Intermittent Hypoxia Paired With High Intensity Training in Brain Injury

Study Overview
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Brief Summary
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The central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains as compared to HIT alone; 2) improvements in gait quality and motor coordination during walking, and 3) changes in measures of community participation and integration.

Detailed Description
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The central hypotheses are that HIT combined with AIH results in: 1) greater locomotor gains as compared to HIT alone; 2) improvements in gait quality and motor coordination during walking, and 3) changes in measures of community participation and integration. To test these hypotheses, the proposed crossover, assessor-blinded, randomized clinical trial (RCT) is designed to test the effects of safety, feasibility, and preliminary efficacy of HIT+AIH. In this phase I-II trial, patients >6 months post-BI with mobility deficits will be allocated to 5 weeks (15 sessions) of HIT+AIH or HIT alone. Blinded assessments will be performed prior to and following training paradigms to address 3 specific aims.

Official Title
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Intermittent Hypoxia Paired With High Intensity Training in Brain Injury

Conditions
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Brain Injuries

Intervention / Treatment
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* Procedure: Intermittent hypoxia
* Procedure: Sham hypoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 6 months post brain injury 18-75 years old ability to walk without physical assistance Self selected walking speed of 0.01-1.0 m/s Exclusion Criteria: <18 years old ->75 years old self selected walking speed of > 1.0 m/s < 3 months from botulinum toxin injection above the knee brace Currently receiving physical therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2-arm, randomized, crossover trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Intensity Training with Intermittent Hypoxia<br>The primary goal will be provide acute intermittent hypoxia (9% PO2; 1 min on 1 min off) prior to stepping training while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). Sessions will be divided into  10 minute increments ( 25% of sessions) between speed-dependent treadmill training (described above for treadmill stepping), skill-dependent treadmill training, overground training, and stair climbing. | Procedure: Intermittent hypoxia<br>* Acute intermittent treatment (AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. AIH (using 9% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented. High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).<br>|
| Sham Comparator: High Intensity Training with Sham Hypoxia<br>The primary goal will be provide sham intermittent hypoxia (20% PO2) prior to performing continuous stepping while maintaining HR within 70-85% maximum predicted HR (if patients are deconditioned, PTs will gradually increase intensity to desired levels as tolerated). Sessions will be divided into  10 minute increments ( 25% of sessions) between speed-dependent treadmill training (described above for treadmill stepping), skill-dependent treadmill training, overground training, and stair climbing. | Procedure: Sham hypoxia<br>* Sham acute intermittent treatment (sham AIH) will be initiated using an oxygen generator (Model HYP-123, Hypoxico Inc, New York, NY, and participants will be seated comfortably and fitted with a non-rebreather mask. Sham AIH (using 20% O2) will be provided in 60 s intervals and repeated 15 times with alternating 60 s intervals of normoxia (21% O2). Continuous pulse oximetry (Masimo 7, Irvine CA) will be monitored to ensure oxygen saturation of 82-85%. Signs and symptoms of distress with AIH exposure will be noted throughout, with HR and blood pressure taken every 3-5 minutes and documented. High-intensity training will then be performed (40 min of walking training up to 70-80% maximum heart rate within 1 hr).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gait speed | Gait speed is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait speed will be measured at self-selected speeds (SSS; instructions to walk at normal comfortable pace) and fastest-possible speed (FS: as fast as you safely can) using the Zeno Walkway (Protokinetics, Haverton, PA). | Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 6 weeks | 
| Change in Endurance | Endurance is valid, reliable, and sensitive measures related to overall functional ability, and will be assessed by blinded rates. This measure will be performed by blinded assessors who do not participate in the training. Gait endurance will be tested using the 6MWT (m) with instructions similar to SSS to minimize fall risk. | Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic capacity | Peak metabolic capacity will be observed during graded exercise testing on a treadmill wtih peak oxygen consumption | Baseline 1, Post 1 after 6 weeks, Baseline 2, Post 2 after 6 weeks |