Prolotherapy Intervention Effect in Patient With Knee Osteoarthritis

Design :

Double-blind randomized trial

Randomization :

Simple Randomization generated by an online randomizer

Sample Size :

Difference between two means of primary outcome where

• mean difference (μ 1 - μ 2 ) = 0.05
• pool variance = 0.09
• Z 1-α/2 = 1.95 with type 1 error 5%
• 1-β = 1.282 with power 90%. Yielding 16 patients for each arm

Time Period of Recruitment September 2019- August 2020

Detailed Intervention

• Intervention group : Prolotherapy given three times (Day-1, Day-29, and Day-57 )
• Comparison group : Hyaluronate given five times (Day-1, Day-8, Day-15, Day-22, and Day-29.)

Outcome Measurement :

• Cartilage Oligomeric Matrix Protein (COMP) Source of Sample : Median Cubital Vein Whole Blood Measurement : Enzyme-linked Immunoassay
• Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II) Source of Sample : 50 cc of random urine sample Measurement : Enzyme-linked Immunoassay
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for functional Outcome (self-reported assessment)

Domains :

• five elements of pain (score range 0-20),
• two for stiffness (score range 0-8),
• 17 for functional limitation (score range 0-68)

Classification :

0 - 24 : Mild 25 - 48 : Moderate 49 - 72 : Severe 73 - 96 : Extremely Severe

Statistical analysis :

• Descriptive statistic to elaborate baseline characteristic
• Assuming the baseline characteristic between groups are similar, the independent t-test will be conducted to see the differences between group, whereas Mann Whitney will be performed for non parametric data
• Difference within group (baseline and last day) will be measured by paired-t test or wilcoxon for non parametric scenario

Inclusion criteria

• The patient provides consent to be part of the research.
• The diagnosis of Knee Osteoarthritis was made based on clinical criteria/radiology American College of Rheumatology (ACR) 2012 with radiology grading according to Kellgren-Lawrence 2-3

Exclusion criteria

• The Patient has received other forms of intraarticular injection therapy.
• The patient has received Non Steroid Anti inflammation drug (NSAID) therapy for one week before the start of the intervention.
• The patient has one or more contraindications for prolotherapy (e.g., Abscess, cellulitis, or septic arthritis).

Drop Out Criteria :

• The patient has undergone a strenuous physical activity that precipitates a degree of complication (i.e., joint effusion).
• The use of NSAID within one week after the intervention.
• The patient does not adhere to the intervention.
• The patient developed or being diagnosed with osteoarthritis or other forms of inflammatory disease in other joints.