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

NCT02323698 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2017P001940b5R01HD081274
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries

Keywords

hypoxia; spinal cord injury; rehabilitation; strength; walk; function; low oxygen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 6 Minute Walk Test

  Baseline, after intervention (day 5), and at follow-ups (one week and two weeks)

Study Arms (3)

Caffeine/AIH

ACTIVE COMPARATOR

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

Drug: Caffeine; Other: AIH

Placebo/AIH

ACTIVE COMPARATOR

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

Other: AIH; Other: Placebo

Caffeine/SHAM

ACTIVE COMPARATOR

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

Drug: Caffeine; Other: SHAM

Interventions

Caffeine DRUG

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.

Also known as: caffeine anhydrous

Caffeine/AIH; Caffeine/SHAM

AIH OTHER

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.

Also known as: Acute intermittent hypoxia

Caffeine/AIH; Placebo/AIH

Placebo OTHER

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.

Placebo/AIH

SHAM OTHER

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.

Caffeine/SHAM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, 02138, United States

Location

Related Publications (6)

• 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.

  PMID: 30009669 BACKGROUND

• 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.

  PMID: 29648987 BACKGROUND

• 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.

  PMID: 28972191 BACKGROUND

• 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.

  PMID: 28762876 BACKGROUND

• 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.

  PMID: 24618214 BACKGROUND

• 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.

  PMID: 24285617 BACKGROUND

Related Links

• INSPIRE Lab Website

MeSH Terms

Conditions

Spinal Cord Injuries; Hypoxia

Interventions

Caffeine; Insemination, Artificial, Homologous; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Insemination, Artificial; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Insemination; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Results Point of Contact

• Title: Dr. Randy D Trumbower, PI
• Organization: Spaulding Rehabilitation Hospital

randy.trumbower@mgh.harvard.edu

(617) 952-6953

Study Officials

• Randy D Trumbower, PT, PhD

  Harvard Medical School (HMS and HSDM)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Balanced design

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 23, 2014
• Study Start: January 1, 2019
• Primary Completion: March 19, 2021
• Study Completion: February 19, 2022
• Last Updated: December 13, 2023
• Results First Posted: August 9, 2022

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)