Intermittent Hypoxia Paired with High Intensity Training in Brain Injury

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.

Study Overview

• Status: Completed
• Conditions: Brain Injuries
• Intervention / Treatment: Procedure: Intermittent hypoxia; Procedure: Sham hypoxia

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Rehabilitation Hospital of Indiana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• > 6 months post brain injury
• 18-85 years old
• ability to walk without physical assistance
• Self selected walking speed of 0.01-1.0 m/s

Exclusion Criteria:

• <18 years old
• >85 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Intensity Training with Intermittent Hypoxia; 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; 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).
Sham Comparator: High Intensity Training with Sham Hypoxia; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Rehabilitation Hospital of Indiana
• Investigators: Principal Investigator: Thomas Hornby, PT,PhD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms, Respiratory; Brain Injuries; Wounds and Injuries; Hypoxia
• Other Study ID Numbers: IU2001598586

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD available per request

Drug and device information, study documents

• 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.: No