Clinical trial NCT03998527: Non-Invasive Spinal Cord Stimulation After Injury
Official title: Non-Invasive Spinal Cord Stimulation and Respiratory Plasticity
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: Respiration
Motor control
Lead sponsor: University of Louisville
Sponsor class: OTHER
First posted: 2019-06-26
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to assess the function of the lungs and the muscles are used to breathe after individuals receive respiratory training, spinal cord stimulation, a combination of respiratory training and stimulation, a combination of arm training and stimulation, or a combination of trunk training and stimulation. The respiratory, arm, and trunk training combined with the spinal stimulation interventions are being used to activate the spinal cord below the level of injury. Investigators will be looking for changes in the function of the lungs and trunk muscles before, during, and after these task-specific and non-task-specific interventions for breathing to determine which one has the greatest effect. The results of this study may aid in the development of treatments to help individuals with spinal cord injuries that have impaired lung, arm, and trunk function.

Detailed description: Study Aim 1. This study is aimed to evaluate the effects of non-invasive transcutaneous electrical spinal-cord stimulation (TcESCS) applied below the neurological level of Spinal Cord Injury (SCI) on respiratory, upper extremity, and trunk functional and motor control properties and identify their underlying physiological mechanisms. Evaluation of the mechanisms of respiratory and motor control modulations evoked by the TcESCS will have important implications for the development of specific therapeutic strategies to fight complications of SCI. The objective of Aim 1 is to investigate whether TcESCS can significantly increase activation of motor networks. This work will be done by electrophysiological characterization of respiratory and other motor responses as assessed at rest and in response to the respiratory and other challenges in SCI individuals. Changes in functional measures will be assessed when the TcESCS device is turned "off" and "on". To evaluate "dose-dependent" effects, changes in surface electromyographic (sEMG) magnitude and muscle co-activation will be assessed when stimulation parameters and location are changed during respiratory efforts and motor tasks. The extent to which the stimulation is associated with the largest change in respiratory and sEMG parameters will be implemented as a strategy to be used during stimulation in combination with Respiratory Training (RT), Arm Training (AT), and Trunk Training (TT). To attain the objective of this aim, we will test the working hypothesis that TcESCS excites specific motor networks leading to amplified motor responses. We will test this hypothesis by applying TcESCS during our original approach of the Respiratory Motor Control Assessment (RMCA) and other sEMG-based assessments with kinematics to characterize respiratory, arm, and trunk motor function. During these assessments, beat-to-beat Blood Pressure/ Heart Rate (BP/HR), and respiratory rate will be recorded to evaluate respiratory-cardiovascular responses. The rationale for this aim is that successful completion of the proposed research will contribute fundamental elements to our basic knowledge, without which the therapeutic value of TcESCS cannot be understood. The acquisition of such knowledge is critical to the development of specific rehabilitative strategies. When the proposed studies for Aim 1 have been completed, we expect that motor and inter-related characteristics affected by TcESCS in patients with SCI will be established. Such findings would be important because it will allow us, for the first time, to evaluate the ability of non-invasive spinal cord stimulation to enhance the decreased state of spinal network activity thus demonstrating the potential for rehabilitation.

Study Aim 2. The goal is to evaluate the effectiveness and therapeutic mechanisms of the TcESCS combined with task-specific (Respiratory Training) and non-task-specific (Arm Training and Trunk Training) interventions for breathing. Identification of the physiological effects of potential rehabilitative approaches will have important implications for the development of specific therapeutic strategies. The objective of Aim 2 is to investigate the therapeutic effects of RT regimen in combination with TcESCS. This work will be done by using methods outlined in Aim 1 and additional clinical measures all assessed before training, and repeatedly during follow-up period. Working hypothesis that compare to RT alone and TcESCS alone, RT assisted by TcESCS leads to enhanced use-dependent plasticity of respiratory motor networks, leading the functional recovery will be tested by using the approach of detecting changes in respiratory and other motor control outcome measures in response to stimulation and training. The rationale for this aim is that successful completion of the proposed research will advance the field by providing new avenues for the application of activity-based therapy accompanied by the spinal cord stimulation. When the proposed studies for Aim 2 have been completed, it is expected that the rehabilitative capacity of RT with TcESCS will be determined. Such results are important, because, for the first time, identified therapeutic mechanisms of TcESCS will provide evidence that this intervention can enhance the effects of activity-based therapy in participants with SCI.

Eligibility criteria: All SCI research participants, irrespective of gender, will be selected based on the following:

Inclusion Criteria:

1. At least 18 years of age at the time of enrollment;
2. Stable medical condition;
3. Non-progressive SCI T5 or above;
4. Sustained SCI at least 12 months prior to enrollment;
5. At least a 15% deficit in pulmonary function outcomes (FVC or FEV1) as was detected by screening spirometry

Exclusion Criteria:

1. Untreated musculoskeletal dysfunction;
2. Unhealed fracture;
3. Untreated contracture or pressure sore;
4. Ventilator dependence;
5. Untreated depression, psychiatric disorder, or ongoing drug abuse;
6. Major pulmonary or cardiovascular disease;
7. Major esophageal or gastrointestinal disease;
8. Endocrine disorder, malignancy, marked obesity, deep vein thrombosis, or HIV/AIDS related illness;
9. Secondary causes of orthostatic hypotension (anemia, hypervolemia, endocrine, or neurological);
10. Pregnancy by self-report.

All Non-Disabled research participants, irrespective of gender, will be selected based on the following:

Inclusion Criteria:

1. At least 21 years of age at the time of enrollment.
2. FVC and FEV1 values 80% of predicted or above indicating healthy pulmonary function by screening spirometry.

Exclusion Criteria:

1. History of respiratory disease by self-report,
2. History of cardiovascular disease by self-report.

Primary outcomes:
measure: Non-invasive respiratory electromyography
timeFrame: Through study completion, an average of 1 year.
measure: Spirometry
timeFrame: Through study completion, an average of 1 year.
measure: Maximum airway pressure
timeFrame: Through study completion, an average of 1 year.
Secondary outcomes:
measure: Functional Neurophysiological Assessment (FNPA)
timeFrame: Through study completion, an average of 1 year.
measure: Multisegmental Motor Response (MMR)
timeFrame: Through study completion, an average of 1 year.
measure: Transcranial Magnetic Stimulation (TMS)
timeFrame: Through study completion, an average of 1 year.
measure: Aerobic Endurance Test (VO2Peak)
timeFrame: Through study completion, an average of 1 year.
measure: Spinal Cord Independence Measure (SCIM)
timeFrame: Through study completion, an average of 1 year.
measure: The Craig Handicap Assessment & Reporting Technique (CHART)
timeFrame: Through study completion, an average of 1 year.
measure: Beat-by-beat arterial blood pressure
timeFrame: During assessments.
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Frazier Rehabilitation and Neuroscience Institute
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Alexander Ovechkin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gerasimenko Y, Gorodnichev R, Moshonkina T, Sayenko D, Gad P, Reggie Edgerton V. Transcutaneous electrical spinal-cord stimulation in humans. Ann Phys Rehabil Med. 2015 Sep;58(4):225-231. doi: 10.1016/j.rehab.2015.05.003. Epub 2015 Jul 20.