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

NCT06906536 | Enrolling By Invitation

• 2 other identifiers: 23-12751R03HD115657-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

INCOMPLETE SPINAL CORD INJURY (ASIA D); Able Bodied

Keywords

Acute Intermittent Hypoxia; Spinal cord injury; Force steadiness

Outcome Measures

Primary Outcomes (7)

• 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 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 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 Outcomes (3)

• Axial damage ratio

  Baseline

• 6-Minute Walk Test

  Baseline and Day 4

• 10-Meter Walk Test

  Baseline and Day 4

Study Arms (2)

AIH Group

EXPERIMENTAL

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)

SHAM Group

NO INTERVENTION

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.

Interventions

Acute Intermittent Hypoxia (AIH) OTHER

4 consecutive days of 15, 1.5 min episodes at 9% O2 (AIH) alternating with 21% O2 at 1 min intervals

AIH Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Andrew Tan

Boulder, Colorado, 80309, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: April 2, 2025
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-03

Locations

US (1)