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

NCT05491837 | Recruiting

• 1 other identifier: RIPHAH/RCRS/REC/Letter-0129
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Incomplete Spinal Cord Injury

Outcome Measures

Primary Outcomes (9)

• Upper limb function

  Change in upper limb function will be assessed via 9-Hole peg test (9-HPT) and Box and Block test (BBT).The 9-HPT is used to assess fine movement of hand and finger dexterity. It has excellent reliability and adequate to good concurrent validity with Box and Block test. It should be conducted with the dominant hand first. The participants will be advised to place the pegs into the 9 hole in the board and then again remove each peg and place it in the container. Total time will be measured and it will be compared with the other hand. The BBT is used to test manual dexterity. The participants are requested to move 1 inch block from one box to another in 60 seconds while crossing the partition between the blocks. Total blocks moved will be calculated as test score.

  change will be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• upper limb grip strength

  change in Grip strength will be measured by using hand dynamometer (Model-Jamardigital Hand dynamometer). Participants will be seated with shoulder adducted and neutral rotated, elbow at 90 degree position. The forearm is in between supination and pronation without support of arm rest and the wrist is in neutral position. Maximum contraction will be measured by asking the participants to contract against the hand grip while maintaining the contraction for 3 to 5 seconds. Average of 3 attempts will be calculated as measurement

  change in grip strength will be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• Upper limb Pinch strength

  change in Pinch strength will be measured by using hydraulic gauge. Hydraulic gauge for pinch strength is reliable with ICC 0.821. Pinch strength is used incomplete spinal cord injury tetraplegic populations. The patient is advised to apply force on pinch grove within the device and then gauge will calibrate the total force in pounds or kilograms. All type of pinch strength will be measured and score will be compared with the normal values.

  change in pinch strength will be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• Quick DASH to measure upper limb disability

  Quick Disability of arm, shoulder and Hand (DASH) questionnaire is a self-reporting 11-items questionnaire that measures the ability of patients to perform certain upper limb tasks. The patients can rate their difficulty that they may face during specific upper limb activity on 5 points likert scale. The questionnaire is designed to assess one or more disability of arm shoulder and hand. It has good validity and reliability. The interclass correlation coefficient (ICC) is 0.82 The test retest reliability of the both 11 item and its optional work 15 items are 0.9 and 0.94 respectively and that neither of them are significant difference from that of the original DASH questionnaire

  It will be assed on baseline and after 4 week of interventions

• walking performance

  Change in walking performance will be assessed via 10 meter 'walk test(10MWT). It is used to assess walking performance of individual. It measures times in seconds the participants is taken during 10 meters of walking as quickly as possible using their regular devices. This scale has been validated for iSCI and its test retest, intra-rater are excellent (r= 0.983) while inter-rater r=0.97. The Time up and go test (TUG)is used to evaluate the walking performance of an individual that he takes to stand up from chair and walk 3 meters independently with her/his own pace of walking. Then return to resume his seated position again. Total time in seconds will be calculated. This scale has excellent validity and both test retest and intra rater reliability r=0.98 while inter-rater reliability reported as r=0.97.

  change in walking performance will be measured on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• walking endurance

  Chane in walking endurance will be measured via 6 minute walk test. This scale is validated for patients with iSCI with an excellent inter rater reliability r- 0.98. The participants are advised to walk 6 minutes as far as possible in 6 minutes while total distance in meters is calculated. Participants can rest if needed but they are advised not to sit

  change will be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• lower limb muscle strength

  Lower limb dynamometer is used to quantify strength of lower limb muscles. It assesses isometric strength of lower limb muscles and considered a suitable alternative of conventional manual muscle testing.

  change in lower limb strength be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• balance

  The berg balance scale(BBS) was originally developed for stroke and geriatric population but it's used is also evident in iSCI(40). It is 14-items scale that is used to assess static balance and fall risk in adults. It has been used in various neurological disorders. In incomplete spinal cord injury, it is reported that BBS has excellent inter-observer reliability both for single item and for total items r =.84 and ICC =0.95 (41). The concurrent validated of BBS in regard to spinal cord injury is also reported moderate to high (40). The BBS total score is 56 and less than 45 indicated risk of fall

  change in balance score will be assessed on base line before intervention, post 7 days, post 14 days, post 21 days, post 30 days and a follow up week without intervention for retention effects

• Brain derived Neurotrophic factors (BDNF) to measure plasticity in brain

  Brain derived neurotrophic factors are secreted by the neuron which is one of the important factors in neural plasticity. Effects of various locomotor exercise in incomplete spinal cord injury have been investigated. It is premised that BDNF activate high affinity tropomyosin related kinase receptor subtype B (TrKB) also called tyorosin kinase B that help in rhythmic activity of diagram in cervical incomplete spinal cord injury. In human, BDNFis present in blood platelets where it starts accumulating during synthesis of megakaryocytes. It can be readily detectable in human serum by ELIZA using monoclonal antibodies and thus it is considered reliable and has been largely speculated that it may improve brain functions

  It will be assed on baseline and after 4 week of interventions

Secondary Outcomes (1)

• WHO QOL Urdu version to assess quality of life

  It will be assed on baseline and after 4 week of interventions

Study Arms (2)

Interventional group

EXPERIMENTAL

Interventional group will be provided a brief sequence of acute hypoxia consisting of 9% oxygen via device HYP 123 for one minute followed by normoxia 21% of oxygen for a total of 15 repetition. This protocols will be provided 3 times/week for a period of 4 weeks.

Other: Device induce acute intermittent hypoxia 9 % of Oxygen; Other: Normoxia 21% of oxygen

Control group

SHAM COMPARATOR

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. This protocols will be provided 3 times/week for a period of 4 weeks.

Other: Normoxia 21% of oxygen

Interventions

Device induce acute intermittent hypoxia 9 % of Oxygen OTHER

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

Interventional group

Normoxia 21% of oxygen OTHER

SHAM group will be provided normoxia 21% of Oxygen

Control group; Interventional group

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Riphah International University: lead

Study Sites (1)

Riphah International University Islamabad

Islamabad, 44000, Pakistan

RECRUITING

Related Publications (9)

• Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017 Apr 27;3:17018. doi: 10.1038/nrdp.2017.18.

  PMID: 28447605 BACKGROUND

• Yang R, Guo L, Wang P, Huang L, Tang Y, Wang W, Chen K, Ye J, Lu C, Wu Y, Shen H. Epidemiology of spinal cord injuries and risk factors for complete injuries in Guangdong, China: a retrospective study. PLoS One. 2014 Jan 28;9(1):e84733. doi: 10.1371/journal.pone.0084733. eCollection 2014.

  PMID: 24489652 BACKGROUND

• Navarrete-Opazo A, Alcayaga J, Sepulveda O, Rojas E, Astudillo C. Repetitive Intermittent Hypoxia and Locomotor Training Enhances Walking Function in Incomplete Spinal Cord Injury Subjects: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. J Neurotrauma. 2017 May 1;34(9):1803-1812. doi: 10.1089/neu.2016.4478. Epub 2016 Jul 19.

  PMID: 27329506 BACKGROUND

• Champod AS, Eskes GA, Foster GE, Hanly PJ, Pialoux V, Beaudin AE, Poulin MJ. Effects of acute intermittent hypoxia on working memory in young healthy adults. Am J Respir Crit Care Med. 2013 May 15;187(10):1148-50. doi: 10.1164/rccm.201209-1742LE. No abstract available.

  PMID: 23675727 BACKGROUND

• Manukhina EB, Downey HF, Shi X, Mallet RT. Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease. Exp Biol Med (Maywood). 2016 Jun;241(12):1351-63. doi: 10.1177/1535370216649060. Epub 2016 May 10.

  PMID: 27190276 BACKGROUND

• Viscor G, Torrella JR, Corral L, Ricart A, Javierre C, Pages T, Ventura JL. Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications. Front Physiol. 2018 Jul 9;9:814. doi: 10.3389/fphys.2018.00814. eCollection 2018.

  PMID: 30038574 BACKGROUND

• Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27.

  PMID: 24285617 BACKGROUND

• Sandhu MS, Perez MA, Oudega M, Mitchell GS, Rymer WZ. Efficacy and time course of acute intermittent hypoxia effects in the upper extremities of people with cervical spinal cord injury. Exp Neurol. 2021 Aug;342:113722. doi: 10.1016/j.expneurol.2021.113722. Epub 2021 Apr 28.

  PMID: 33932397 BACKGROUND

• Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012 Feb;26(2):163-72. doi: 10.1177/1545968311412055. Epub 2011 Aug 5.

  PMID: 21821826 BACKGROUND

MeSH Terms

Interventions

Oxygen

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Study Officials

• Ikram Ali, Master

  Riphah International University Islamabad

  PRINCIPAL INVESTIGATOR

• Waqar Ahmed Awan, PhD

  Riphah International University Islamabad

  STUDY CHAIR

Central Study Contacts

Ikram Ali, Master

CONTACT

00923343475727; drikramali@gmail.com

Waqar Ahmed, PhD

CONTACT

00923335348846; waqar.ahmed@riphah.edu.pk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients 'selection and their allocation of treatments to experimental and control will be done by team of physiotherapists working in paraplegic center Peshawar who 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. The investigator, patients and the treatment providers will be anonymous from the group allocation, treatment they receive and data analysis
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The participants are randomly divided into 2 groups. Interventional and SHAM

Study Record Dates

• First Submitted: July 24, 2022
• First Posted: August 8, 2022
• Study Start: January 1, 2023
• Primary Completion: October 30, 2024
• Study Completion: November 4, 2024
• Last Updated: September 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)