Effects of Caffeine and Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury

Mass General Brigham

Status and phase: Completed; Phase 2; Phase 1

Conditions: Spinal Cord Injuries

Treatments: Other: SHAM; Other: AIH; Other: Placebo; Drug: Caffeine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02323698

5R01HD081274 (U.S. NIH Grant/Contract)

2017P001940b

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• age 18 and 75 years (the latter to reduce likelihood of heart disease)
• medical clearance to participate
• lesion at or below C2 and above L5 with non-progressive etiology
• classified as motor-incomplete with visible volitional leg movement
• injury greater than 6 months
• ability to advance one step overground without human assistance

Exclusion criteria

• Concurrent severe medical illness (i.e., infection, cardiovascular disease, ossification, recurrent autonomic dysreflexia, unhealed decubiti, and history of pulmonary complications)
• Pregnant women because of the unknown affects of AIH on pregnant women and fetus
• History of seizures, brain injury, and/or epilepsy
• Undergoing concurrent physical therapy
• Diabetes
• Cirrhosis
• Caffeine and/or NSAID allergies or intolerances

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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36 participants in 3 patient groups

Caffeine/AIH

Active Comparator group

Description:

Subjects with chronic, motor-incomplete SCI receive Caffeine then AIH

Treatment:

Drug: Caffeine

Other: AIH

Placebo/AIH

Active Comparator group

Description:

Subjects with chronic, motor-incomplete SCI receive Placebo then AIH

Treatment:

Other: Placebo

Other: AIH

Caffeine/SHAM

Active Comparator group

Description:

Subjects with chronic, motor-incomplete SCI receive Caffeine then SHAM

Treatment:

Drug: Caffeine

Other: SHAM