Intermittent Hypoxia-Hyperoxia Combined With Physical Therapy for Knee Osteoarthritis

NCT06965946 | Recruiting DMC

• 1 other identifier: KMU/DIR/CTU/2025/002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Osteo Arthritis Knee

Keywords

Knee Osteoarthritis; Intermittent Hypoxia; Hypoxic-Hyperoxic Therapy; Rehabilitation; Functional Mobility

Outcome Measures

Primary Outcomes (4)

• Pain Reduction

  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

  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)

  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 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 Outcomes (2)

• Gait Performance - Functional Gait Assessment (FGA) Score

  Baseline and 4 weeks

• Functional mobility - 6-Minute Walk Test (6MWT)

  Baseline and 4 weeks

Study Arms (2)

Intermittent Hypoxia-Hyperoxia + Conventional Therapy

EXPERIMENTAL

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); Procedure: Conventional Physical Therapy

Conventional Therapy with Normoxic Air

ACTIVE COMPARATOR

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; Procedure: Normoxic Air Placebo

Interventions

Intermittent Hypoxia-Hyperoxia Therapy (IHHT) PROCEDURE

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.

Also known as: Olive OLV 10H Hypoxia Generator

Intermittent Hypoxia-Hyperoxia + Conventional Therapy

Conventional Physical Therapy PROCEDURE

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.

Conventional Therapy with Normoxic Air; Intermittent Hypoxia-Hyperoxia + Conventional Therapy

Normoxic Air Placebo PROCEDURE

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.

Conventional Therapy with Normoxic Air

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead
• Rehman Medical Institute - RMI: collaborator

Study Sites (1)

Rehman Medical Institute

Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan

RECRUITING

Related Publications (7)

• Mohd Yunus MH, Lee Y, Nordin A, Chua KH, Bt Hj Idrus R. Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions. Int J Mol Sci. 2022 May 11;23(10):5356. doi: 10.3390/ijms23105356.

  PMID: 35628163 BACKGROUND

• Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26;29-30:100587. doi: 10.1016/j.eclinm.2020.100587. eCollection 2020 Dec.

  PMID: 34505846 BACKGROUND

• Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021 Feb 9;325(6):568-578. doi: 10.1001/jama.2020.22171.

  PMID: 33560326 BACKGROUND

• Rahimi F, Sadeghisani M, Karimzadeh A. Efficacy of transcranial direct current stimulation in patients with knee osteoarthritis: A systematic review. Neurophysiol Clin. 2023 Dec;53(6):102918. doi: 10.1016/j.neucli.2023.102918. Epub 2023 Nov 8.

  PMID: 37944293 BACKGROUND

• Benderdour M, Martel-Pelletier J, Pelletier JP, Kapoor M, Zunzunegui MV, Fahmi H. Cellular Aging, Senescence and Autophagy Processes in Osteoarthritis. Curr Aging Sci. 2015;8(2):147-57. doi: 10.2174/1874609808666150727111530.

  PMID: 26212056 BACKGROUND

• Chang WJ, Bennell KL, Hodges PW, Hinman RS, Young CL, Buscemi V, Liston MB, Schabrun SM. Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial. PLoS One. 2017 Jun 30;12(6):e0180328. doi: 10.1371/journal.pone.0180328. eCollection 2017.

  PMID: 28665989 BACKGROUND

• Azizi S, Rezasoltani Z, Najafi S, Mohebi B, Tabatabaee SM, Dadarkhah A. Transcranial direct current stimulation for knee osteoarthritis: a single-blind randomized sham-controlled trial. Neurophysiol Clin. 2021 Aug;51(4):329-338. doi: 10.1016/j.neucli.2020.12.002. Epub 2020 Dec 13.

  PMID: 33323306 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Rida Shabbir, PhD*

CONTACT

+923460113227; ridashabbir@kmu.edu.pk

Dr Haider Darain, PhD

CONTACT

+923419990915; haiderdarain@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two-arm parallel-group randomized controlled trial. Participants will be randomly assigned to either the experimental group receiving intermittent hypoxia-hyperoxia therapy along with conventional physical therapy or to the control group receiving conventional physical therapy with normoxic air. Both groups will receive 12 treatment sessions over four weeks.

Study Record Dates

• First Submitted: May 2, 2025
• First Posted: May 11, 2025
• Study Start: May 15, 2025
• Primary Completion: October 31, 2025
• Study Completion: November 30, 2025
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be made available beginning 6 months after publication of the trial results and will remain available for 5 years.
• 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.

Locations

PA (1)