Carpal Tunnel Syndrome
Conditions
Brief summary
This study will be a prospective double blind controlled randomized trial of ten patients diagnosed with Carpal Tunnel Syndrome (CTS). The study will be completed at offices of medical practices in Arizona. Patients who meet inclusion criteria will be randomly distributed into two groups: a BOTOX® (onabotulinumtoxin A) injection group and a Normal Saline Injection (NS) (Placebo group). Each group will consist of five randomly assigned individuals.
Detailed description
This is a pilot study, to assist with determining appropriate BOTOX® (onabotulinumtoxin A) dosing and injection locations in patients suffering from CTS. Outcome measures will be obtained at follow-up at 6, 12, and 18 weeks post BOTOX® (onabotulinumtoxin A) injection and post saline injection using the same scales and instruments at baseline, namely Levine scale, JAMAR pinch dynamometer, EDX/NCS and NMUS. These measurements will be used to identify the effectiveness of BOTOX® (onabotulinumtoxin A) in decreasing thenar muscle strength, appropriate BOTOX® (onabotulinumtoxin A) injection dosing, and ability to decrease the inflammation, median nerve dysfunction, edema, symptoms of pain, numbness, and tingling often with associated with CTS.
Interventions
DRUGBotulinum Toxin Type A
40 units of BOTOX® (onabotulinumtoxin A) divided into two injection sites of 20 units each
DRUGPlacebo
Placebo (Normal Saline) divided into 2 injections of .4cc each
Sponsors
Allergan
Benjamin Sucher
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient history: evaluated using the Levine Scale for CTS, a self-administered questionnaire which assesses the function and severity of CTS. * Physical Exam: including use of JAMAR pinch dynamometer to quantify initial baseline strength and confirm decreased pinch strength post injection to verify effective BOTOX® (onabotulinumtoxin A) injection. * Electrodiagnostics (EDX): The following criteria would establish CTS through EDX namely baseline electromyogram (EMG) and nerve conduction studies (NCS): a) median nerve distal motor latency (DML) \>4.3ms or \>0.9ms above the ulnar nerve DML b) median distal sensory latency (DSL) to D-1 \>2.9ms or \>0.4ms above radial nerve D-1 DSL. c) median D-2 DSL \>3.7ms or \>0.4ms above ulnar nerve D-5 DSL (5). d) median mixed nerve palm-to-wrist latency (at 8cm) \>2.2ms or \>.3ms above ulnar mixed nerve palm-to-wrist latency (at 8cm). * Imaging & Measurements (NMUS): Carpal tunnel images will be obtained in a transverse plane in both a neutral relaxed position at the level of the pisiform and longitudinally during neutral and Dynamic Stress Testing (DST) by a A Sonosite M-Turbo 6-13 MHz ultrasound system or another similar system (+ 2% accuracy). Measurements: Transverse images of the CT will measure the median nerve cross sectional area (CSA) at the level of the pisiform bone. CSA measurements greater than 11 mm2 are indicative of CTS. Borderline CSA measurements would require wrist forearm ratio (WFR) measurements to be a WFR \> 1.5. Patients will need to have a CSA \>11mm2, (or WFR \>1.5) and show median nerve compression during DST of at least 30% to be included.
Exclusion criteria
* Patients with prior carpal tunnel surgery, prior history of BOTOX® (onabotulinumtoxin A) injection * Steroid injection two months prior or three months after BOTOX® (onabotulinumtoxin A) CTS injection, median nerve denervation on needle EMG * Major limb trauma or surgery, dysphagia * Neuromuscular junction disorder (ie: Myasthenia gravis or Lambert-Eaton syndrome) * Currently pregnant or breast feeding * Patients with severe CTS identified by Levine scale \>4, electrodiagnostics, and/or unable to meet the inclusion criteria as identified above would be excluded as participants in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Baseline-Week 18 | Patients with Levine score \< 4 were included in the study. The score for this assessment can range from 11-55. |
| Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Baseline-Week 18 | Patients with Levine score of \< 4 were included in the study. The score for this assessment can range from 8-40 |
| Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Baseline to Week 18 | Neuromuscular ultrasound measures nerve compression (swelling) by cross sectional area of median nerve, in format % change from baseline. |
| Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Baseline, week 6, week 12, and week 18. | Latency is the interval between the stimulation of a muscle and the observed response, measuring conduction speed in milliseconds compared to baseline |
| Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Baseline to Week 18 | Latency is the interval between the stimulation of a muscle and the observed response measuring nerve conduction speed in milliseconds. |
| Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Baseline-Week 18 | Mean value of one finger and two finger opposition pinch between 1st and 5th and 1st with 4th and 5th phalanges. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin Type A (Onabot) A prospective, randomized, double blind pilot study of patients with bilateral mild to moderate CTS, diagnosed by nerve conduction studies (NCS) and NMUS (with crosssectional area measurements; and percentage of nerve compression measured during mechanical stress testing). For 5 out of 10 subjects, non-dominant hands were injected under ultrasound guidance with 40 units of Onabot (0.4cc) divided equally into the abductor pollicis brevis and opponens pollicis muscles. Participants were evaluated with NMUS, NCS, Levine Scale (symptom severity and functional status), and Jamar dynamometer at baseline, 6, 12, and 18 weeks. | 5 |
| Placebo A prospective, randomized, double blind pilot study of 10 patients with bilateral mild to moderate CTS, diagnosed by nerve conduction studies (NCS) and NMUS (with crosssectional area measurements; and percentage of nerve compression measured during mechanical stress testing). Non-dominant hands were injected under ultrasound guidance with 40 units of 40 units of normal saline (0.4cc) divided equally into the abductor pollicis brevis and opponens pollicis muscles. Participants were evaluated with NMUS, NCS, Levine Scale (symptom severity and functional status), and Jamar dynamometer at baseline, 6, 12, and 18 weeks. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Placebo | Botulinum Toxin Type A (Onabot) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Continuous | 52.3 years STANDARD_DEVIATION 20.3 | 60.4 years STANDARD_DEVIATION 17.9 | 56.35 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18.
Latency is the interval between the stimulation of a muscle and the observed response, measuring conduction speed in milliseconds compared to baseline
Time frame: Baseline, week 6, week 12, and week 18.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -0.1 milliseconds | Standard Deviation 0.4 |
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | -0.3 milliseconds | Standard Deviation 0.3 |
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -0.3 milliseconds | Standard Deviation 0.3 |
| Placebo | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -0.1 milliseconds | Standard Deviation 0.1 |
| Placebo | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | 0.0 milliseconds | Standard Deviation 0.1 |
| Placebo | Change From Baseline Electrodiagnostics Distal Sensory Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -0.1 milliseconds | Standard Deviation 0.3 |
Primary
Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18.
Latency is the interval between the stimulation of a muscle and the observed response measuring nerve conduction speed in milliseconds.
Time frame: Baseline to Week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -0.2 milliseconds | Standard Deviation 0.3 |
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | -0.4 milliseconds | Standard Deviation 0.5 |
| Botulinum Toxin Type A | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -0.6 milliseconds | Standard Deviation 0.5 |
| Placebo | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -0.1 milliseconds | Standard Deviation 0.1 |
| Placebo | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | -0.1 milliseconds | Standard Deviation 0.2 |
| Placebo | Change From Baseline Electrodiagnostics Motor Median Nerve Latency at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -0.1 milliseconds | Standard Deviation 0.3 |
Primary
Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18.
Neuromuscular ultrasound measures nerve compression (swelling) by cross sectional area of median nerve, in format % change from baseline.
Time frame: Baseline to Week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -13.0 % change | Standard Deviation 15.3 |
| Botulinum Toxin Type A | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | -15.9 % change | Standard Deviation 19.5 |
| Botulinum Toxin Type A | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -12.2 % change | Standard Deviation 17.8 |
| Placebo | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 2-Week 6 | -20.2 % change | Standard Deviation 18.8 |
| Placebo | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 3-Week 12 | -13.3 % change | Standard Deviation 9.4 |
| Placebo | Change From Baseline in Median Nerve Compression on Neuromuscular Ultrasound at Week 6, Week 12, and Week 18. | Visit 4-Week 18 | -4.7 % change | Standard Deviation 14 |
Primary
Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18.
Mean value of one finger and two finger opposition pinch between 1st and 5th and 1st with 4th and 5th phalanges.
Time frame: Baseline-Week 18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 3-Week 12 | 1.4 Pounds of Force (LBF) | Standard Deviation 0.5 |
| Botulinum Toxin Type A | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 2-Week 6 | 1.1 Pounds of Force (LBF) | Standard Deviation 1.2 |
| Botulinum Toxin Type A | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 4-Week 18 | 1.4 Pounds of Force (LBF) | Standard Deviation 0.5 |
| Placebo | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 3-Week 12 | -0.1 Pounds of Force (LBF) | Standard Deviation 1.7 |
| Placebo | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 2-Week 6 | 0.5 Pounds of Force (LBF) | Standard Deviation 1.2 |
| Placebo | Change From Baseline Jamar Pinch (Unrelated Dominant Hand - Mean Value of All Repetitions/Positions) at Weeks 6, 12,18. | Visit 4-Week 18 | 0.4 Pounds of Force (LBF) | Standard Deviation 1.2 |
Primary
Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18.
Patients with Levine score of \< 4 were included in the study. The score for this assessment can range from 8-40
Time frame: Baseline-Week 18
Population: Levine functional severity scale is a measure of mean of median value calculated for both Onabot and Placebo groups based on patient answered questions. This scale ranges from 1 (no symptoms) to 5 (severe symptoms). The function severity scale indicate interference of the symptoms on activities of daily living. Mean values reported for each group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 2-Week 6 | -1.0 Scores on a scale | Standard Deviation 9.3 |
| Botulinum Toxin Type A | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 3-Week 12 | -3.8 Scores on a scale | Standard Deviation 4.8 |
| Botulinum Toxin Type A | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 4-Week 18 | -4.0 Scores on a scale | Standard Deviation 8.6 |
| Placebo | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 2-Week 6 | -4.4 Scores on a scale | Standard Deviation 11.9 |
| Placebo | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 3-Week 12 | -9.6 Scores on a scale | Standard Deviation 9.3 |
| Placebo | Change From Baseline Levine Function Severity Scale Status at Weeks 6, 12,18. | Visit 4-Week 18 | -12.8 Scores on a scale | Standard Deviation 6.1 |
Primary
Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18.
Patients with Levine score \< 4 were included in the study. The score for this assessment can range from 11-55.
Time frame: Baseline-Week 18
Population: Levine symptom severity scale is a measure of mean of median value calculated for both Onabot and Placebo groups based on patient answered questions. It ranges from 1 (no symptoms) to 5 (severe symptoms). This scale indicate how severe the CTS symptoms feel to the patient. Mean values (std deviation) are reported both Onabot and Placebo groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin Type A | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 2-Week 6 | 0.4 Scores on a scale | Standard Deviation 6.8 |
| Botulinum Toxin Type A | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 3-Week 12 | -4.2 Scores on a scale | Standard Deviation 5.1 |
| Botulinum Toxin Type A | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 4-Week 18 | -5.4 Scores on a scale | Standard Deviation 8.7 |
| Placebo | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 2-Week 6 | -3.2 Scores on a scale | Standard Deviation 6.8 |
| Placebo | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 3-Week 12 | -9.4 Scores on a scale | Standard Deviation 8.3 |
| Placebo | Change From Baseline Levine Symptom Severity Scale Status at Weeks 6, 12,18. | Visit 4-Week 18 | -6.8 Scores on a scale | Standard Deviation 6.8 |