This randomized, double-blind, placebo-controlled clinical study evaluates the efficacy of Native CT-II® (undenatured type II collagen) in individuals with knee osteoarthritis using a parallel design.Participants are assigned to one of three groups:

Group 1 receives Native CT-II® (40 mg daily individed doses), Group 2 receives Glucosamine HCL + Chondroitin Sulphate (2700 mg daily as acomparator), and Group 3 receives a placebo (Microcrystalline Cellulose). All participants take threecapsules after breakfast and three after dinner for 90 days . The study aims to screen approximately 142 participants

, randomizing around 114 (considering a 20% dropout rate), with a target of 90completed participants (30 per group). Osteoarthritis (OA) is a degenerative joint disorder causing pain, stiffness, and reduced mobility,primarily affecting older adults. It is a leading cause of disability, with knee OA being the mostprevalent form. The global burden of OA is rising due to aging populations and increasing obesityrates, necessitating improved treatment options. Current management focuses on symptom reliefthrough non-pharmacological (exercise, weight loss) and pharmacological (NSAIDs, analgesics)interventions, though these can have adverse effects.

Undenatured type II collagen (NCTII), derived from chicken sternum, has emerged as a potentialsupplement for joint health. It triggers an immune response that reduces inflammation and supportscartilage repair. Clinical studies show that NCTII improves joint function, pain, and quality of life,outperforming glucosamine and chondroitin with fewer side effects. A new study aims to evaluatethe efficacy of Native CT-II® in individuals with Grade II and III knee OA over 90 days, comparing itto glucosamine-chondroitin and placebo groups.

Inclusion Criteria:

• 1.Individuals ready to give voluntary, written informed consent to participate in the study.

  2.Males and females of age between 40 to 65 years (including both values) suffering from Knee Osteoarthritis under no medications.

  3.Body mass index (BMI) between 18.5 to 29.9 kg/m2 (including both values). 4.mWOMAC total score ≥ 75. 5. Individuals with knee pain having VAS score of greater than or equal to 60 mm on a 100 mm VAS scale.

  6.Radiographic evidence (lateral and anterio-posterior weight-bearing standing X-ray) of grade II/III (in 2: 1 ratio) knee Osteoarthritis (OA) for index joint (The knee with the higher pain score will be designated as the index joint for the study) based on the Kellgren and Lawrence (K&L) radiographic entry criteria for OA -

  • Grade II: Possible joint space narrowing (JSN) with definite osteophyte formation.

  • Grade III: Definite joint space narrowing, multiple osteophyte formations, some sclerosis, and possible deformity of bony ends.

    7.Individuals with a history of symptomatic knee joint pain of at least 3 months.

    8.Non-vegetarians (regardless of whether they eat chicken, fish, goat mutton, pork, beef or eggs) 9.Willing to abstain from food (fish, meat, bone broth, eggs, etc) containing Type II collagen from cartilage 48 h before all assessment visits.

    10.Willing to stop using rescue medication 48 hours prior to every assessment visits.

    11.Willing to stop the restricted dietary supplements, home-based remedies, and any other form of topical products or medications (mainly includes NSAIDs and local analgesics, DMARD, corticosteroids, etc) for knee joint pain relief or any other reason for the entire study duration.

(Note: only hot and cold fomentation will be allowed, and the participant has to record the daily frequency of fomentation in the diary. The hot/cold fomentation needs to be stopped 48 hours prior to all assessment visits.).

12.Individuals using the western toilet at home and/or workplace. 13.Willing to abstain from alcohol, caffeine, and vigorous physical activity for 24 hours before every study visit.

14.Willingness to participate and comply with the study procedures and required visits.

Exclusion Criteria:

• 1.Individuals who have been injured near the knee joint region in the past six months.

  2.Individuals with a history of knee surgery, replacement or any non-knee surgical procedures that may impact the study outcomes.

  3.Individuals who have used intra-articular injections, platelet replacement therapy, stem cell therapy and or steroids for joint health issues in the last six months.

  4.Individuals who have any other chronic disease or condition, or inflammatory disease conditions and/ or are using any medication or dietary supplements or ayurvedic medications or topical ointment/oil/gel for joint health that in the judgment of the Investigator would put the individual at unacceptable risk for an individual in the study or may interfere with evaluations in the study or noncompliance with treatment or visits.

  5.History or presence of clinically significant renal, hepatic, endocrine, biliary, gastrointestinal, pancreatic, or neurological disorders, that in the judgment of the Investigator, would interfere with the individual's ability to provide informed consent, comply with the study protocol (which might confound the interpretation of the study results), or put the individual at undue risk.

  6.History of uncontrolled hypertension and/or systolic blood pressure more than or equal to 140 mmHg and/or diastolic blood pressure more than or equal to 90 mmHg.

  7.Fasting blood glucose (FBG) more than or equal to 126 mg/dl 8.Known cases of gout and/or hyperuricemia 9.Any history or evidence of allergy to chicken, shellfish, eggs or protein products in the past.

  10.Use of collagen supplements (as dietary supplements) 11.History of bleeding disorders (e.g. Hemophilia, sickle cell anemia) 12.Other pathologic lesions on X-ray of the knee. 13.Any other condition that would prohibit completion of the exercise protocols.

  14.Individuals who have participated in a clinical study with an Investigational product within 90 days before pre-screening, and who plan to participate in another study during the study period.

  15.Not willing to abstain from the use of NSAIDs (including aspirin 50 mg/day for cardiovascular health).

  16.Pregnant or Lactating females. 17.Individuals having a history of drug or alcohol abuse. 18.Current smokers