Impact of Intermittent Hypoxia and Prednisolone on Motor Performance in Persons With SCI

The objective of this study is to examine the effects of mild acute intermittent hypoxia (AIH) in combination with an anti-inflammatory drug (i.e. prednisolone) on motor performance in persons with spinal cord injury (SCI).

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: Prednisolone + Acute Intermittent Hypoxia; Other: Placebo + Acute Intermittent Hypoxia

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Spinal cord lesion at the level of C4 or below.
• Incomplete spinal cord injury ASIA (American Spinal Injury Association) Impairment Scale classification C or D. ASIA C or D classification requires that individuals have detectable motor function below the level of spinal injury and have preserved sensation of the sacral segments S4-S5 (anal sphincter).
• Age between 18 and 65 years.
• Medically stable with medical clearance to participate.
• SCI due to non-progressive etiology.
• More than 6 months since initial SCI. We plan to choose subjects greater that six months post-injury, to ensure minimal confounding effects of spontaneous neurological recovery during the experiments. This will mean that changes in motor performance are due to the interventions associated with the research study.
• Subjects must have active and passive ROM at the ankle from 10 degrees dorsiflexion to 30 degrees plantar flexion, 0 to 120 degrees of knee flexion, 90 degrees of hip flexion, and 10 degrees of hip extension in order to be positioned correctly for motor performance testing.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Presence of severe medical illness, including cardiac disease, uncontrolled high blood pressure, restrictive or obstructive pulmonary disease, significant osteoporosis or history of fracture following SCI, or history of lower limb peripheral nerve injury.
• Individuals with uncontrolled diabetes mellitus, unhealed decubitus ulcers, active heterotopic ossification, rheumatologic disease or inflammatory arthritis, presence of a deep venous thrombosis, cancer, or active infection will be excluded, as these conditions can cause systemic inflammation independent of spinal cord injury.
• Patients may not be receiving any other investigational agents.
• Individuals with tracheostomy, asthma, or recent or current pulmonary infection will be excluded.
• Women who are pregnant or nursing will be excluded, as the potential effects of intermittent hypoxia on pregnant women and fetus are unknown.
• Subjects will also be excluded if they are currently taking NSAIDs, steroids, or disease-modifying anti-rheumatic drugs (DMARDs). Participation is allowed if the subject and his/her physician agree to suspend all NSAIDs for a minimum of a 14-day washout period prior to study evaluation and for the duration of the study. Individuals taking oral steroids, DMARDs will be excluded from the study due to the potential risks of abruptly discontinuing these agents.
• Individuals will be excluded if they have a history of severe adverse reaction or allergic response to prednisolone in the past, history of stomach or intestinal ulcers, bleeding problems, chronic kidney disease, drink more than 3 alcoholic beverages per day, or are currently taking blood thinners. Excluding these individuals will limit the potential for having an adverse reaction to the anti-inflammatory administered in the study.
• Individuals receiving intrathecal baclofen will be excluded. Individuals prescribed medications other than intrathecal baclofen for alleviation of spastic motor behaviors will be excluded unless both the subject and his/her physician agree to cease all such medications for a 14-day minimum washout period prior to participation and for the duration of the study.
• Individuals will be excluded if they are taking antifungal ointments, estradiols or estrogens, rifampin, phenytoin, barbiturates or bupropion as these drugs can potential interact with prednisolone. See "concomitant medications" section below.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisolone + Acute Intermittent Hypoxia	Other: Prednisolone + Acute Intermittent Hypoxia; Administration of oral prednisolone followed by 15, 60-second bouts of mild hypoxia
Placebo Comparator: Placebo + Acute Intermittent Hypoxia	Other: Placebo + Acute Intermittent Hypoxia; Administration of oral matching placebo followed by 15, 60-second bouts of mild hypoxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Isometric Ankle Plantar Flexion strength	60 minutes

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab

Publications and helpful links

General Publications

• Sandhu MS, Gray E, Kocherginsky M, Jayaraman A, Mitchell GS, Rymer WZ. Prednisolone Pretreatment Enhances Intermittent Hypoxia-Induced Plasticity in Persons With Chronic Incomplete Spinal Cord Injury. Neurorehabil Neural Repair. 2019 Nov;33(11):911-921. doi: 10.1177/1545968319872992. Epub 2019 Sep 15.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: November 21, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 26, 2018

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: November 21, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Signs and Symptoms, Respiratory; Spinal Cord Diseases; Spinal Cord Injuries; Hypoxia; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: STU00103487

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: No
• Studies a U.S. FDA-regulated device product: No