This randomized controlled trial aims to evaluate the effectiveness of combining intermittent hypoxia-hyperoxia therapy (IHHT) with conventional physical therapy in improving pain, function, gait, balance, and general health among patients with knee osteoarthritis. The study will be conducted at the Physical Therapy Department of Rehman Medical Institute, Peshawar, Pakistan, over a period of one year.

Osteoarthritis (OA) is a prevalent chronic condition that leads to joint pain, stiffness, and impaired mobility, particularly among middle-aged and elderly populations. In Pakistan, knee OA is common and significantly impacts quality of life. Existing treatments are largely symptomatic and often insufficient, especially in resource-constrained settings.

Intermittent hypoxia-hyperoxia training (IHHT), involving alternating periods of low (13-15%) and high (40%) oxygen concentrations, has shown promise in improving physical and psychological outcomes in musculoskeletal disorders. However, evidence regarding its efficacy in knee OA is scarce, especially in low- and middle-income countries.

This trial seeks to explore whether the combination of IHHT and conventional physical therapy leads to superior improvements in clinical outcomes compared to conventional therapy alone. Participants will undergo 12 treatment sessions over 4 weeks. The primary outcome measures include pain (NPRS), function (KOOS), balance (Timed Up and Go Test), gait (Functional Gait Assessment), and inflammatory markers (CRP). The feasibility, safety, and effectiveness of this novel intervention will also be evaluated.

The study design includes assessor and participant blinding and uses rigorous methods including pre- and post-intervention assessments and statistical analysis with SPSS. Findings from this study may inform future guidelines for non-pharmacological, low-cost interventions for knee OA rehabilitation in similar contexts.

Inclusion Criteria:

• Participants aged 45 and above.
• Participants (both male and female) with knee pain for 3 months or more with any three of the following six items: age of 50 years or more, crepitations, enlarged bone, no palpable warmth, morning stiffness for less than 30 minutes, and bony tenderness.
• Patients who can walk and have a minimum score of 4 on the Numeric Pain Rating Scale.
• Participants who have intact cognition with a score of 24 and above on Mini Mini- Mental State examination.
• Participants able to walk independently for at least 45 meters in the 6-minute walk test.
• Participants having a recent X-ray (done within the past 3 months).

Exclusion Criteria:

• Patients with hip or knee arthroplasty.
• Participants with above or below knee surgery or radiating pain to the lower limb.
• Patients with history of epilepsy, pregnancy
• Diagnosed neurological condition that affects lower-limb strength or walk (e.g., stroke/ basal ganglia dysfunction/ trauma)
• Patients who refused to participate in the study or to be randomly allocated.
• Patients receiving steroids or any medicine other than that prescribed by the screening orthopaedic surgeon.

De-identified individual participant data (IPD) underlying the results reported in this trial will be made available to researchers upon reasonable request. This includes outcome measures such as pain scores, gait and balance assessments, CRP levels, and KOOS subscale results.

The data will be made available beginning 6 months after publication of the trial results and will remain available for 5 years.

Requests must be submitted to the principal investigator and will be reviewed by the institutional research committee. Access will be granted for scientifically sound proposals that align with the scope of the original study. A data use agreement will be required.

This study is double blind. Both participants and outcome assessors are blinded to group allocation. Randomization is conducted via OpenEpi, and intervention/control sessions are administered with controlled oxygen levels, but the appearance and procedures are standardized to maintain blinding.