CNS Growth Factors Release and Changes in the Inflammatory Environment in Response to Electrical Stimulation in Subjects With Inflammatory Myelopathies

Study Overview
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Brief Summary
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This research is being done to see how different amounts of Functional Electrical Stimulation (FES) affect cycling on factors in blood and spinal cord in people with spinal cord inflammation.

Detailed Description
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FES cycling is a method of applying low level electrical currents to the leg and buttock muscles to cause the weakened or paralyzed muscles to contract and produce a cycling motion of the legs. The FES cycling in this study will be done through a device called the RT300-SL Cycle Ergometer (RT300). Although this device has been cleared by the Food and Drug Administration (FDA) for use by individuals with neurological disorders, we are trying to find out the best way to use it in order to obtain the greatest results.

Official Title
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CNS Growth Factors Release and Changes in the Inflammatory Environment in Response to Electrical Stimulation in Subjects With Inflammatory Myelopathies

Conditions
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Inflammatory Myelopathies

Intervention / Treatment
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* Device: FES Cycling
* Device: Cycling without FES
* Procedure: Lumbar puncture
* Behavioral: Mood assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, Female, age 18-65, all ethnic groups History of inflammatory myelopathy with onset at least 3 months prior No FES ergometer (i.e. RT300 or equivalent) use within 1 month Subject is medically stable, with no recent (1 month or less) inpatient admission for acute medical or surgical issues Subject is legally able to make own health care decisions Access to telephone with texting capabilities English language proficiency Exclusion Criteria: Cardiovascular disease as defined by previous myocardial infarction, unstable angina, requirement for anti platelet agents, congestive heart failure, or stroke New York Heart Association (NYHA) Class III or IV, history of arrhythmia with hemodynamic instability. Uncontrolled hypertension (resting systolic BP>160mmHg or diastolic BP >100mmHg consistently) Concurrent lower motor neuron disease such as peripheral neuropathy that would exclude lower extremity electrical excitability Unstable long bone fractures of the lower extremities Subjects who are unwilling to agree to two cerebrospinal fluid (CSF) examinations (lumbar punctures) Presence of cardiac pacemaker and/or defibrillator Presence of cancer History of epileptic seizures Subjects having a Stage 2 or greater sacral decubitus ulcer Women who are pregnant Active drug or alcohol use or dependence

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>For 3 weeks, you will need to come to the International Center for Spinal Cord Injury at Kennedy Krieger Institute (ICSCI) one (1) time per week during which you will perform FES cycling for 1 hour each. | Device: FES Cycling<br>* You will be seated in your own wheelchair in front of the cycle. We will place your legs onto the cycle and secure them with straps. Electrodes (pads that stick to the skin) will be placed on your skin on your legs and buttock. The pads will be connected to a stimulator box through a wire. We will then start the cycle motor and stimulate your leg and buttock muscles with electric current. This will cause your legs to cycle. You will do this for 1 hour.<br>* Other names: RT300-SL, from Restorative Therapies, INC.;Procedure: Lumbar puncture<br>* The study includes 2 lumbar punctures: one at the beginning of the study and one at the end. During a lumbar puncture a small needle will be inserted into the lower back and a small amount of spinal fluid will be drained (about 1 tablespoon).<br>* Other names: Spinal Tap;Behavioral: Mood assessment<br>* If you do not already have an account, you will be signed up with Mood24/7 (http://www.mood247.com). This is a free service that texts your mobile phone daily asking you to rate your mood on a scale of 1 (low) through 10 (high). We will not monitor your entries during the study but only at the final visit when we will get a printout of the course of your mood during the study. After completion of the study we will assist you in removing us from your Mood24/7 account and we will no longer have access to your mood reports outside of the study period.<br>* Other names: Mood24/7;|
| Experimental: Group B<br>For 3 weeks, you will need to come to the ICSCI three (3) times per week during which you will perform FES cycling for 1 hour each. | Device: FES Cycling<br>* You will be seated in your own wheelchair in front of the cycle. We will place your legs onto the cycle and secure them with straps. Electrodes (pads that stick to the skin) will be placed on your skin on your legs and buttock. The pads will be connected to a stimulator box through a wire. We will then start the cycle motor and stimulate your leg and buttock muscles with electric current. This will cause your legs to cycle. You will do this for 1 hour.<br>* Other names: RT300-SL, from Restorative Therapies, INC.;Procedure: Lumbar puncture<br>* The study includes 2 lumbar punctures: one at the beginning of the study and one at the end. During a lumbar puncture a small needle will be inserted into the lower back and a small amount of spinal fluid will be drained (about 1 tablespoon).<br>* Other names: Spinal Tap;Behavioral: Mood assessment<br>* If you do not already have an account, you will be signed up with Mood24/7 (http://www.mood247.com). This is a free service that texts your mobile phone daily asking you to rate your mood on a scale of 1 (low) through 10 (high). We will not monitor your entries during the study but only at the final visit when we will get a printout of the course of your mood during the study. After completion of the study we will assist you in removing us from your Mood24/7 account and we will no longer have access to your mood reports outside of the study period.<br>* Other names: Mood24/7;|
| Experimental: Group C<br>For 3 weeks, you will need to come to the ICSCI five (5) times per week during which you will perform FES cycling for 1 hour each. | Device: FES Cycling<br>* You will be seated in your own wheelchair in front of the cycle. We will place your legs onto the cycle and secure them with straps. Electrodes (pads that stick to the skin) will be placed on your skin on your legs and buttock. The pads will be connected to a stimulator box through a wire. We will then start the cycle motor and stimulate your leg and buttock muscles with electric current. This will cause your legs to cycle. You will do this for 1 hour.<br>* Other names: RT300-SL, from Restorative Therapies, INC.;Procedure: Lumbar puncture<br>* The study includes 2 lumbar punctures: one at the beginning of the study and one at the end. During a lumbar puncture a small needle will be inserted into the lower back and a small amount of spinal fluid will be drained (about 1 tablespoon).<br>* Other names: Spinal Tap;Behavioral: Mood assessment<br>* If you do not already have an account, you will be signed up with Mood24/7 (http://www.mood247.com). This is a free service that texts your mobile phone daily asking you to rate your mood on a scale of 1 (low) through 10 (high). We will not monitor your entries during the study but only at the final visit when we will get a printout of the course of your mood during the study. After completion of the study we will assist you in removing us from your Mood24/7 account and we will no longer have access to your mood reports outside of the study period.<br>* Other names: Mood24/7;|
| Experimental: Group D<br>For 3 weeks, you will need to come to the ICSCI three (3) times per week during which you will perform cycling without FES for 1 hour each. | Device: Cycling without FES<br>* You will be seated in your own wheelchair in front of the cycle. We will place your legs onto the cycle and secure them with straps. The cycle is configured to work without FES. We will then start the cycle motor. This will cause your legs to cycle. You will do this for 1 hour.<br>* Other names: RT300-SL, from Restorative Therapies, INC.;Procedure: Lumbar puncture<br>* The study includes 2 lumbar punctures: one at the beginning of the study and one at the end. During a lumbar puncture a small needle will be inserted into the lower back and a small amount of spinal fluid will be drained (about 1 tablespoon).<br>* Other names: Spinal Tap;Behavioral: Mood assessment<br>* If you do not already have an account, you will be signed up with Mood24/7 (http://www.mood247.com). This is a free service that texts your mobile phone daily asking you to rate your mood on a scale of 1 (low) through 10 (high). We will not monitor your entries during the study but only at the final visit when we will get a printout of the course of your mood during the study. After completion of the study we will assist you in removing us from your Mood24/7 account and we will no longer have access to your mood reports outside of the study period.<br>* Other names: Mood24/7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSF BDNF Levels in Subjects With Inflammatory Myelopathy | We will measure cerebrospinal fluid (CSF) concentrations of BDNF in response to FES ergometry. We will investigate whether there is a correlation between plasma and CSF BDNF concentrations. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mood Assessment | We will assess mood daily on a Likert scale from 1 (low) to 10 (high) using Mood24/7. | 3 weeks | 
| Spasticity Testing Using the Modified Ashworth Scale (MAS) | The MAS is a widely used neurological rating scale, ranging from 0 (normal) to 5. It measures neurological impairment and disability based on the ratings of an observer or neurologist through structured definitions. | Baseline | 
| CSF Growth Factor Quantification | We will measure CSF concentrations of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, IL-1ß, IL-23, and IL-12 in response to FES ergometry. | Baseline | 
| Serum Brain Derived Neurotrophic Factor (BDNF) Level | We will quantify levels of BDNF in the serum/blood using immunohistochemical quantification methods | Baseline | 
| Spasticity Testing Using the Modified Ashworth Scale (MAS) | The MAS is a widely used neurological rating scale, ranging from 0 (normal) to 5. It measures neurological impairment and disability based on the ratings of an observer or neurologist through structured definitions | 3 weeks | 
| CSF Growth Factor Quantification | We will measure CSF concentrations of IL-6, IL-17, TNF-α, IL-1ß, IL-23, and IL-12 in response to FES ergometry. | 3 weeks | 
| Serum Brain Derived Neurotrophic Factor (BDNF) Level | We will quantify levels of BDNF in the serum/blood using immunohistochemical quantification methods. | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TM, MS, Spinal Cord Injury, Functional electrical stimulation, Rehabilitation, Growth factors, Cytokines