Upper Limb Spasticity
Conditions
Brief summary
A proof of concept study to evaluate the feasibility of safe and effective treatment of upper limb spasticity using the Cryo-Touch III Device.
Detailed description
Spasticity, common in neurological disorders, is part of the upper motor neuron syndrome displaying increased tone, clonus, spasms, spastic dystonia and co- contractions. The impact of spasticity on the patient varies from a subtle neurological sign to severe spasticity causing pain and contractures. Upper limb spasticity (ULS) is the rapid contraction or shortening of the muscles in the arm causing abnormal muscle movements in the elbow, wrist and fingers. It has been reported that over 1 million Americans with traumatic injury to the brain or spinal cord, stroke, multiple sclerosis and cerebral palsy experience ULS. Tightly clenched fists, twisted wrist and elbow joints, and fixed arms in flexed positions result in extreme discomfort, pain and spasm. A nonsurgical, minimally invasive, effective approach to pain associated with ULS is desirable. Myoscience, Inc. (Redwood City, CA) has developed a pain management device - the Cryo-Touch III - for a novel, minimally invasive procedure using focused cold therapy to target sensory nerve tissue and offer long-lasting pain relief through cryoanalgesia. The device operates on the well-established cryobiology principle that localized exposure to controlled, moderately low temperature conditions can alter tissue function. The therapy treats nerves via a probe in the form of an assembly of small diameter needles, creating a highly localized, low temperature treatment zone around the probe. This focused cold therapy creates a conduction block that prevents nerve signaling. Prior studies of the Cryo-Touch, Cryo-Touch II, Cryo-Touch III (a.k.a. PCP 1.0) devices have provided preliminary evidence of effectiveness on motor nerves and have been shown to be safe with no serious device-related adverse events.
Interventions
DEVICETreatment with Cryo-Touch III device
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years of age and older. 2. Trial participants must have a confirmed diagnosis that results in spasticity involving muscle innervated by the musculocutaneous nerve (MCN). 3. Any medications must be maintained on a stable schedule for at least two weeks prior to treatment. No washout period is allowed. 4. Must have an average score on the Modified Ashworth Scale for Spasticity of ≥ 2 over the last 30 days in the elbow. 5. Subject, in the Investigator's opinion, will not be exposed to unacceptable risk by participation.
Exclusion criteria
1. Previous surgical intervention that altered the target neural anatomy of the upper limb. 2. Any injection (neurolytic, sclerosing, anesthetic, etc.) to the upper limb within the last 4 months. 3. Current enrollment in an investigational drug or device study that specifically targets spasticity management. 4. Allergy or intolerance to local anesthesia. 5. Any local skin condition at the treatment site that in the investigator's opinion would adversely affect treatment or outcomes. 6. Any chronic medication use (prescription, over-the-counter, etc.) that in the investigator's opinion would affect study participation or subject safety. 7. Diagnosis of cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, Raynaud's disease, open and/or infected wounds. 8. Diagnosis of progressive neurologic diseases such as ALS. 9. For any reason, in the opinion of the investigator, the subject may not be a suitable candidate for study participation (i.e., history of noncompliance, drug dependency, any related upper limb injury, etc.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7 | Baseline to: post-treatment (Day 0), Day 7, Day 30 | The Modified Ashworth Scale (MAS) is 6-point scale designed to assess muscle tone and spasticity through the flexion or extension of a joint. Muscle response is graded on a scale from 0 (no increase in muscle tone) to 4 (affected parts rigid in flexion or extension). This includes a 1+ rating, which further distinguishes the types of increase in muscle tone from those described by a 1 or 2 rating. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Baseline to: post-treatment (Day 0), Day 7, Day 30 | The Penn Spasm Score, which is a patient reported score, consists of two sub-scales: the spasm frequency score and the spasm severity scale3. The Penn spasm frequency is assessed on a 5-point scale from 0 (no spasms) to 4 (spasms occurring more than ten times per hour). The spasm severity scale consists of three ratings, which are 1 (mild), 2 (moderate) and 3 (severe). |
| Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only) | Baseline to: post-treatment (Day 0), Day 7, Day 30 | The Fugl-Meyer Scale is an assessment consisting of 33 movements, each rated as 0 (cannot perform), 1 (can partially perform) or 2 (can perform fully). A Subject's score is the sum of their ratings on each of these items, where the maximum (best) score is a 66. |
| Improvement in Spasticity as Measured by the Tardieu Scale | Baseline to: post-treatment (Day 0), Day 7, Day 30 | The Tardieu Scale uses the application of stretch at several velocities to quantify muscle response and assess muscle spasticity. Two specified velocities were assessed (V1 and V2). For each stretch, quality of muscle reaction (X) is recorded on a 6-point scale from 0 (no resistance throughout passive movement) to 5 (immovable joint). |
| Improvement in Pain as Assessed by Visual Analog Scale (VAS) | Baseline to: Post-treatment (Day 0), Day 7, Day 30 | Visual Analog Scale assesses pain on a 0-10 point range. 0= no pain and 10 is the worst pain imaginable. Higher score is associated with a worse outcome. |
| Duration of Treatment Effect | Day 7, Day 30, Day 56, Day 84, Day 112 | Subjects were asked to report the duration of treatment effect at Day 7,Day 30, and Day 56. Subjects could designate their results as effect no effect or no longer effective. Subjects reporting effect at Day 56 were followed to Day 84; those with effect at Day 84 continued to be followed to Day 112. |
| Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score | baseline to: post-treatment (Day 0), Day 7, Day 30 | The NRS is an 11-point scale from 0 to 10, where lower scores represent less spasticity. |
Countries
United States
Participant flow
Recruitment details
Enrollment for the study was initiated April 22, 2013 and was completed June 28, 2013 at two investigational sites.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With the Cryo-Touch III Device Treatment with Cryo-Touch III device | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Treatment With the Cryo-Touch III Device |
|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 15.6 |
| Primary Diagnosis Other: Spinal Cord Injury | 1 Participants |
| Primary Diagnosis Stroke | 16 Participants |
| Primary Diagnosis Traumatic Brain Injury | 2 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 1 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7
The Modified Ashworth Scale (MAS) is 6-point scale designed to assess muscle tone and spasticity through the flexion or extension of a joint. Muscle response is graded on a scale from 0 (no increase in muscle tone) to 4 (affected parts rigid in flexion or extension). This includes a 1+ rating, which further distinguishes the types of increase in muscle tone from those described by a 1 or 2 rating.
Time frame: Baseline to: post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7 | Average MAS score Baseline | 3.3 average MAS Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7 | Average MAS score post-treatment | 1.3 average MAS Score, absolute | Standard Deviation 0.8 |
| Treatment With the Cryo-Touch III Device | Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7 | Average MAS Score Day 7 | 1.7 average MAS Score, absolute | Standard Deviation 0.9 |
| Treatment With the Cryo-Touch III Device | Decrease in Pain and Symptoms Caused by Hypertonia in the Upper Arm as Measured by an Improvement of 1 Point or Greater on the Modified Ashworth Scale (MAS) at Day 7 | Average MAS score Day 30 | 1.5 average MAS Score, absolute | Standard Deviation 0.9 |
Secondary
Duration of Treatment Effect
Subjects were asked to report the duration of treatment effect at Day 7,Day 30, and Day 56. Subjects could designate their results as effect no effect or no longer effective. Subjects reporting effect at Day 56 were followed to Day 84; those with effect at Day 84 continued to be followed to Day 112.
Time frame: Day 7, Day 30, Day 56, Day 84, Day 112
Population: Subjects reporting effect at Day 56 were followed to Day 84; those with effect at Day 84 continued to be followed to Day 112.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Duration of Treatment Effect | Day 7 | 15 Participants |
| Treatment With the Cryo-Touch III Device | Duration of Treatment Effect | Day 30 | 17 Participants |
| Treatment With the Cryo-Touch III Device | Duration of Treatment Effect | Day 56 | 10 Participants |
| Treatment With the Cryo-Touch III Device | Duration of Treatment Effect | Day 84 | 7 Participants |
| Treatment With the Cryo-Touch III Device | Duration of Treatment Effect | Day 112 | 6 Participants |
Secondary
Improvement in Pain as Assessed by Visual Analog Scale (VAS)
Visual Analog Scale assesses pain on a 0-10 point range. 0= no pain and 10 is the worst pain imaginable. Higher score is associated with a worse outcome.
Time frame: Baseline to: Post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Improvement in Pain as Assessed by Visual Analog Scale (VAS) | Average VAS score baseline | 1.0 average VAS Score, absolute | Standard Deviation 2 |
| Treatment With the Cryo-Touch III Device | Improvement in Pain as Assessed by Visual Analog Scale (VAS) | Average VAS score Post-treatment | 0.4 average VAS Score, absolute | Standard Deviation 0.8 |
| Treatment With the Cryo-Touch III Device | Improvement in Pain as Assessed by Visual Analog Scale (VAS) | Average VAS score Day 7 | 0.6 average VAS Score, absolute | Standard Deviation 1.4 |
| Treatment With the Cryo-Touch III Device | Improvement in Pain as Assessed by Visual Analog Scale (VAS) | Average VAS score Day 30 | 1.2 average VAS Score, absolute | Standard Deviation 2.1 |
Secondary
Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score
The Penn Spasm Score, which is a patient reported score, consists of two sub-scales: the spasm frequency score and the spasm severity scale3. The Penn spasm frequency is assessed on a 5-point scale from 0 (no spasms) to 4 (spasms occurring more than ten times per hour). The spasm severity scale consists of three ratings, which are 1 (mild), 2 (moderate) and 3 (severe).
Time frame: Baseline to: post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Frequency Score baseline | 1.3 Average Penn Spasm Score, absolute | Standard Deviation 1.5 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Frequency Score Post-treatment | 0.7 Average Penn Spasm Score, absolute | Standard Deviation 1.1 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Frequency Score Day 7 | 0.7 Average Penn Spasm Score, absolute | Standard Deviation 1.1 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Frequency Score Day 30 | 0.7 Average Penn Spasm Score, absolute | Standard Deviation 1 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Severity Score Baseline | 2.4 Average Penn Spasm Score, absolute | Standard Deviation 0.5 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Severity Score Post-treatment | 1.6 Average Penn Spasm Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Severity Score Day 7 | 1.8 Average Penn Spasm Score, absolute | Standard Deviation 0.8 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasm Frequency and Severity as Measured by the Penn Spasm Score | Average Penn Severity Score Day 30 | 2.1 Average Penn Spasm Score, absolute | Standard Deviation 0.7 |
Secondary
Improvement in Spasticity as Measured by the Tardieu Scale
The Tardieu Scale uses the application of stretch at several velocities to quantify muscle response and assess muscle spasticity. Two specified velocities were assessed (V1 and V2). For each stretch, quality of muscle reaction (X) is recorded on a 6-point scale from 0 (no resistance throughout passive movement) to 5 (immovable joint).
Time frame: Baseline to: post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V1 Baseline | 1.7 average X Score, absolute | Standard Deviation 0.4 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X score V1 at post-treatment | 1.1 average X Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V1 at Day 7 | 1.2 average X Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V1 at Day 30 | 0.8 average X Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V2 at Baseline | 1.9 average X Score, absolute | Standard Deviation 0.3 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X score V2 post-treatment | 1.4 average X Score, absolute | Standard Deviation 0.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V2 at Day 7 | 1.5 average X Score, absolute | Standard Deviation 0.5 |
| Treatment With the Cryo-Touch III Device | Improvement in Spasticity as Measured by the Tardieu Scale | Average X Score V2 at Day 30 | 1.3 average X Score, absolute | Standard Deviation 0.7 |
Secondary
Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only)
The Fugl-Meyer Scale is an assessment consisting of 33 movements, each rated as 0 (cannot perform), 1 (can partially perform) or 2 (can perform fully). A Subject's score is the sum of their ratings on each of these items, where the maximum (best) score is a 66.
Time frame: Baseline to: post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only) | Average Fugl-Meyer Sum Score Baseline | 24.5 average Fugl-Meyer Sum Score, absolute | Standard Deviation 17.9 |
| Treatment With the Cryo-Touch III Device | Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only) | Average Fugl-Meyer Sum Score post-treatment | 27.3 average Fugl-Meyer Sum Score, absolute | Standard Deviation 17.1 |
| Treatment With the Cryo-Touch III Device | Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only) | Average Fugl-Meyer Sum Score Day 7 | 24.6 average Fugl-Meyer Sum Score, absolute | Standard Deviation 18.7 |
| Treatment With the Cryo-Touch III Device | Improvement in Upper Extremity Motor Recovery as Measured by the Fugl-Meyer Scale (Post Stroke Subjects Only) | Average Fugl-Meyer Sum Score Day 30 | 22.3 average Fugl-Meyer Sum Score, absolute | Standard Deviation 19.9 |
Secondary
Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score
The NRS is an 11-point scale from 0 to 10, where lower scores represent less spasticity.
Time frame: baseline to: post-treatment (Day 0), Day 7, Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With the Cryo-Touch III Device | Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score | Average NRS score Day 7 | 3.5 average NRS score, absolute | Standard Deviation 1.6 |
| Treatment With the Cryo-Touch III Device | Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score | average NRS Score baseline | 6.7 average NRS score, absolute | Standard Deviation 2 |
| Treatment With the Cryo-Touch III Device | Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score | Average NRS score post-treatment | 2.7 average NRS score, absolute | Standard Deviation 1.5 |
| Treatment With the Cryo-Touch III Device | Subject Assessed Change in Mean Spasticity Numerical Rating Scale (NRS) Score | Average NRS score Day 30 | 4.2 average NRS score, absolute | Standard Deviation 1.8 |