Non-Invasive Interventions for Respiratory Recovery in Chronic Spinal Cord Injury

Description

The overall objectives of this study are:

To determine whether combining hypercapnic-hypoxia protocol (HiCO₂-AIH) and transcutaneous spinal cord stimulation (tSCS) can enhance the effects of respiratory resistance training in individuals with chronic spinal cord injury (SCI).

To explore whether genetic and blood-based biomarkers can help predict how individuals respond to this combined intervention.

We will test these objectives in adults with chronic SCI using a Williams cross-over design. The study will include 16 participants (with statistical power >0.8 and α=0.05), accounting for a 20% dropout rate, for a total enrollment of 20 participants.

Specific Aims

Aim 1:

To determine whether four consecutive days of combined HiCO₂-AIH and tSCS will improve the effectiveness of respiratory resistance training compared to either intervention alone.

Outcomes (measured from PRE to 1 day POST intervention):

Primary Outcome: Change in mouth occlusion pressure at 0.1 seconds (P0.1). Secondary Outcomes: Maximal inspiratory and expiratory pressure generation, forced vital capacity (FVC), neurophysiological measures of cortico-spinal drive (amplitude of transcranial magnetic stimulation [TMS]) and local spinal excitability (amplitude of cervical magnetic stimulation [CMS]) in the diaphragm.

Safety Outcomes: Continuous monitoring of respiratory parameters (end tidal oxygen [O₂] and carbon dioxide [CO₂] concentration, oxygen saturation [SpO₂]) and cardiovascular parameters (blood pressure [BP], heart rate [HR], and electrocardiogram [ECG]) during each session.

Aim 2:

To identify predictive factors for treatment response to the combined HiCO₂-AIH and tSCS intervention using:

1. Genetic polymorphisms related to intermittent hypoxia signaling pathways.
2. Molecular markers of neurotrauma and inflammation found in blood extracellular vesicles (EVs).

Outcomes:

Regression analyses will be conducted to examine the relationship between treatment outcomes and:

Specific genetic single nucleotide polymorphisms (SNPs). Blood-based molecular markers of neurotrauma and inflammation.