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Trial record 1 of 1 for:    NCT02323945
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Effects of Breathing Mild Bouts of Low Oxygen on Limb Mobility After Spinal Injury

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ClinicalTrials.gov Identifier: NCT02323945
Recruitment Status : Recruiting
First Posted : December 24, 2014
Last Update Posted : December 4, 2017
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Foundation Wings For Life
Information provided by (Responsible Party):
Randy Trumbower, PT, PhD, Harvard Medical School

Brief Summary:
Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods (termed intermittent hypoxia) is a safe and effective treatment strategy to promote meaningful functional recovery in persons with chronic spinal cord injury (SCI). The goal of the study is to understand the mechanisms by which intermittent hypoxia enhances motor function and spinal plasticity (ability of the nervous system to strengthen neural pathways based on new experiences) following SCI.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Other: AIH Other: Walk Other: Strength Phase 1 Phase 2

Detailed Description:

Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods (termed intermittent hypoxia) is a safe and effective treatment strategy to promote meaningful functional recovery in persons with chronic spinal cord injury. Repetitive exposure to mild hypoxia triggers a cascade of events in the spinal cord, including new protein synthesis and increased sensitivity in the circuitry necessary for breathing and walking. Recently, the investigators demonstrated that daily (5 consecutive days) of intermittent hypoxia stimulated walking enhancement in persons with chronic spinal cord injury.

Despite these exciting findings, important questions remain. First, does intermittent hypoxia improve walking recovery by increasing strength or muscle coordination or both? Understanding its mechanisms will allow us to best apply intermittent hypoxia in the clinic. Second, initial studies indicate that the beneficial effects of intermittent hypoxia are greatest when intermittent hypoxia is used just prior to task training and that the benefits are greatest for the practiced task. The investigators will explore this possibility by examining the effects of intermittent hypoxia on walking ability and force production when applied alone and when applied in combination with walking training or strength training. The investigators expect that the greatest improvements in walking ability for intermittent hypoxia with walking training and the greatest improvements in strength in response to intermittent hypoxia with strength training. Third, studies suggest that intermittent hypoxia induces spinal plasticity by increasing the expression of a key plasticity-promoting protein, brain-derived neurotrophic factor (BDNF). Mutations in the BDNF gene have been shown to impair BDNF functionality. Thus, the investigators will also explore the impact of BDNF polymorphisms on responsiveness to intermittent hypoxia therapy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mechanisms of Intermittent Hypoxia-induced Motor Recovery in Persons With SCI
Study Start Date : October 2014
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: AIH/Walk
Subjects with chronic, motor-incomplete SCI receive acute intermittent hypoxia (AIH) with walking practice, then AIH with strength practice and compare their efficacy on enhancing strength and/or walking performance.
Other: AIH
Participants will breath intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FiO2) = 0.09±0.02 (hypoxia). Participants will receive treatment on 5 consecutive days.
Other Name: Acute Intermittent Hypoxia

Other: Walk
30 minutes of walking practice consisting of 5 repetitions of 6-minute walks

Active Comparator: AIH/Strength
Subjects with chronic, motor-incomplete SCI receive AIH with strength practice, then AIH with walking practice and compare their efficacy on enhancing strength and/or walking performance.
Other: AIH
Participants will breath intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of fraction of inspired oxygen (FiO2) = 0.09±0.02 (hypoxia). Participants will receive treatment on 5 consecutive days.
Other Name: Acute Intermittent Hypoxia

Other: Strength
30 minutes of isometric ankle plantar flexion torque practice broken into 3 sets of 10 repetitions




Primary Outcome Measures :
  1. Change in overground walking endurance [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Endurance will be measured as the distance walked during 2 min and 6 min (6MWT).

  2. Change in muscle strength [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Strength will be assessed as the maximum isometric torque produced by the ankle and measured by a 6 degrees-of-freedom (DOF) load cell.


Secondary Outcome Measures :
  1. Change in overground walking speed [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Speed will be assessed by the time required to walk 10 meters (10MWT).



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18 and 75 years (the latter to reduce likelihood of heart disease)
  • Medical clearance to participate
  • Lesion at or below C2 and above T12 with non-progressive etiology
  • Classified as motor-incomplete with visible volitional leg movement
  • Injury greater than 1 year

Exclusion Criteria:

  • Concurrent severe medical illness (i.e., infection, cardiovascular disease, ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of pulmonary complications)
  • Pregnant women because of the unknown affects of AIH on pregnant women and fetus
  • History of seizures, brain injury, and/or epilepsy
  • Undergoing concurrent physical therapy
  • Diabetes
  • Cirrhosis
  • Caffeine and/or NSAID allergies or intolerances

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02323945


Contacts
Contact: Randy D Trumbower, PT, PhD 617-952-6951 randy.trumbower@mgh.harvard.edu
Contact: Lorna Brown, DPT 617-952-6831 labtrumbower@gmail.com

Locations
United States, Massachusetts
Spaulding Rehabilitation Hospital Recruiting
Cambridge, Massachusetts, United States, 02138
Contact: Randy D Trumbower, PT, PhD    617-952-6951    randy.trumbower@mgh.harvard.edu   
Contact: Lorna Brown, DPT    (617) 952-6950    labtrumbower@gmail.com   
Sponsors and Collaborators
Spaulding Rehabilitation Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Foundation Wings For Life
Investigators
Principal Investigator: Randy D Trumbower, PT, PhD Harvard Medical School

Publications:
Responsible Party: Randy Trumbower, PT, PhD, Assistant Professor, Harvard Medical School
ClinicalTrials.gov Identifier: NCT02323945     History of Changes
Other Study ID Numbers: 2017P001940a
1R01HD081274-01 ( U.S. NIH Grant/Contract )
First Posted: December 24, 2014    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Randy Trumbower, PT, PhD, Harvard Medical School:
acute intermittent hypoxia
incomplete spinal cord injury
strength
walking
breathing

Additional relevant MeSH terms:
Wounds and Injuries
Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System