Intermittent Hypoxia-Hyperoxia Combined With Physical Therapy for Knee Osteoarthritis

NCT ID: NCT06965946

Last Updated: 2025-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-15

Study Completion Date

2025-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Osteo Arthritis Knee

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

Intermittent Hypoxia-Hyperoxia Therapy (IHHT)

Intervention Type 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.

Conventional Physical Therapy

Intervention Type 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

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).

Group Type ACTIVE_COMPARATOR

Conventional Physical Therapy

Intervention Type 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.

Normoxic Air Placebo

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type PROCEDURE

Other Intervention Names

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Olive OLV 10H Hypoxia Generator

Eligibility Criteria

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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.
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rehman Medical Institute - RMI

OTHER

Sponsor Role collaborator

Khyber Medical University Peshawar

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr Rida Shabbir, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar

Dr Haider Darain, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar

Dr Aatik Arsh, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar

Locations

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Rehman Medical Institute

Peshawar, Khyber Pakhtunkhwa, Pakistan

Site Status RECRUITING

Countries

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Pakistan

Central Contacts

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Dr Rida Shabbir, PhD*

Role: CONTACT

+923460113227

Dr Haider Darain, PhD

Role: CONTACT

+923419990915

Facility Contacts

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Dr Rida Shabbir, PhD

Role: primary

+923460113227

Dr Muhammad Bin Afsar Jan, MS

Role: backup

+923339118440

References

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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.

Reference Type BACKGROUND
PMID: 35628163 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34505846 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33560326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37944293 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26212056 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28665989 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33323306 (View on PubMed)

Other Identifiers

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KMU/DIR/CTU/2025/002

Identifier Type: -

Identifier Source: org_study_id

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