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Tregocel® as a Dietary Supplement in Mild Knee Osteoarthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03636035
Recruitment Status : Completed
First Posted : August 17, 2018
Last Update Posted : July 21, 2020
Sponsor:
Information provided by (Responsible Party):
Max Biocare Pty. Ltd.

Tracking Information
First Submitted Date  ICMJE August 8, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date July 21, 2020
Actual Study Start Date  ICMJE January 1, 2019
Actual Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
Change in distance walked in 6-minutes as an indicator of AMBULATORY MOBILITY [ Time Frame: Tested at Baseline (week 0) and at end of supplementation (week 36) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
Distance walked in 6-minutes as an indicator of AMBULATORY MOBILITY [ Time Frame: Tested at Baseline; retested at 36 weeks ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • Physical exam parameter 1: BODY WEIGHT measurement [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Body weight measure using digital scales (recorded in kilogram).
  • Physical exam parameter 2: SUBJECT HEIGHT measurement [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    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]
  • Vital sign 1: BODY TEMPERATURE [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Measured using a digital ear thermometer after 5 minutes rest, sedentary.(recorded in degree Celsius)
  • Vital sign 2: BLOOD PRESSURE [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Systolic and diastolic blood pressure values will be determined using an automated sphygnomanometer after 5 minutes rest, sedentary (recorded in millimeter mercury).
  • Vital sign 3: PULSE RATE [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Recorded using an automated sphygnomanometer after 5 minutes rest, sedentary (beats / minute)
  • Arthritis self-assessment 1: Initial degree of PERCEIVED PAIN represented by manual marking on a simplified printed 100mm linear scale (during Run-in) [ Time Frame: Run-in period (week -1 to week 0) ]
    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)
  • 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 [ Time Frame: Scores taken at baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    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.
  • 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. [ Time Frame: Scores taken at baseline (0 week); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • 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. [ Time Frame: Scores taken at baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • Change in target KNEE FLEXIBILITY assessment, based on heel-thigh distance and knee angle at maximal flexion. [ Time Frame: Scores taken supine and prone for both knees at baseline (week 0); rescored at 12, 24, 36 weeks ]
    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.
  • Safety assessment 1: clinical HEMATOLOGY parameters (a) Blood cell count [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Number erythrocytes leukocytes and platelets initially and changes thereafter determined using an automated blood sample analyser (number x 10^9/litre)
  • Safety assessment 1: clinical HEMATOLOGY parameters (b) hemoglobin level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Hemoglobin will be measured initially and any subsequent changes determined using UV/Vis spectrometry (g/dL).
  • Safety assessment 1: clinical HEMATOLOGY parameters (c) sodium level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Blood sodium initially and any subsequent changes to be determined using a blood gas analyser (mM)
  • Safety assessment 1: clinical HEMATOLOGY parameters (d) potassium level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Blood sodium initially and any subsequent changes to be determined using a blood gas analyser (mM)
  • Safety assessment 1: clinical HEMATOLOGY parameters (e) aspartate alanine transferase level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Blood aspartate alanine transferase initially and any subsequent changes to be determined using ELISA assay (IU/L)
  • Safety assessment 1: clinical HEMATOLOGY parameters (f) alanine aminotransferase [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Blood alanine aminotransferase level initially and any subsequent changes to be determined using ELISA assay (IU/L)
  • Safety assessment 1: clinical HEMATOLOGY parameters (g) total bilirubin level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Blood bilirubin initially and any subsequent changes to be determined using ELISA assay (IU/L).
  • Safety assessment 1: clinical HEMATOLOGY parameters (h) alkaline phosphatase level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Alkaline phosphatase level initially and any subsequent changes to be determined using ELISA assay (IU/L).
  • Safety assessment 1: clinical HEMATOLOGY parameters (i) creatine level [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Creatine level initially and any subsequent changes to be determined using ELISA assay (IU/L).
  • Safety assessment 1: clinical HEMATOLOGY parameters (j) blood sodium [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Sodium level initially and any subsequent changes to be determined using a blood gas analyser (mM).
  • Safety assessment 1: clinical HEMATOLOGY parameters (k) blood potassium [ Time Frame: Performed at screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Potassium level initially and any subsequent changes to be determined using a blood gas analyser (mM).
  • Safety assessment 2: URINALYSIS (a) presence of leukocytes [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = grey, positive = increase in purple color intensity).
  • Safety assessment 2: URINALYSIS (b) presence of nitrites [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = yellow, positive = increase in pink color intensity).
  • Safety assessment 2: URINALYSIS (c) level of urobilinogen [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • Safety assessment 2: URINALYSIS (d) presence of protein [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (none or trace amounts (quince); raised = increased darkness of green pigment)
  • Safety assessment 2: URINALYSIS (e) pH [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • Safety assessment 2: URINALYSIS (f) presence of blood [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • Safety assessment 2: URINALYSIS (g) specific gravity (SG) [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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.
  • Safety assessment 2: URINALYSIS (h) ketone level [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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)
  • Safety assessment 2: URINALYSIS (i) presence of bilirubin [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested initially and any subsequent changes determined colorimetrically (negative = yellow; increasing levels correlate with appearance of light brown pigment).
  • Safety assessment 2: URINALYSIS (j) glucose level [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
  • Safety assessment 2: URINALYSIS (k) presence of human chorionic gonadotrophin (hCG) [ Time Frame: Performed at screening (week -2), baseline (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested and measured colorimetrically for presence of hCG (positive test = appearance of blue line on white background; negative = remains white).
  • Determination of total usage of PRESCRIPTION ANALGESICS [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2018)
  • Physical exam parameter 1 - body weight measurement [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Body weight measure using digital scales (recorded in kilogram).
  • Physical exam parameter 2 - subject height measurement [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    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
  • Vital sign measure 1 - body temperature [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Measured using a digital ear thermometer after 5 minutes rest, sedentary.(recorded in degree Celsius)
  • Vital sign measure 2 - blood pressure [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Systolic and diastolic blood pressure values will be determined using an automated sphygnomanometer after 5 minutes rest, sedentary (recorded in millimeter mercury).
  • Vital sign measure 3 - pulse rate [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Recorded using an automated sphygnomanometer after 5 minutes rest, sedentary (beats / minute)
  • Self-assessed degree of PERCEIVED PAIN based on length marking of a simplified visual analog scale (Run-in) [ Time Frame: Run-in period (week -1 to week 0) ]
    Subject responds to a request to report maximal pain experienced in 48 hours in target knee by marking along a 100mm line scale (0mm = no pain, 100mm = extreme pain). Length from 0mm to mark will be measured using a 300mm ruler, to indicate maximal degree of pain felt.
  • Self-assessed degree of PERCEIVED PAIN based on length marking of a visual analog scale (During and after supplementation) as per Western Ontario and McMaster University (WOMAC) standardized questionnaire. [ Time Frame: Scores taken at baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Subject responds to a request to report degree of pain experienced in 48 hours in target knee by marking along a 100mm line scale (0mm = no pain, 100mm = extreme pain). Length from 0mm to mark will be measured using a 300mm ruler. Report specifically includes degree of pain felt while stationary or during normal movement.
  • Self-assessed degree of PERCEIVED STIFFNESS based on length marking of a visual analog scale (During and after supplementation) as per WOMAC standardized questionnaire. [ Time Frame: Scores taken at baseline (1 week); rescored at 12, 24, 36 and 40 weeks ]
    Subject responds to a request to report feeling of stiffness experienced in 48 hours in target knee by marking along a 100mm line scale (0mm = no stiffness, 100mm = extreme stiffness). 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.
  • Self-assessed degree of PERCEIVED DIFFICULTY WITH DAILY TASKS, based on length marking of a visual analog scale (During and after supplementation) as per WOMAC standardized questionnaire. [ Time Frame: Scores taken at baseline (1 week); rescored at 12, 24, 36 and 40 weeks ]
    Subject responds to a request to report difficult in performing daily tasks in 48 hours due to arthritis in target knee by marking along a 100mm line scale (0mm = no pain, 100mm = extreme pain). Length from 0mm to mark will be measured using a 300mm ruler, to indicate the degree of difficulty at start and end of a day.
  • Target KNEE FLEXIBILITY assessment, based on heel-thigh distance and knee angle at maximal flexion. [ Time Frame: Scores taken supine and prone for both knees at baseline (1 week); rescored at 12, 24, 36 weeks ]
    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.
  • Safety assessment 1: clinical HEMATOLOGY parameters [ Time Frame: Performed at screening (week -1), run-in (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    The following parameters will be quantitated (methods parenthesized): blood cell count - erythrocytes, leukocytes, platelets, hematocrit (automated blood analyser); hemoglobin (sprectophotometry); sodium and potassium levels (blood gas analysis); liver panel - aspartate alanine transferase; bilirubin; alkaline phosphatase; creatinine (ELISA); inflammatory status - C-reactive protein level (ELISA).
  • Safety assessment 2: urinalysis for composition and hCG level [ Time Frame: Performed at screening (week -1), run-in (Week 0); rescored at 12, 24, 36 and 40 weeks ]
    Urine will be dipstick tested and measured colorimetrically for content of leukocytes; level of nitrite, urobilinogen, protein, pH, haemoglobin, density, ketone, bilirubin and glucose. hCG identification (dispstick colorimetric indicator) will be used for women to confirm absence of a clinical pregnancy.
  • Determination of usage of prescription analgesics [ Time Frame: Screening (week -2), baseline (week 0); rescored at 12, 24, 36 and 40 weeks ]
    Type of analgesic and dosage (number of units per day) will be recorded on a daily basis by subjects using diary, which will reviewed at clinical consult. Total consumption will be logged at the end of the supplemention period as an indicator of changes in reliance on prescribed medications.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tregocel® as a Dietary Supplement in Mild Knee Osteoarthritis
Official Title  ICMJE Assessment of Performance of Participants With Mild Knee Osteoarthritis Taking Tregocel® as a Dietary Supplement Alongside Standard of Care Treatment
Brief Summary 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Mild Knee Osteoarthritis
Intervention  ICMJE Dietary Supplement: Tregocel®
Coated tablet (oral)
Study Arms  ICMJE Experimental: Tregocel® supplementation
Tregocel® coated tablets (2/day) orally for 36 weeks
Intervention: Dietary Supplement: Tregocel®
Publications * Żęgota Z, Goździk J, Głogowska-Szeląg J. IMPROVED PHYSICAL FUNCTION WITH COMPLEMENTARY USE OF A DIETARY SUPPLEMENT FOR MILD KNEE OSTEOARTHRITIS: A SUBGROUP ANALYSIS. Wiad Lek. 2021;74(9 cz 1):2128-2137.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2019)
150
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2018)
180
Actual Study Completion Date  ICMJE June 30, 2020
Actual Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03636035
Other Study ID Numbers  ICMJE MBTR01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Max Biocare Pty. Ltd.
Study Sponsor  ICMJE Max Biocare Pty. Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Krzysztof Wilczek, MD Coramed, Wroklaw
PRS Account Max Biocare Pty. Ltd.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP