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Trial record 1 of 1 for:    NCT02323698
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Effects of Caffeine and Intermittent Hypoxia 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 : July 23, 2020
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

Tracking Information
First Submitted Date  ICMJE December 18, 2014
First Posted Date  ICMJE December 23, 2014
Last Update Posted Date July 23, 2020
Study Start Date  ICMJE October 2014
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
Change in overground walking speed [ Time Frame: Baseline after intervention (day 5), and at follow-ups (one week and two weeks) ]
Speed will be assessed by the time required to walk 10 meters (10MWT).
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2014)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Caffeine and Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury
Official Title  ICMJE The Effects of Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury (Caffeine Substudy)
Brief 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, caffine+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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Balanced design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Spinal Cord Injuries
Intervention  ICMJE
  • Drug: Caffeine
    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.
    Other Name: caffeine anhydrous
  • Other: AIH
    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.
    Other Name: Acute intermittent hypoxia
  • Other: Placebo
    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.
  • Other: SHAM
    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.
Study Arms  ICMJE
  • Active Comparator: Caffeine/AIH
    Subjects with chronic, motor-incomplete SCI receive Caffeine then AIH
    Interventions:
    • Drug: Caffeine
    • Other: AIH
  • Active Comparator: Placebo/AIH
    Subjects with chronic, motor-incomplete SCI receive Placebo then AIH
    Interventions:
    • Other: AIH
    • Other: Placebo
  • Active Comparator: Caffeine/SHAM
    Subjects with chronic, motor-incomplete SCI receive Caffeine then SHAM
    Interventions:
    • Drug: Caffeine
    • Other: SHAM
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 18, 2014)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Randy D Trumbower, PT, PhD (617) 952-6951 randy.trumbower@mgh.harvard.edu
Contact: Stella Barth, BA (617) 952-6822 SBARTH@PARTNERS.ORG
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02323698
Other Study ID Numbers  ICMJE 2017P001940b
5R01HD081274 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital
Study Sponsor  ICMJE Spaulding Rehabilitation Hospital
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: Randy D Trumbower, PT, PhD Harvard Medical School
PRS Account Spaulding Rehabilitation Hospital
Verification Date July 2020

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