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

December 11, 2023 updated by: Randy Trumbower, PT, PhD, Spaulding Rehabilitation Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02138
        • Spaulding Rehabilitation Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Caffeine/AIH
Subjects with chronic, motor-incomplete SCI receive Caffeine then AIH
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 Names:
  • 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 Names:
  • Acute intermittent hypoxia
Active Comparator: Placebo/AIH
Subjects with chronic, motor-incomplete SCI receive Placebo then AIH
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 Names:
  • 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.
Active Comparator: Caffeine/SHAM
Subjects with chronic, motor-incomplete SCI receive Caffeine then SHAM
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 Names:
  • caffeine anhydrous
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
10 Meter Walk Time
Time Frame: Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)
Speed will be assessed using the time required to walk 10 meters (10MWT) relative to baseline.
Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6 Minute Walk Test
Time Frame: Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)
Measure participant's distance walked in 6 minutes (meters).
Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spaulding Rehabilitation Hospital

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Randy D Trumbower, PT, PhD, Harvard Medical School (HMS and HSDM)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Actual)

March 19, 2021

Study Completion (Actual)

February 19, 2022

Study Registration Dates

First Submitted

December 18, 2014

First Submitted That Met QC Criteria

December 18, 2014

First Posted (Estimated)

December 23, 2014

Study Record Updates

Last Update Posted (Estimated)

December 13, 2023

Last Update Submitted That Met QC Criteria

December 11, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017P001940b
  • 5R01HD081274 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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