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Effects of Caffeine and Low Oxygen Therapy on Leg Function in Human Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT02323698
Recruitment Status : Recruiting
First Posted : December 23, 2014
Last Update Posted : December 4, 2017
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Foundation Wings For Life
Information provided by (Responsible Party):
Randy Trumbower, PT, PhD, Harvard Medical School

December 18, 2014
December 23, 2014
December 4, 2017
October 2014
May 2020   (Final data collection date for primary outcome measure)
Change in overground walking speed [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
Speed will be assessed by the time required to walk 10 meters (10MWT).
  • Change in overground walking speed [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Speed will be assessed by the time required to walk 10 meters (10MWT).
  • Change in muscle strength [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Ankle strength will be assessed by the maximum isometric plantar flexion torque produced by the ankle and measured by a 6-DOF load cell.
Complete list of historical versions of study NCT02323698 on ClinicalTrials.gov Archive Site
Change in muscle strength [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
Ankle strength will be assessed by the maximum isometric plantar flexion torque produced by the ankle and measured by a 6 degrees-of-freedom (DOF) load cell.
  • Change in muscle coordination [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Muscle coordination will be measured with surface electromyography (EMG). EMGs will be collected using a Zerowire Multichannel Electromyograph System [Aurion/Noraxon, Scottsdale, AZ]. These recordings will allow for the measurement of changes in muscle coordination.
  • Change in kinematics of the foot during overground walking [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Limb kinematics of the foot will be measured using high precision cameras [Optotrak Certus] during overground walking.
  • Change in forces produced during overground walking [ Time Frame: Baseline, immediately after intervention (day 1 and day 5), and at follow-ups (one week and two weeks) ]
    Ground reaction forces will be measured using a force platform [AMTI OR6-7-2000, Advanced Mechanical Technology Inc, USA] embedded into a floor for overground walking.
Not Provided
Not Provided
 
Effects of Caffeine and Low Oxygen Therapy on Leg Function in Human Spinal Cord Injury
The Effects of Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury (Caffeine Substudy)
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.

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 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. Saliva samples will be collected before and after the breathing intervention using a standard passive drool protocol to assess caffeine concentrations within the body. The subject will be asked to collect saliva in their mouth and drool into a vial.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Spinal Cord Injuries
  • Dietary Supplement: Caffeine
    Subjects will ingest capsules containing caffeine (up to 6mg/kg). Experiments will begin 60min after consumption to approximately coincide with peak plasma concentrations.Throughout the 60min wait time and experimentation, blood pressure and heart rate will be monitored.
  • Other: AIH
    Participants will breath 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) = 0.09±0.02 (hypoxia).
    Other Name: Acute intermittent hypoxia
  • Dietary Supplement: Placebo
    This is a placebo counterpart to the caffeine drug. Subjects will ingest capsules containing dextrose. Experiments will begin 60min after consumption to mimic the caffeine drug protocol.Throughout the 60min wait time and experimentation, blood pressure and heart rate will be monitored.
  • Active Comparator: Caffeine/AIH
    Subjects with chronic, motor-incomplete SCI receive Caffeine and AIH
    Interventions:
    • Dietary Supplement: Caffeine
    • Other: AIH
  • Active Comparator: Placebo/AIH
    Subjects with chronic, motor-incomplete SCI receive Placebo and AIH
    Interventions:
    • Other: AIH
    • Dietary Supplement: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
Same as current
May 2020
May 2020   (Final data collection date for primary outcome measure)

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 T12 with non-progressive etiology
  • classified as motor-incomplete with visible volitional leg movement
  • injury greater than 1 year

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
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Older Adult)
Yes
Contact: Randy D Trumbower, PT, PhD (617) 952-6951 randy.trumbower@mgh.harvard.edu
Contact: Lorna Brown, DPT (617) 952-6950 labtrumbower@gmail.com
United States
 
 
NCT02323698
2017P001940b
1R01HD081274 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
Randy Trumbower, PT, PhD, Harvard Medical School
Spaulding Rehabilitation Hospital
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Foundation Wings For Life
Principal Investigator: Randy D Trumbower, PT, PhD Harvard Medical School
Spaulding Rehabilitation Hospital
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP