredients

Ages Eligible for Study
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Minimum Age: 40 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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tregocel® supplementation<br>Tregocel® coated tablets (2/day) orally for 36 weeks | Dietary Supplement: Tregocel®<br>* Coated tablet (oral)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in distance walked in 6-minutes as an indicator of AMBULATORY MOBILITY | Challenge involves subject walking unimpeded along a continuous straight line of 30 metre in distance with no incline. Distance covered will by an assistant sured with a 30 metre metric tape measure. Laps and time will be tracked manually with a digital lap counter and timer (second). Baseline values will be compared to values after supplementation to determine any change in individual performance. | Tested at Baseline (week 0) and at end of supplementation (week 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical exam parameter 1: BODY WEIGHT measurement | Body weight measure using digital scales (recorded in kilogram). | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Physical exam parameter 2: SUBJECT HEIGHT measurement | Body height measured manually using a wall tape measure (recorded in metre). Weight and height values will be used to calculate body mass index [weight (kilogram) / height (metre) ^2] | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Vital sign 1: BODY TEMPERATURE | Measured using a digital ear thermometer after 5 minutes rest, sedentary.(recorded in degree Celsius) | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Vital sign 2: BLOOD PRESSURE | Systolic and diastolic blood pressure values will be determined using an automated sphygnomanometer after 5 minutes rest, sedentary (recorded in millimeter mercury). | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Vital sign 3: PULSE RATE | Recorded using an automated sphygnomanometer after 5 minutes rest, sedentary (beats / minute) | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Arthritis self-assessment 1: Initial degree of PERCEIVED PAIN represented by manual marking on a simplified printed 100mm linear scale (during Run-in) | Subject responds to a request to report maximal pain experienced in 48 hours in target knee by pen or pencil marking along a 100mm line scale (0mm (left) = no pain; 100mm (right) = extreme pain; marks closer to right indicate more pain). Length from 0mm to mark will be measured using a 300mm ruler, to indicate the degree of maximal pain felt. No subscales are included in this assessment. Marks appearing between centre of the line and 100mm limit are considered moderate to severe (total score range = 0-100mm) | Run-in period (week -1 to week 0) | 
| Arthritis self-assessment 2: change in degree of PERCEIVED PAIN represented by manual marking on a printed 100mm linear scale (During and after supplementation) in response to WOMAC questionnaire | Subject responds to a request to report degree of pain experienced in 48 hours in target knee by pen or pencil marking along a 100mm horizontal line (0mm (left) = no pain; 100mm (right) = extreme pain; more pain = closer to right hand end of line). Length from 0mm to mark will be measured using a 300mm ruler. Report includes degree of pain felt while stationary or during normal movement (a set of 5 subscales appearing as separate lines with the same limits). Marks appearing between the centre of the line and 100mm limit are considered between moderate and severe, with more severe toward the right. Total score is a sum of the 5 subscales (range 0-500mm). WOMAC = Western Ontario and McMaster Universities Arthritis index. | Scores taken at baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Arthritis self-assessment 3: change in degree of PERCEIVED STIFFNESS represented by manual marking on a printed 100mm linear scale (During and after supplementation) in response to WOMAC questionnaire. | Subject responds to a request to report feeling of stiffness experienced in 48 hours in target knee by pen or pencil marking along a 100mm horizontal line (0mm (left) = no stiffness; 100mm (right) = extreme stiffness; more pain = closer to right hand end of line). Length from 0mm to mark will be measured using a 300mm ruler, to indicate the degree of stiffness felt at start and end of a day (a set of 2 subscales, appearing as separate lines with the same limits). Marks appearing from the centre of the line to 100mm limit are considered between moderate and severe, with more severe toward the right. Total score is a sum of the 2 subscales (range 0-200mm). | Scores taken at baseline (0 week); rescored at 12, 24, 36 and 40 weeks | 
| Arthritis self-assessment 4: change in degree of PERCEIVED DIFFICULTY WITH DAILY TASKS represented by manual marking on a printed 100mm linear scale (During and after supplementation) in response to WOMAC questionnaire. | Subject responds to a request to report difficult in performing daily tasks in 48 hours due to arthritis in target knee by pen or pencil marking along a 100mm horizontal line (0mm (left) = no pain; 100mm (right) = extreme pain; more pain = closer to right hand end of line). Length from 0mm to mark will be measured using a 300mm ruler, to indicate the degree of difficulty experienced in different domestic activities (set of 17 subscales, appearing as separate lines with the same limits). Marks appearing between the centre of the line to 100mm limit are considered between moderate and severe, with more severe toward the right. Total score is a sum of the 17 subscales (range 0-1700mm). | Scores taken at baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Change in target KNEE FLEXIBILITY assessment, based on heel-thigh distance and knee angle at maximal flexion. | Subjects will lie either supine or prone while holding their target knee statically as close to their thigh as is bearable. Distance from heal to thigh (standard tape measurement) and angle of knee (measured using a goniometer) will be recorded. | Scores taken supine and prone for both knees at baseline (week 0); rescored at 12, 24, 36 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (a) Blood cell count | Number erythrocytes leukocytes and platelets initially and changes thereafter determined using an automated blood sample analyser (number x 10^9/litre) | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (b) hemoglobin level | Hemoglobin will be measured initially and any subsequent changes determined using UV/Vis spectrometry (g/dL). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (c) sodium level | Blood sodium initially and any subsequent changes to be determined using a blood gas analyser (mM) | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (d) potassium level | Blood sodium initially and any subsequent changes to be determined using a blood gas analyser (mM) | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (e) aspartate alanine transferase level | Blood aspartate alanine transferase initially and any subsequent changes to be determined using ELISA assay (IU/L) | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (f) alanine aminotransferase | Blood alanine aminotransferase level initially and any subsequent changes to be determined using ELISA assay (IU/L) | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (g) total bilirubin level | Blood bilirubin initially and any subsequent changes to be determined using ELISA assay (IU/L). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (h) alkaline phosphatase level | Alkaline phosphatase level initially and any subsequent changes to be determined using ELISA assay (IU/L). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (i) creatine level | Creatine level initially and any subsequent changes to be determined using ELISA assay (IU/L). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (j) blood sodium | Sodium level initially and any subsequent changes to be determined using a blood gas analyser (mM). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 1: clinical HEMATOLOGY parameters (k) blood potassium | Potassium level initially and any subsequent changes to be determined using a blood gas analyser (mM). | Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (a) presence of leukocytes | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = grey, positive = increase in purple color intensity). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (b) presence of nitrites | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = yellow, positive = increase in pink color intensity). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (c) level of urobilinogen | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (normal = 0.2-1 mg/dL, yellow; raised = 2-8 mg/dL, with increasing pink intensity). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (d) presence of protein | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (none or trace amounts (quince); raised = increased darkness of green pigment) | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (e) pH | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (dual pigment assay, represented by color change from fading of orange (pH 5) to increased darkness of green pigment (pH 8.5). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (f) presence of blood | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (none = yellow; trace amounts of non-hemolysed blood (dark-green speckle discoloration on a yellow background); presence of hemolysed blood (increasing darkness of green pigment on yellow background). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (g) specific gravity (SG) | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (Dark green = 1.000, yellow-green = 1.030; increasing SG correlates with decreasing darkness of green pigment. | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (h) ketone level | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (none = beige; trace (pink = 5, increasing to large (160) mg/dL with increasing darkness of burgundy pigment) | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (i) presence of bilirubin | Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = yellow; increasing levels correlate with appearance of light brown pigment). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (j) glucose level | Urine will be dipstick tested and measured, and subsequent changes determined colorimetrically for content of glucose (absence = blue-green; presence = range form 100 (green) to > 2000 mg/dL (dark brown). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Safety assessment 2: URINALYSIS (k) presence of human chorionic gonadotrophin (hCG) | Urine will be dipstick tested and measured colorimetrically for presence of hCG (positive test = appearance of blue line on white background; negative = remains white). | Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks | 
| Determination of total usage of PRESCRIPTION ANALGESICS | Usage of any analgesics will be recorded on a daily basis by subjects using diary, which will be reviewed at clinical consultation. Total consumption will be logged at the end of the supplemention period as an indicator of changes in reliance on prescribed medications. (expressed as number of medications per day, regardless of type). | Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary supplement, arthritis, joint, complementary medicine