Examining the Effect of Acute Intermittent Hypoxia on Serum Blood Proteins and Lower Limb Function

Examining the Effect of Acute Intermittent Hypoxia on Serum Blood Proteins, Corticospinal Excitability, and Force Control in Persons With Incomplete Spinal Cord Injury

The goal of this study is to clarify mechanisms of acute intermittent hypoxia and to examine the effect on lower limb function in persons with chronic, incomplete spinal cord injury.

Study Overview

• Status: Enrolling by invitation
• Conditions: INCOMPLETE SPINAL CORD INJURY (ASIA D); Able Bodied
• Intervention / Treatment: Other: Acute Intermittent Hypoxia (AIH)

Detailed Description

The goal of this study is to clarify mechanisms of acute intermittent hypoxia by examining changes in blood biomarkers, neural excitability, and hemoglobin mass. We also aim to clarify how these changes relate to changes in lower limb function in persons with chronic, incomplete spinal cord injury by measuring force steadiness and voluntary muscle activation.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • Andrew Tan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 to 75 years old (the latter to reduce likelihood of heart disease)
• Medically stable with medical clearance from physician to participate
• Motor-incomplete spinal cord injuries at or below C2 and at or above L5
• AIS A-D at initial screen, or other non-traumatic spinal cord injury disorders (e.g. multiple sclerosis, ALS, tumors, acute transverse myelitis, etc.)
• More than 1 year since iSCI to minimize confounds of spontaneous neurological recovery
• Ability to advance one step overground with or without assistive devices;

Exclusion Criteria:

• Severe concurrent illness or pain
• Recurrent autonomic dysreflexia
• History of cardiovascular/pulmonary complications
• Concurrent physical therapy
• Pregnant at time of enrollment or planning to become pregnant
• Untreated painful musculoskeletal dysfunction, fracture or pressure sore
• History of seizures or epilepsy
• Recurring headaches
• Concussion within the last six months
• Depression or manic disorder
• Metal implants in the head, or pacemaker
• Aversion to needles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIH Group; Participants will be exposed to 4 consecutive days of acute intermittent hypoxia (AIH): 15, 1.5 min episodes at 9% O2 alternating with 21% O2 at 1 min intervals.	Other: Acute Intermittent Hypoxia (AIH); 4 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals
No Intervention: SHAM Group; Participants will be exposed to 4 consecutive days of normoxia: 15, 1.5 min episodes at 21% O2 alternating with 21% O2 at 1 min intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Transcranial Magnetic Stimulation Recruitment Curve Slope	The mean motor evoked potential response will be plotted against the corresponding stimulation intensity (% resting motor threshold) to produce a stimulus-response curve at 20% and 40% of maximum. We will measure TMS before the start of 4 consecutive days of AIH exposure. We will measure TMS within 24 hours of the final AIH exposure.	Baseline and Day 4
Change in Force Steadiness	The coefficient of variation of force will be calculated in both plantarflexion and dorsiflexion at 20% and 40% of maximum. We will measure coefficient of variation of force before the start of 4 consecutive days of AIH exposure. We will measure coefficient of variation of force within 24 hours of the final AIH exposure.	Baseline and Day 4
Change in Central Activation Ratio	We will measure the central activation ratio using supramaximal electrical stimulus over a peripheral nerve during maximum voluntary activation. We will measure the central activation ratio before the start of 4 consecutive days of AIH exposure. We will measure the central activation ratio within 24 hours of the final AIH exposure.	Baseline and Day 4
Change in hemoglobin mass	Using the optimized carbon monoxide rebreathing procedure we will evaluate hemoglobin concentration, carboxyhemoglobin, and hematocrit to calculate total hemoglobin mass, blood volume, and plasma volume. The optimized carbon monoxide rebreathing procedure will be done prior to the first hypoxia exposure and following the 4th hypoxia exposure.	Baseline and Day 4
Change in Serum Blood Brain Derived Neurotrophic Factor	Serum blood brain derived neurotrophic factor (pg/mL) will be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.	Baseline, Day 1, Day 3, and Day 4
Change in Serum Serotonin	Serum serotonin (ng/mL) be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.	Baseline, Day 1, Day 3, and Day 4
Change in Serum Erythropoetin	Serum erythropoetin (mU/mL) will be assessed using enzyme-linked immunosorbent assay. Blood will be sampled prior to AIH and within 1 hour following the 1st, 3rd, and 4th AIH exposure.	Baseline, Day 1, Day 3, and Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Axial damage ratio	Using MRI, we will quantify the axial damage ratio. Prior to participation in the study we will obtain an MRI for quantification of axial damage ratio	Baseline
6-Minute Walk Test	We will assess the distance walked in 6-minutes. The 6-minute walk test will be completed prior to the first exposure to hypoxia and following the 4th exposure of hypoxia.	Baseline and Day 4
10-Meter Walk Test	We will assess how long it takes subjects to walk 10 meters. The 10-Meter walk test will be done prior to the first hypoxia exposure, and following the 4th hypoxia exposure.	Baseline and Day 4

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: University of Colorado, Denver; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Spinal cord injury; Acute Intermittent Hypoxia; Force steadiness
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Signs and Symptoms, Respiratory; Trauma, Nervous System; Spinal Cord Diseases; Hypoxia; Spinal Cord Injuries
• Other Study ID Numbers: 23-1275; 1R03HD115657-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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