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

Spinal Cord Injuries Clinical Trial

Official title:

The Effects of Intermittent Hypoxia on Leg Function in Human Spinal Cord Injury (Caffeine Substudy)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02323698
• Other study ID #: 2017P001940b
• Secondary ID: 5R01HD081274
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 1, 2019
• Est. completion date: February 19, 2022

Study information

• Verified date: December 2023
• Source: Spaulding Rehabilitation Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 19, 2022
• Est. primary completion date: March 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypoxia
• Spinal Cord Injuries
• Wounds and Injuries

Intervention

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:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Spaulding Rehabilitation Hospital	Cambridge	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Spaulding Rehabilitation Hospital	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Hayes HB, Chvatal SA, French MA, Ting LH, Trumbower RD. Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury. Clin Neurophysiol. 2014 Oct;125(10):2024-35. doi: 10.1016/j.clinph.2014.02.001. Epub 2014 Feb 14. — View Citation

Hayes HB, Jayaraman A, Herrmann M, Mitchell GS, Rymer WZ, Trumbower RD. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13. doi: 10.1212/01.WNL.0000437416.34298.43. Epub 2013 Nov 27. — View Citation

Peters DM, Thibaudier Y, Deffeyes JE, Baer GT, Hayes HB, Trumbower RD. Constraints on Stance-Phase Force Production during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Feb 1;35(3):467-477. doi: 10.1089/neu.2017.5146. Epub 2017 Oct 27. — View Citation

Sohn WJ, Tan AQ, Hayes HB, Pochiraju S, Deffeyes J, Trumbower RD. Variability of Leg Kinematics during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma. 2018 Nov 1;35(21):2519-2529. doi: 10.1089/neu.2017.5538. Epub 2018 Jun 5. — View Citation

Trumbower RD, Hayes HB, Mitchell GS, Wolf SL, Stahl VA. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology. 2017 Oct 31;89(18):1904-1907. doi: 10.1212/WNL.0000000000004596. Epub 2017 Sep 29. — View Citation

Trumbower RD. Stimulating the Injured Spinal Cord: Plenty to Grasp. J Neurotrauma. 2018 Sep 15;35(18):2143-2144. doi: 10.1089/neu.2018.5993. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	10 Meter Walk Time	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	6 Minute Walk Test	Measure participant's distance walked in 6 minutes (meters).	Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)

External Links

•   INSPIRE Lab Website