Clinical trial NCT06965946: Intermittent Hypoxia-Hyperoxia Combined With Physical Therapy for Knee Osteoarthritis
Official title: Effectiveness of Combining Intermittent Hypoxia-Hyperoxia and Conventional Physical Therapy for Patients With Knee Osteoarthritis: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Osteo Arthritis Knee
Keywords: Knee Osteoarthritis
Intermittent Hypoxia
Hypoxic-Hyperoxic Therapy
Rehabilitation
Functional Mobility
Lead sponsor: Khyber Medical University Peshawar
Sponsor class: OTHER
Collaborators: name: Rehman Medical Institute - RMI
First posted: 2025-05-11
Enrollment: 60
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pain Reduction
timeFrame: Baseline and after 4 weeks (12 sessions of therapy)
measure: Functional Status - KOOS Activities of Daily Living Subscale
timeFrame: Baseline and after 4 weeks
measure: Inflammatory Marker - C-Reactive Protein (CRP)
timeFrame: Baseline and after 4 weeks
measure: Balance - Timed Up and Go Test (TUG)
timeFrame: Baseline and after 4 weeks
Secondary outcomes:
measure: Gait Performance - Functional Gait Assessment (FGA) Score
timeFrame: Baseline and after 4 weeks
measure: Functional mobility - 6-Minute Walk Test (6MWT)
timeFrame: Baseline and after 4 weeks
Other outcomes:
Locations:
city: Peshawar
country: Pakistan
facility: Rehman Medical Institute
state: Khyber Pakhtunkhwa
Study officials:
affiliation: Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar
name: Dr Rida Shabbir, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar
name: Dr Haider Darain, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Physical Medicine and Rehabilitation, Khyber Medical University Peshawar
name: Dr Aatik Arsh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.