Biologic Mechanisms of Early Exercise After Intracerebral Hemorrhage

Study Overview
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Brief Summary
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This study aims to determine whether in-bed cycle ergometry, early in the hospital course after a brain hemorrhage could balance damaging and reparative inflammation in the brain. Inflammatory factors of two groups of patients with brain hemorrhage will be compared, one group will receive in-bed cycling beginning 3 days after hemorrhage plus usual care and the other group will receive usual care only.

Official Title
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Biologic Mechanisms of Early Exercise After Intracerebral Hemorrhage: a Pilot Randomized Controlled Trial of Cycle Ergometry

Conditions
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Intra Cerebral Hemorrhage, Stroke Hemorrhagic

Intervention / Treatment
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* Device: Supine cycle ergometry of the lower extremities


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Supratentorial intracerebral hemorrhage with or without intraventricular hemorrhage Pre-morbid modified Rankin Score of 0-2 Patient must be able to provide informed consent or have a legally authorized representative to provide consent on patient's behalf Exclusion Criteria: Patients with known inflammatory conditions, infection requiring antibiotics or pregnancy Patients receiving daily anti-inflammatory medications including but not limited to prednisone, methotrexate, non-steroidal anti-inflammatory medications (ibuprofen, naproxen, indomethacin, celecoxib) and aspirin >325mg Glasgow Coma Score (GCS) 3 48 hours after admission Patients in whom withdrawal of life support is being considered by surrogate decision makers Injury to the lower extremities, hips or pelvis, weight >250 kg (weight limit of cycle), or body habitus precluding normal function of cycle

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot randomized parallel group design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supine cycle ergometry of the lower extremities<br>Patients will receive two 20 minute cycle ergometry sessions separated by at least 4 hours in addition to usual care. The cycle will be set to a gear of zero and will begin in passive mode, the patient will be able to actively cycle if patients are able. | Device: Supine cycle ergometry of the lower extremities<br>* The cycle ergometer allows for movement of the lower extremities by a motor if a patient is experiencing a disorder of consciousness or is otherwise unable to move one or both legs. If a patient is able to cycle actively the device allows the patient to move patient's legs without support of the motor.<br>|
| No Intervention: Control<br>Patients will receive usual care only. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in interleukin-1beta level in blood (picogram/milliliter) |  | Day 1, day 3 and day 7 of study | 
| Change in Interleukin-6 level in blood (picogram/milliliter) |  | Day 1, day 3 and day 7 of study | 
| Change in Tumor Necrosis Factor-alpha level in blood (picogram/milliliter) |  | Day 1, day 3 and day 7 of study | 
| Change in C Reactive Protein level in blood (nanogram/milliliter) |  | Day 1, day 3 and day 7 of study | 
| Change in Brain Derived Neurotrophic Factor level in blood (picogram/milliliter) |  | Day 1, day 3 and day 7 of study | 
| Change in interleukin-1beta level in cerebrospinal fluid (picogram/milliliter) | Cerebrospinal fluid (CSF) will be collected only in patients with an external ventricular drain as part of patients' care. | Day 1, day 3 and day 7 of study | 
| Coefficient of correlation between interleukin-1beta level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1 of study | 
| Coefficient of correlation between interleukin-1beta level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care. | Day 3 of study | 
| Coefficient of correlation between interleukin-1beta level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 7 of study | 
| Change in Interleukin-6 level in CSF (picogram/milliliter) | CSF will be collected only in patients with an external ventricular drain as part of patients' care. | Day 1, day 3 and day 7 of study | 
| Coefficient of correlation between Interleukin-6 level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care. | Day 1 of study | 
| Coefficient of correlation between Interleukin-6 level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care. | Day 3 of study | 
| Coefficient of correlation between Interleukin-6 level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care. | Day 7 of study | 
| Change in tumor Necrosis Factor-alpha level in CSF (picogram/milliliter) | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1, day 3 and day 7 of study | 
| Coefficient of correlation between tumor Necrosis Factor-alpha level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1 of study | 
| Coefficient of correlation between tumor Necrosis Factor-alpha level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 3 of study | 
| Coefficient of correlation between tumor Necrosis Factor-alpha level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 7 of study | 
| Change in C Reactive Protein level in CSF (nanogram/milliliter) | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1, day 3 and day 7 of study | 
| Coefficient of correlation between C Reactive Protein level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1 of study | 
| Coefficient of correlation between C Reactive Protein level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 3 of study | 
| Coefficient of correlation between C Reactive Protein level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 7 of study | 
| Change in Brain Derived Neurotrophic Factor level in CSF (picogram/milliliter) | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1, day 3 and day 7 of study | 
| Coefficient of correlation between Brain Derived Neurotrophic Factor levels in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 1 of study | 
| Coefficient of correlation between Brain Derived Neurotrophic Factor level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 3 of study | 
| Coefficient of correlation between Brain Derived Neurotrophic Factor level in CSF and blood | CSF will be collected only in patients with an external ventricular drain as part of patients' care | Day 7 of study | 
| Change in salivary cortisol level (microgram/deciliter) |  | Day 1, day 3 and day 7 of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hand-held dynamometry score (pounds) | An average of three hand-held dynamometry measurements will be calculated for each measurement episode and the change over time will be measured. | Daily on study days 1-7 | 
| Hand-held dynamometry score (pounds) | An average of three hand-held dynamometry measurements will be calculated. | On the day of transfer from the ICU or discharge, whichever comes first, assessed up to 60 days | 
| Hand-held dynamometry score (pounds) | An average of three hand-held dynamometry measurements will be calculated. | At 30-day follow-up visit | 
| Global pre-morbid physical health status as measured by the Promis Scale v1.2 | The global physical health status subscale of the Promis scale v1.2 will be used to measure pre-morbid physical health status. A 5-point Likert scale is used to score each of the four items. The scores for each item are summed as a raw score and are converted to T scores using a standardized table with higher T scores indicating better physical health status. | Day 1 of study | 
| Global pre-morbid mental health status as measured by the Promis Scale v1.2 | The global mental health status subscale of the Promis scale will be used to measure pre-morbid mental health status. A 5-point Likert scale is used to score each of the four items. The scores for each item are summed as a raw score and are converted to T scores using a standardized table with higher T scores indicating better mental health status. | Day 1 of study | 
| Global pre-morbid pain status as measured by the Promis Scale v1.2 | The pain subscale of the Promis scale of global health will be used to measure pre-morbid pain status. A 10 point visual analog scale is used with higher scores indicating greater pain levels. Raw scores will be used for analysis. | Day 1 of study | 
| Global pre-morbid fatigue as measured by the Promis Scale v1.2 | The fatigue subscle of the Promis scale of global health will be used to measure pre-morbid fatigue status. A 5 point Likert scale is used with higher scores indicating no fatigue and lower scores indicating increasing levels of fatigue. Raw scores will be used for analysis. | Day 1 of study | 
| Functional status as assessed by the Modified Rankin Score | The modified Rankin score will be used to measure function in terms of activities of daily living after stroke. A six-point ordinal scale (0-6) with lower scores indicating less disability and higher scores indicating increasingly severe disability. A score of 6 indicates death. | On transfer from the ICU or discharge from the hospital, whichever comes first, assessed up to 60 days | 
| Functional status as assessed by the Modified Rankin Score | The modified Rankin score will be used to measure function in terms of activities of daily living after stroke. A six-point ordinal scale (0-6) with lower scores indicating less disability and higher scores indicating increasingly severe disability. A score of 6 indicates death. | During the 30-day follow-up visit | 
| Change in muscle strength as assessed by the Medical Research Council Sum (MRCS) Score | The MRCS will be used to measure muscle strength over time. The instrument is a 60 point scale indicating muscle strength in 6 muscle groups. Three muscle groups each on the right and left upper extremities and three each in the right and left lower extremities. Each muscle group is scored from 0-5 out of a possible 5 points. A composite score with a maximum of 60 is produced, 30 points can be achieved for each side of the body. | Daily on study days 1-7 | 
| Muscle strength as assessed by the Medical Research Council Sum (MRCS) Score | The MRCS will be used to measure muscle strength. The instrument is a 60 point scale indicating muscle strength in 6 muscle groups. Three muscle groups each on the right and left upper extremities and three each in the right and left lower extremities. Each muscle group is scored from 0-5 out of a possible 5 points. A composite score with a maximum of 60 is produced, 30 points can be achieved for each side of the body. | On transfer from the ICU or discharge from the hospital, whichever comes first, assessed up to 60 days | 
| Muscle strength as assessed by the Medical Research Council Sum (MRCS) Score | The MRCS will be used to measure muscle strength. The instrument is a 60 point scale indicating muscle strength in 6 muscle groups. Three muscle groups each on the right and left upper extremities and three each in the lower extremities. Each muscle group is scored from 0-5 out of a possible 5 points. A composite score with a maximum of 60 is produced, 30 points can be achieved for each side of the body. | During the 30-day follow-up visit | 
| Ability to perform activities of daily living as assessed by the Barthel Index | The Barthel index will be used to measure a participant's ability to perform activities of daily living in detail. The instrument is a 10-item scale with a maximum of 100 points. Higher scores indicate higher levels of function. | On transfer from the ICU or discharge from the hospital, whichever comes first, assessed up to 60 days | 
| Ability to perform activities of daily living as assessed by the Barthel Index | The Barthel index will be used to measure a participant's ability to perform activities of daily living in detail. The instrument is a 10-item scale with a maximum of 100 points. Higher scores indicate higher levels of function. | During the 30-day follow-up visit | 
| Health status as assessed by the Stroke Impact Scale version 3.0 | This is a 59-item questionnaire that will measure health status in 8 domains following the stroke. A 5-point Likert scale is used to score each item with higher scores indicating higher perceived health status. | During the 30-day follow up visit | 
| Perception of stroke recovery as assessed by the Stroke Impact Scale version 3.0 | The last question of the instrument measures a participant's perception of stroke recovery using a 0-100 scale with higher scores representing higher levels of recovery and lower scores representing less recovery. | During the 30-day follow up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rehabilitation, cycle ergometry