Intermittent Hypoxia-Hyperoxia Combined With Physical Therapy for Knee Osteoarthritis

Khyber Medical University Peshawar

Status: Enrolling

Conditions: Osteo Arthritis Knee

Treatments: Procedure: Intermittent Hypoxia-Hyperoxia Therapy (IHHT); Procedure: Normoxic Air Placebo; Procedure: Conventional Physical Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06965946

KMU/DIR/CTU/2025/002

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 2 patient groups

Intermittent Hypoxia-Hyperoxia + Conventional Therapy

Experimental group

Description:

Participants in this group will receive Intermittent Hypoxia-Hyperoxia Therapy (IHHT) administered using a hypoxia generator. Each session will include 4 cycles of 5 minutes of hypoxia (13-15% O₂) followed by 2 minutes of hyperoxia (40% O₂). This therapy will be provided before each conventional physical therapy session. A total of 12 sessions (3 per week for 4 weeks) will be administered. Conventional therapy will follow the current best practices used by physical therapists in tertiary care hospitals in Peshawar.

Treatment:

Procedure: Conventional Physical Therapy

Procedure: Intermittent Hypoxia-Hyperoxia Therapy (IHHT)

Conventional Therapy with Normoxic Air

Active Comparator group

Description:

Participants in this group will receive only conventional physical therapy along with normoxic air (19.8% O₂) exposure using the same device setup to maintain blinding. They will receive 4 sessions of normoxia (5 minutes) followed by 2 minutes of normoxia as a placebo for IHHT. This will also be done prior to each of the 12 physical therapy sessions (3 per week for 4 weeks).

Treatment:

Procedure: Conventional Physical Therapy

Procedure: Normoxic Air Placebo