Stroke
Conditions
Brief summary
Of the 795,000 people who experience a stroke every year in the US, only a small percentage will achieve full recovery. While current therapies promote strength and endurance, none directly address the unique potential of the brain to reorganize following injury. The goal of this project is to explore the effects of a novel therapy, acute intermittent hypoxia (AIH). During this therapy, individuals receive brief bouts of reduced oxygen levels by inhalation through a face mask. (This is akin to being on top of a tall mountain). In brief exposures, AIH is known to trigger the release of specific proteins that help the brain adapt to oxygen reductions. Published results in people with incomplete spinal cord injury have shown that AIH enhances muscle strength and coordination rather quickly. The research team aims to study the effects of AIH in stroke survivors.
Detailed description
Stroke is the second leading cause of death and a leading cause of long-term disability worldwide. Despite the spontaneous recovery that occurs following a hemispheric stroke, more than half of stroke patients show substantial residual impairments, imposing a significant human and economic burden. This burden is likely to increase in coming decades, due to a rapidly aging population, and the associated progression of cardiovascular risk factors. Accordingly, new interventions to alleviate impairment in stroke survivors are urgently needed. The development and testing of one such novel intervention, termed Acute Intermittent Hypoxia (AIH), is the primary focus of this AHA Innovative Project Award. The aim is to answer questions related to safety and preliminary efficacy of AIH in stroke survivors. First, the Investigators will establish whether brief reductions in inhaled oxygen concentration can be safely tolerated in stroke survivors. A clinician will closely monitor subjects for any adverse events. The second aim is to establish the effects of AIH on elbow flexion/extension strength, and on hand grip and pinch strength. Subjects will be monitored closely for any adverse events during these experiments. Data will be analyzed to determine if there is an improvement in key outcomes at any dose level.
Interventions
An oxygen monitor will continuously measure and record the fraction of inspired oxygen delivered to the subject. Inspired fraction of oxygen (FiO2) of the gas mixture will be individually adjusted using the valve settings to reach the targeted SpO2. The gas mixtures administered during the four sessions will be 21% O2 (target SpO2 = 95%), 17% O2 (target SpO2 = 92%), 13% O2 (target SpO2 = 87%) and 9% O2 (target SpO2 = 82%).
Sponsors
Shirley Ryan AbilityLab
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age ≥18 years; A first time, unilateral, ischemic, hemispheric stroke, confirmed by magnetic resonance imaging (MRI); Chedoke assessment \> 3 Ability to open and close affected hand Able to understand and communicate in English Be able to consent independently ≥ 6 months post stroke Must have a hemoglobin level above 10g/dl (to be confirmed using handheld noninvasive lab equipment) Must have ability to attend research visits with a companion for assistance WOCBP must be comfortable confirming negative pregnancy prior to hypoxia experimental therapy.
Exclusion criteria
Brain stem or cerebellar stroke; mean Fazekas score rated on initial fluid-attenuated inversion recovery MRI ≥3 Severe aphasia, preventing subject from understanding the protocol and giving written consent; History of prior neurological disorder; Pre-existing hypoxic pulmonary disease, Severe hypertension (\>160/100) Ischemic cardiac disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 6 days | All adverse events will be reviewed for safety and study continuation by the medical monitor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| National Institute of Health Stroke Scale (NIHSS) | Baseline and Day 6 | is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score ranging from 0-44. A change from baseline to follow up 1 (day 6) is reported, calculated from: value at day 6 - value at baseline |
| Fugl- Meyer Assessment | Baseline, Day 6 | Each test element will be graded on a 3-point ordinal scale and summed up to provide a maximum upper limb score of 66. Reliability and validity have been demonstrated. The FMA will be administered while the subject is seated. A score of 0 indicates no upper extremity function or reflexes, a score of 66 indicates complete control of the paretic upper extremity. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| Modified Ashworth Scale | Baseline, Day 6 | This scale allows for characterization of increases in muscle tone, from low or normal tone to complete limb rigidity. Specifically, we will evaluate the elbow flexors, bilaterally. A score of zero indicates no residual muscle spasticity, a score of 4 is a completely rigid limb with no possible movement. Each participant had their stroke affected elbow joint tested. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| Grip Strength | Baseline, Day 6 | A dynamometer measures maximum gross grasp (lb.) averaged over three attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. Completed bilaterally, if possible The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| Pinch Strength | Baseline, Day 6 | Hydraulic Handheld Dynamometer): A dynamometer measures maximum gross grasp (lb.) averaged over 3 attempts with each hand. The minimum possible value of zero lb. will be assigned when the participant cannot actively flex the fingers or grasp the dynamometer. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| Elbow Strength | Baseline, Day 6 | monitoring changes in isometric elbow flexion force using a dynamometer. A total of three trials will be taken on each side, with a rest break between trials. The average of the three trials will be recorded. Strength recorded in lbs, with a minimum value of zero. The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| D-KEFS Color-Word Interference Test | Baseline, Day 6 | A neuropsychological measure that seeks to evaluate attention and inhibition. Subjects will be asked to read words or name ink colors as quickly as possible within a given time limit. The test supplies the examiner with three separate scores, including an ability to calculate an interference score. This final score allows for interpretation of cognitive flexibility, creativity and cognitive stress. This measure will be utilized to monitor subjects throughout their participation at specific time-points. Audio recording may be taken to ensure accurate recording of responses. The scale is from 1-18, with 10 being at expected level,. A score below 10 is worse performance than expected, and a score above 10 is greater than expected level. The score reported here is the change in score between Day 6 and baseline The values reported are differences from follow up (Day 6) and baseline calculated as: value at day 6 - value at baseline |
| 5 Minute Neurological Test | Baseline, day 6 | Quick short tests to assess clinical status performed by physician to ensure no change in neurologic status, The values reported are the count of participants who were found to have no change in neurolgical status from baseline to day 6 by the clinician |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORZev Rymer, MD/PhD
Principal Investigator
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.75 years STANDARD_DEVIATION 6.4 |
| Chedoke McMaster Hand Score | 4.5 units on a scale STANDARD_DEVIATION 1.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
| Time since Stroke Onset | 9.03 years STANDARD_DEVIATION 7.16 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 4 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
None listed