Intermittent Hypoxia-Hyperoxia Combined With Physical Therapy for Knee Osteoarthritis

June 22, 2026 updated by: Khyber Medical University Peshawar

Effectiveness of Combining Intermittent Hypoxia-Hyperoxia and Conventional Physical Therapy for Patients With Knee Osteoarthritis: A Randomized Controlled Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Khyber Pakhtunkhwa
      • Peshawar, Khyber Pakhtunkhwa, Pakistan, 25000
        • Rehman Medical Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intermittent Hypoxia-Hyperoxia + Conventional Therapy
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.
Procedure: Intermittent Hypoxia-Hyperoxia Therapy (IHHT)
Participants receive 4 cycles per session of 5 minutes of hypoxia (13-15% O₂) followed by 2 minutes of hyperoxia (40% O₂) using a hypoxia generator (Olive OLV 10H). Sessions are delivered before each conventional physical therapy session, 3 times per week for 4 weeks (total 12 sessions). Participants are monitored for heart rate, blood pressure, and oxygen saturation throughout the intervention.
Other Names:
  • Olive OLV 10H Hypoxia Generator
Procedure: Conventional Physical Therapy
Participants receive individualized conventional physical therapy for knee osteoarthritis based on current clinical practices in tertiary hospitals of Peshawar. Therapy is delivered 3 times per week for 4 weeks (total 12 sessions) and includes strength training, mobility exercises, and patient education.
Active Comparator: Conventional Therapy with Normoxic Air
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).
Procedure: Conventional Physical Therapy
Participants receive individualized conventional physical therapy for knee osteoarthritis based on current clinical practices in tertiary hospitals of Peshawar. Therapy is delivered 3 times per week for 4 weeks (total 12 sessions) and includes strength training, mobility exercises, and patient education.
Procedure: Normoxic Air Placebo
Participants in the control group inhale normoxic air (19.8% O₂) using the same Olive OLV 10H hypoxia generator to maintain blinding. Each session consists of 4 cycles of 5 minutes of normoxia followed by 2 minutes of normoxia, simulating the timing of hypoxia-hyperoxia therapy. Sessions are administered prior to conventional physical therapy, 3 times per week for 4 weeks (total 12 sessions). Patients are monitored for vital signs throughout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Reduction
Time Frame: Baseline and 4 weeks (12 sessions of therapy)
Measured on the Numeric Pain Rating Scale (NPRS), which has levels ranging from 0 to 10 in severity. 0 indicates no pain, and 10 indicates severe pain. The scale is divided into 3 categories. 1-3 indicates mild pain, 4-6 indicates moderate pain, and 7-10 indicates severe pain.
Baseline and 4 weeks (12 sessions of therapy)
Functional Status - KOOS Activities of Daily Living Subscale
Time Frame: Baseline and 4 weeks
The Knee Injury and Osteoarthritis Outcome Score (KOOS) will be used to assess pain, recreation and quality of life, symptoms and stiffness, ADL and functional sports. The scores of each category will be calculated and converted to percentages (100%). 0-39% will indicate severe condition, 40- 59% will indicate moderate condition, 60-79% will indicate mild condition, and 80-100% will indicate no dysfunction.
Baseline and 4 weeks
Inflammatory Marker - C-Reactive Protein (CRP)
Time Frame: Baseline and 4 weeks
Change in serum CRP levels measured through a blood sample as a biomarker of osteoarthritis-related inflammation. CRP levels will be taken on a continuous scale.
Baseline and 4 weeks
Balance - Timed Up and Go Test (TUG)
Time Frame: Baseline and 4 weeks
Time taken (in seconds) to rise from a chair, walk 3 meters, turn, walk back, and sit down using a stop watch. A time of < or equal to 10 seconds will be considered normal, 11-20 seconds indicates good mobility with functional indipendence. > or equal to 20 seconds indicates that person needs assistance outside, 30 seconds or more indicates that person is prone to fall. MCID for time up and Go test is 2.1 seconds.
Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gait Performance - Functional Gait Assessment (FGA) Score
Time Frame: Baseline and 4 weeks
Evaluation of gait performance and stability using the FGA scale. Normal (score of 3) performances will be walking a distance of 6 meters in less than 5.5 seconds with no assistive device and no evidence of imbalance, a normal gait pattern, and not deviating more than 6 inches out of 12 12-inch walkway width. Mild impairment (score of 2) will be recorded when a person walks 6 meters with the use of an assistive device at a slower speed and mild gait deviation (15.24-25.4 cm) outside 12 12-inch walkway. Participants will be scored 1, moderate impairment, if they walk with a slower speed, abnormal gait pattern, evidence of imbalance, deviates 10-15 inches outside 12 12-inch walkway width. Participants will be said to have severe impairment, score of 0, if they can not walk 6 meters (20 feet) without assistance, severe gait deviations or imbalance, deviates greater than 15 inches outside 12 12-inch walkway width or will not attempt the task.
Baseline and 4 weeks
Functional mobility - 6-Minute Walk Test (6MWT)
Time Frame: Baseline and 4 weeks
Distance (in meters) covered during a 6-minute walk test to assess aerobic capacity and endurance. Normal score ranges from 400-700 meters. The participants will be asked to walk for 6 minutes, and the distance covered will be noted. The MCID for the 6-minute walk test is 45 meters.
Baseline and 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Khyber Medical University Peshawar

Collaborators

Rehman Medical Institute - RMI

Investigators

  • Principal Investigator: Dr Rida Shabbir, PhD, Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar
  • Principal Investigator: Dr Haider Darain, PhD, Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar
  • Principal Investigator: Dr Aatik Arsh, PhD, Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2025

Primary Completion (Actual)

June 18, 2026

Study Completion (Actual)

June 22, 2026

Study Registration Dates

First Submitted

May 2, 2025

First Submitted That Met QC Criteria

May 2, 2025

First Posted (Actual)

May 11, 2025

Study Record Updates

Last Update Posted (Actual)

June 25, 2026

Last Update Submitted That Met QC Criteria

June 22, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KMU/DIR/CTU/2025/002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

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

IPD Sharing Access Criteria

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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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