Effects of Caffeine and Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries; Hypoxia; Wounds and Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Accumulating evidence suggests that repeatedly breathing low oxygen levels for brief periods
      (termed intermittent hypoxia) is a safe and effective treatment strategy to promote
      meaningful functional recovery in persons with chronic spinal cord injury (SCI). The goal of
      the study is to understand how caffeine may augment the effects of intermittent hypoxia on
      motor function and spinal plasticity (ability of the nervous system to strengthen neural
      pathways based on new experiences) following SCI.
    

Detailed description: 
      The investigators will examine the effects of acute intermittent hypoxia (AIH) as a possible
      therapeutic intervention to promote functionally useful motor recovery. In this sub-study,
      the investigators will assess changes in leg motor function in response to repetitive AIH
      with and without caffeine.

      Participants will receive caffeine+AIH, placebo+AIH, caffeine+SHAM in a randomized order.
      Before each intervention round, subjects will be asked to avoid caffeine-containing
      substances for 48 hrs (> 5* half-life of ~7 hrs) prior to arrival to control for baseline
      plasma levels of caffeine. Subjects will then ingest capsules containing either placebo
      (dextrose) or caffeine (up to 6mg/kg). Capsules will be prepared by Johnson Compounding &
      Wellness. Blood samples will be collected before and after the breathing intervention to
      assess caffeine concentrations within the body.

      During and after each intervention, both the rate and extent of magnitude changes in
      voluntary and involuntary muscle response behaviors important for walking will be compared
      between interventions within participants. Repeated measurements will be collected on all
      subjects that participate in the multiple interventions.
    

Intervention name(s): Caffeine; AIH; Placebo; SHAM
Intervention type(s): Drug; Other; Other; Other
Intervention description(s): Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 30min after consumption to approximately coincide with peak plasma concentrations.Throughout the 30min wait time and experimentation, blood pressure and heart rate will be monitored.; Participants will breathe intermittent low oxygen via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.10±0.02 (hypoxia). Throughout experimentation, blood pressure and heart rate will be monitored.; This is a placebo counterpart to the caffeine drug. Subjects will ingest capsules containing dextrose. Experiments will begin 30min after consumption to mimic the caffeine drug protocol. Throughout experimentation, blood oxygenation, blood pressure and heart rate will be monitored.; This is a placebo counterpart to breathing intermittent low oxygen. Participants will breathe intermittent room air via air generators. The generators will fill reservoir bags attached to a non-rebreathing face mask. Oxygen concentration will be continuously monitored to ensure delivery of FIO2 (fraction of inspired oxygen) = 0.21±0.02 (normoxia). Throughout experimentation, blood pressure and heart rate will be monitored.
Other intervention name(s): caffeine anhydrous; Acute intermittent hypoxia
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Balanced design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: hypoxia; spinal cord injury; rehabilitation; strength; walk; function; low oxygen