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Effects of Intermittent Hypoxia in Upper and Lower Limb Functions in Persons With Incomplete Spinal Cord Injury

Effects of Intermittent Hypoxia in Upper and Lower Limb Functions in Persons With Incomplete Spinal Cord Injury

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18 years and older
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Overview

Spinal cord injury (SCI) is a devastating disability with physical, social and vocational consequences. Owing to its overwhelming complications, the cost of treatment and rehabilitation increases constantly. Persons with spinal cord injury are always dependent on their families in most of house hold, recreational and activities of daily life. Majority of SCI are incomplete classification C or D as per American spinal injury Association (ASIA). Due to certain spared pathways intrinsic mechanism of neuroplasticity take place in incomplete spinal cord injuries (iSCI) which is liable for natural recovery, but this potential is limited and often slow. Therefore there is need for some advance therapeutic interventions which may enhance neuroplasticity and improve functional recovery in individuals with iSCI.

It has been reported that acute intermittent hypoxia (AIH) increase neuro plasticity by causing release of spinal serotonin which stimulate serotonin type 2 (5-HT2) receptors that undergoes a series of mechanisms which increase brain derived neurotrophic factors (BDNF) which subsequently enhance motor functions of upper and lower limbs in iSCI.

Despite of the growing body of literatures supporting that AIH improves both upper limb and lower limb functions along with walking ability and speed. However, their results are limited to small sample size, gender biased and lack of intralimbs assessment. As per the author knowledge, these literatures lack retention effects of AIH on upper and lower limb function. In addition variables like quality of life, disability and some biomarkers related to hypoxic effects have not been reported in any of these studies. Furthermore, it is hypothesized that variant geographic locations and socioeconomic status may affects persons with iSCI differently. So in light of these literature gaps, the author aim is to investigate the effects of AIH in upper and lower limb motor function, balance, quality of life and disability. In addition, the effects of AIH on brain derived neurotrophic factors (BDNF), hemoglobin (Hb) level, numbers of RBS and hematocrits will be assessed.

Description

Study design and setting: This will be Randomized Controlled Trail triple blind study design. The study will be conducted in Paraplegic center Peshawar (PCP) Pakistan https://paraplegiccenter.org/.

Blinding of the participants: Patients 'selection and their allocation of treatments to experimental and control will be done by team of physiotherapists working in paraplegic center Peshawar whose will not the part of investigation team. Treatment will be given by trained physiotherapist within paraplegic center Peshawar while data will be analyzed by statistician working in Riphah international University Islamabad Pakistan. The investigators, patients and the treatment providers will be anonymous from the group allocation, treatment they receive and data analysis.

Sampling Technique: Since the sample frame is available so sample technique will be Random Sampling by computer generated table of random number.

Sample size: Sample size for the study calculated via G Power sample size calculator with power of 95% and α error probability is 0.05 on the following assumption.

Walking speed (10MWT) post intervention in groups are: IH= 17.1±5.8 vs. Nx=7.1±2.8s. the effect was determined as 2.09. So the total sample size for both groups is 8 (4). Since this sample size is less so we consider our effect size 0.9 thus total sample size will be 68, each grip will be having 34 participants.

Participants: Person with incomplete spinal cord injury will be our study participants.

Tools/Outcome measures include the following

  1. Hypoxico Hyp 123
  2. Hand Dynamometer (Grip strength) Hydraulic guage (pinch strength)
  3. Upper limb functional Test (9-Hole and Pegs Test, Box and Block Test)
  4. Quick-DASH (Disability of arm, shoulder and hand)
  5. Ten Minute Walk Test ,Time up and Go Test (walking performance)
  6. Six Minute Walk Test(endurance)
  7. Berg Balance Test (Balance)
  8. WHO-QOL (BREF Urdu version)
  9. Brain derived neurotrophic factors (BDNF)
  10. Level of Hemoglobin, RBS and Hematocrits Interventions details: After randomly allocation of the patients into intervention and SHAM group. The Interventional group will be provided a brief sequence of mild hypoxia consisting of 9% oxygen for one minute followed by normoxia 21% of oxygen for a total of 15 episodes. The SHAM group' participants will be provided 21% of O2 (normoxia), comprised of 15 repetitions of 1-minute then switching to another 1-minute of 21% O2. Both these protocols will be provided 3 times/week for a period of 4 weeks. Both groups will continue their routine rehabilitation for the upper and lower limb exerccises within the center. Post assessments for the said variable will be carried out each week (post 7 days, post 14 days, post 21 days, post 30 days and a follow up week for retention effects).

Data collection Procedure: After informed consent, all the willing and eligible participants will be randomly divided into intervention and SHAM group. Participant's demographic details will be taken which includes participant's age, geographic location, socioeconomic status, history of onset of iSCI, level of spinal cord injury, ASIA classification C/D and BMI. Outcome measure will be assessed as baseline at each week and after final as retention effect ass discussed above.

Ethical consideration: Ethical consideration has been provided by the ethical board of Riphah International University Islamabad RIPHAH/RCRS/REC/Letter-0129 dated march 2022.

Eligibility

Inclusion Criteria:

  1. Incomplete SCI≥ 3 months(21);
  2. Traumatic and non-traumatic, non-progressive lesions, Aged ≥ 18 years ;
  3. LesionC4 and below as classified ASIA category C and D;
  4. Both gender
  5. Ability to ambulate with or without assistive devices; and
  6. Ability to follow verbal and visual command.

Exclusion Criteria:

  1. Participants with complete spinal cord injury;
  2. Unstable orthopedic injuries and joint contractures
  3. Osteoporosis with high risk of fracture;
  4. Pressure ulcers and cutaneous lesion(4)
  5. Cognitive impairment, severe cardiopulmonary complication such as severe breathing disorder

Study details
    Incomplete Spinal Cord Injury

NCT05491837

Riphah International University

21 October 2025

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