Central Nervous System Diseases, Cough, Paralysis, Spinal Cord Diseases, Spinal Cord Injuries, Trauma, Nervous System, Wounds and Injuries
Conditions
Keywords
spinal cord injury, paralysis, cough, cervical spinal cord injury, thoracic spinal cord injury
Brief summary
The purpose of this trial is to determine the efficacy of spinal cord stimulation, using wire leads, to produce an effective cough in patients with spinal cord injuries.
Detailed description
Patients with cervical spinal cord injuries often have paralysis of a major portion of their expiratory muscles - the muscles responsible for coughing - and therefore, lack a normal cough mechanism. Consequently, most of these patients suffer from a markedly reduced ability to clear airway secretions, a factor which contributes to the development of recurrent respiratory tract infections such as pneumonia and bronchitis. Expiratory muscles can be activated by electrical stimulation of the spinal roots to produce a functionally effective cough. The purpose of this trial is to determine if electrical stimulation of the expiratory muscles by wire leads is capable of producing an effective cough on demand. According to the trial researchers, if successful, this technique will prevent the need for frequent patient suctioning - which often requires the constant presence of trained personnel. It will also allow spinal cord injured patients to clear their secretions more readily, thereby reducing the incidence of respiratory complications and associated illness and death. In the trial, researchers will study 16 adults (18-75 years old) with cervical spinal injuries (C8 level or higher), at least 6 months following the date of injury. After an evaluation of medical history, a brief physical examination, and initial testing, participants will have wire leads placed - by a routine, minimally invasive surgical procedure - over the surface of their spinal cords on the lower back to stimulate the expiratory muscles and restore cough.
Interventions
The expiratory muscle stimulator consists of two small electrodes (wire leads) implanted on the surface of the spinal cord on the lower back to stimulate the expiratory muscles and restore cough. These electrodes are connected to an implanted receiver in the abdomen or chest wall. The device is activated through an external antenna connected to an external control box.
PROCEDUREImplantation of device
The expiratory muscle stimulator consists of two wire leads(each with two metal contacts) inserted onto the surface of their spinal cord on the lower back using a needle. The procedure to implant these wire leads is commonly used today for other purposes. This is a minimally invasive surgical technique with minimal risks. The wire leads are connected to an implanted receiver in the abdomen or chest wall. The device is activated through an external antenna connected to an external control box to stimulate the expiratory muscles and restore cough.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
MetroHealth Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Spinal cord injury C8 level or higher * 12 months post-injury (if the American Spinal Injury Association (ASIA) Impairment Scale (AIS) incomplete) or 6 months post-injury (if AIS complete) * Expiratory muscle weakness * Between 18 and 75 years of age * Adequate oxygenation
Exclusion criteria
* Untreated lung, cardiovascular or brain disease * Scoliosis, chest wall deformity, or marked obesity * Unmanaged hypertension (high blood pressure) or hypotension (low blood pressure) * Low oxygenation * Minor infection at the site of implantation requiring antibiotics within the past 3 weeks * Serious infection requiring hospitalization within the past 6 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough. | 52 weeks (1 year) | Peak Expiratory airflow rate is a person's maximum speed of expiration. Peak expiratory flow rate is the maximum flow rate generated during a forceful exhalation, starting from full inspiration. It was measured after release of airway occlusion after peak airway pressure was achieved. |
| Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough | 52 weeks (1 year) | Maximum expiratory pressure is the highest pressure that can be developed during a forceful expiratory effort against an occluded airway. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secretion Management Episodes | 52 weeks (1 year) | This assessment allowed to characterize the severity of secretion management episodes and subjective assessment of the need for secretion management before and after use of the Cough System. Design: Prospective assessment via questionnaire responses Question: How significant were your needs for assistance with managing your airway secretions on a typical day during the past week? 0 None - Unaware of need 1. Mild - Did not interfere with usual daily activities 2. Moderate - Most stop activity during need 3. Marked - Most stop activity for brief period (10-30 min) after need 4. Severe - Most stop activity for prolonged period (\> 30 min) after need, may be accompanied by dizziness, headache and/or pain in upper chest |
| Difficulty Raising Sputum | 52 weeks (1 year) | Survey to assess difficulty raising sputum Objectives: To determine the difficulty raising sputum before and after use of the cough stimulation system (Cough System) Design: Prospective assessment via questionnaire responses Question: How much difficulty have you had with managing your airway secretions? On a scale of 0-4 (0 = None (No secretions), 1 = Mild (Rarely have difficulty), 2 = Moderate (Occasional difficulty) 3 = Marked (Frequent difficulty) and 4=Severe (Usually have great difficulty). |
| Number of Respiratory Tract Infections | 52 weeks (1 year) | Form covers frequency, type, severity, and antibiotic use for respiratory tract infections. The incidence of acute respiratory tract infections, defined by a change in the character, color, or amount of respiratory secretions and requiring antibiotic administration was tracked before and after implantation of the cough system. The occurrence of respiratory tract infections was determined by subject history and corroborated by review of medical records, when available. |
| Life Quality Assessment -Stress Level | 52 weeks (1 year) | Survey will assess the subject's quality of life at home and in social situations, as well as assess specific need for managing secretions. Objectives: Life Quality Assessment before and after use of the cough stimulation system (Cough System) Design: Prospective assessment via questionnaire responses Question: To what extent did managing your airway secretions cause you stress? On a scale of 0-3 (0 = Not at all, 1 = a little, 2 = Quite a bit and 3 = Very much) |
Countries
United States
Participant flow
Recruitment details
Subjects were well informed of the details of the study, with particular interest to risks/benefits, and asked to review the Informed Consent before signing. They were given an opportunity to ask questions. Consent was obtained only after all questions and concerns have been addressed.
Participants by arm
| Arm | Count |
|---|---|
| Clinical Trial: Spinal Cord Stimulation to Restore Cough Procedure/Surgery: Implantation of device; Device: Expiratory Muscle Stimulator
Expiratory muscle stimulator: The expiratory muscle stimulator consists of two small electrodes (wire leads) implanted on the surface of the spinal cord on the lower back to stimulate the expiratory muscles and restore cough. These electrodes are connected to an implanted receiver in the abdomen or chest wall. The device is activated through an external antenna connected to an external control box.
Implantation of device: The expiratory muscle stimulator consists of two wire leads(each with two metal contacts) inserted onto the surface of their spinal cord on the lower back using a needle. The procedure to implant these wire leads is commonly used today for other purposes. This is a minimally invasive surgical technique with minimal risks. The wire leads are connected to an implanted receiver in the abdomen or chest wall. The device is activated through an external antenna connected to an external control box to stimulate the expiratory muscles and restore cough. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Clinical Trial: Spinal Cord Stimulation to Restore Cough |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Pre-Implant - Spontaneous Effort - Airway Pressure | 24.7 cmH2O STANDARD_DEVIATION 12.9 |
| Race/Ethnicity, Customized Caucasian | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough
Maximum expiratory pressure is the highest pressure that can be developed during a forceful expiratory effort against an occluded airway.
Time frame: 52 weeks (1 year)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough | Pre-Implant -Spontaneous Effort | 25 cmH2O | Standard Error 4 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough | Post-Implantation Week #28 | 112 cmH2O | Standard Error 13 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough | Post-Implantation Week #40 | 117 cmH2O | Standard Error 14 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Maximum Airway Pressure to Evaluate Efficacy of Cough | Post-Implantation Week #52 | 118 cmH2O | Standard Error 14 |
Comparison: Each patient was served as their own control (Pre-Implant); comparisons were made at various points in the study (Week #28, #40 and #52).p-value: <0.05ANOVA
Primary
Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough.
Peak Expiratory airflow rate is a person's maximum speed of expiration. Peak expiratory flow rate is the maximum flow rate generated during a forceful exhalation, starting from full inspiration. It was measured after release of airway occlusion after peak airway pressure was achieved.
Time frame: 52 weeks (1 year)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough. | Pre-Implant - Spontaneous Effort | 2.1 L/s | Standard Error 0.4 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough. | Post-Implantation Week #28 | 9.6 L/s | Standard Error 1.2 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough. | Post-Implantation Week #40 | 10.4 L/s | Standard Error 1.3 |
| Peak Expiratory Airflow Rate (L/s) | Measurements of Peak Expiratory Airflow Rate to Evaluate Efficacy of Cough. | Post-Implantation Week #52 | 11.1 L/s | Standard Error 1.6 |
Comparison: Each patient was served as their own control (Pre-Implant); comparisons was made at various points in the study (Week #28, #40 and #52).p-value: <0.05ANOVA
Secondary
Difficulty Raising Sputum
Survey to assess difficulty raising sputum Objectives: To determine the difficulty raising sputum before and after use of the cough stimulation system (Cough System) Design: Prospective assessment via questionnaire responses Question: How much difficulty have you had with managing your airway secretions? On a scale of 0-4 (0 = None (No secretions), 1 = Mild (Rarely have difficulty), 2 = Moderate (Occasional difficulty) 3 = Marked (Frequent difficulty) and 4=Severe (Usually have great difficulty).
Time frame: 52 weeks (1 year)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Difficulty Raising Sputum | Pre-Implantation | 2.64 score on a scale | Standard Error 0.41 |
| Peak Expiratory Airflow Rate (L/s) | Difficulty Raising Sputum | Post-Implantation Week #28 | 0.64 score on a scale | Standard Error 0.24 |
| Peak Expiratory Airflow Rate (L/s) | Difficulty Raising Sputum | Post-Implantation Week #40 | 0.55 score on a scale | Standard Error 0.21 |
| Peak Expiratory Airflow Rate (L/s) | Difficulty Raising Sputum | Post-Implantation Week #52 | 0.36 score on a scale | Standard Error 0.2 |
Comparison: The data prior to implantation (Pre-Implant) were compared with data obtained after implantation (Week #28, #40, #52) of the cough system using a nonparametric analog (Friedman Test) to the standard repeated measures analysis of variance. A p value was calculated. This alpha level was chosen as a correlation for inflated type I error rates because of multiple comparisons. Results are reported as means ± Standard Error.p-value: <0.05nonparametric analog (Freidman Test)
Secondary
Life Quality Assessment -Stress Level
Survey will assess the subject's quality of life at home and in social situations, as well as assess specific need for managing secretions. Objectives: Life Quality Assessment before and after use of the cough stimulation system (Cough System) Design: Prospective assessment via questionnaire responses Question: To what extent did managing your airway secretions cause you stress? On a scale of 0-3 (0 = Not at all, 1 = a little, 2 = Quite a bit and 3 = Very much)
Time frame: 52 weeks (1 year)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Life Quality Assessment -Stress Level | Pre-Implantation | 2.27 score on a scale | Standard Error 0.24 |
| Peak Expiratory Airflow Rate (L/s) | Life Quality Assessment -Stress Level | Post-Implantation Week #28 | 0.18 score on a scale | Standard Error 0.18 |
| Peak Expiratory Airflow Rate (L/s) | Life Quality Assessment -Stress Level | Post-Implantation Week #40 | 0.18 score on a scale | Standard Error 0.18 |
| Peak Expiratory Airflow Rate (L/s) | Life Quality Assessment -Stress Level | Post-Implantation Week #52 | 0.27 score on a scale | Standard Error 0.27 |
Comparison: The data prior to implantation (Pre-Implant) were compared with data obtained after implantation (Week #28, #40, #52) of the cough system using a nonparametric analog (Friedman Test) to the standard repeated measures analysis of variance. A p value was calculated. This alpha level was chosen as a correlation for inflated type I error rates because of multiple comparisons. Results are reported as means ± Standard Error.p-value: <0.05nonparametric analog (Freidman Test)
Secondary
Number of Respiratory Tract Infections
Form covers frequency, type, severity, and antibiotic use for respiratory tract infections. The incidence of acute respiratory tract infections, defined by a change in the character, color, or amount of respiratory secretions and requiring antibiotic administration was tracked before and after implantation of the cough system. The occurrence of respiratory tract infections was determined by subject history and corroborated by review of medical records, when available.
Time frame: 52 weeks (1 year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Number of Respiratory Tract Infections | 1.5 Respiratory tract infections per year | Standard Error 0.6 |
| Number of Respiratory Tract Infections: Post-Implant - After Use of the Cough System (Week #52) | Number of Respiratory Tract Infections | 0.1 Respiratory tract infections per year | Standard Error 0.1 |
Comparison: The data prior to implantation (Pre-Implant) were compared with data obtained after implantation (Week #28 ,#40, #52) of the cough system using a nonparametric analog (Friedman Test) to the standard repeated measures analysis of variance. Paired t test. A p value was calculated. This alpha level was chosen as a correlation for inflated type I error rates because of multiple comparisons. Results are reported as means ± Standard Error.p-value: <0.05nonparametric analog (Freidman Test)
Secondary
Secretion Management Episodes
This assessment allowed to characterize the severity of secretion management episodes and subjective assessment of the need for secretion management before and after use of the Cough System. Design: Prospective assessment via questionnaire responses Question: How significant were your needs for assistance with managing your airway secretions on a typical day during the past week? 0 None - Unaware of need 1. Mild - Did not interfere with usual daily activities 2. Moderate - Most stop activity during need 3. Marked - Most stop activity for brief period (10-30 min) after need 4. Severe - Most stop activity for prolonged period (\> 30 min) after need, may be accompanied by dizziness, headache and/or pain in upper chest
Time frame: 52 weeks (1 year)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peak Expiratory Airflow Rate (L/s) | Secretion Management Episodes | Pre-Implant | 2.73 score on a scale | Standard Error 0.41 |
| Peak Expiratory Airflow Rate (L/s) | Secretion Management Episodes | Post-Implantation Week #28 | 0.45 score on a scale | Standard Error 0.21 |
| Peak Expiratory Airflow Rate (L/s) | Secretion Management Episodes | Post-Implantation Week #40 | 0.55 score on a scale | Standard Error 0.21 |
| Peak Expiratory Airflow Rate (L/s) | Secretion Management Episodes | Post-Implantation Week #52 | 0.45 score on a scale | Standard Error 0.21 |
Comparison: The data prior to implantation (Pre-Implant)) were compared with data obtained after implantation (Week ##28, #40, #52) of the cough system using a nonparametric analog (Friedman Test) to the standard repeated measures analysis of variance. A p value was calculated. This alpha level was chosen as a correlation for inflated type I error rates because of multiple comparisons. Results are reported as means ± Standard Error.p-value: <0.05nonparametric analog (Freidman Test)