Increased Muscle Tone in Elbow, Wrist, Finger, and Thumb Flexors., Upper Limb Spasticity Unilaterally in Adults With History of Stroke
Conditions
Keywords
Subdermal bloodless space, Subdermal injection, injectable EMG needle, electrical stimulation, MRI with Gadolinium, Upper Limb Spasticity, intramuscular injection
Brief summary
Botox act on nerve endings, yet there are no nerve endings inside the muscle, where they are typically injected. All nerves terminate on the fascia, where ASIS device can precisely deliver Botox by creating that subdermal bloodless space, between the skin and muscle. Thus enhancing and prolonging Botox's efficacy, at the same time prevent it's unnecessary adverse reactions and distant spread, especially since Botox has no reason to travel to the rest of the body any way.
Detailed description
Aim 1 over 6 months will demonstrate ASIS device's consistent performance on 60 adult subjects with Upper limb Spasticity. Gadolinium will be injected with ASIS subdermally (30) or conventional intramuscularly (30) for these 7 muscle groups: Biceps Brachii, Flexor Carpi Radialis, Flexor Carpi Ulnaris, Flexor Digitorum Profundus, Flexor Digitorum Sublimis, Adductor Pollicis, and Flexor Pollicis Longus. An MRI will be taken promptly after Gadolinium injection, as starting reference, to which subsequent MRI taken at 6 hrs, 12 hrs, and 24 hrs later will be compared for Persistent %. Since there isn't a way to measure level of Gadolinium within it, or any other (e.g. Botox) for that matter, at least the Prolongation of Gadolinium may be approximated by the greater or longer Persistent % on MRI. However, this approximation can only work if the variables are minimized to the same population with Upper limb Spasticity, and these particular 7 muscle groups. Case in point, patients with Upper limb Spasticity presumably have hyperactivity in these 7 muscle groups, so expectantly will have shortened Gadolinium intramuscularly Persistent %, and somewhat reduced Gadolinium subdermally Persistent % as well due to agitation, thus these Persistent % values in Upper limb Spasticity patients will not be like those of normal patients, or even the same between these 7 different muscle groups. Therefore, the Relative Prolongation Ability Score or total Persistent % subdermally over total Persistent % intramuscularly, will be specific and valuable indicators to help us modify the Botox dosage and duration to inject into that unknown subdermal bloodless space for Aim 2. Aim 2 over 12 months, using Botox, instead of Gadolinium, to demonstrate the advantages of ASIS device subdermally over intramuscularly, for the same 60 adult subjects with Upper limb Spasticity, on these particular 7 muscle groups: Biceps Brachii, Flexor Carpi Radialis, Flexor Carpi Ulnaris, Flexor Digitorum Profundus, Flexor Digitorum Sublimis, Adductor Pollicis, and Flexor Pollicis Longus. Hypothetically speaking, if that subdermal bloodless space in patients with e.g., Upper limb Spasticity somehow failed to show prolongation of half-life for Gadolinium in Aim 1, we can still proceed with primary interest being therapeutic comparison for Botox in Aim 2, in terms of improvement on the Physician Global Assessment Scale and Ashworth score (force required to move an extremity around a joint), at 6,12,18,24, and 30 weeks, and reduction in adverse reactions.
Interventions
DRUGGadolinium
Gadolinium .1cc/ diluted with .9ccNS intramuscularly with ASIS Device for 30 patients. Total cumulative Persistent % of Gadolinium intramuscularly on MRI at 6 hrs, 12 hrs, and 24 hrs.
Efficacy of Botox intramuscularly at Week 6, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
DRUGEfficacy of Botox intramuscularly at Week 12,
Efficacy of Botox intramuscularly at Week 12, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox intramuscularly at Week 18, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox intramuscularly at Week 24, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox intramuscularly at Week 30, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox subdermally at Week 6, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox subdermally at Week 12, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox subdermally at Week 18, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox subdermally at Week 24, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Efficacy of Botox subdermally at Week 30, in terms of Change from Baseline in PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Elbow Ashworth, Change from Baseline in Wrist Ashworth, Change from Baseline in Finger Ashworth, and Change from Baseline in Thumb Ashworth.
Adverse Reactions of Botox (onabotulinumtoxinA) intramuscularly at Week 30, in number of Headache Migraine, Facial paresis, Eyelid ptosis, Bronchitis, Neck pain Musculoskeletal stiffness, Muscular weakness Myalgia, Musculoskeletal pain, Muscle spasms, Injection site pain, and Hypertension.
Adverse Reactions of Botox (onabotulinumtoxinA) subdermally at Week 30, in number of Headache Migraine, Facial paresis, Eyelid ptosis, Bronchitis, Neck pain Musculoskeletal stiffness, Muscular weakness Myalgia, Musculoskeletal pain, Muscle spasms, Injection site pain, and Hypertension.
Sponsors
li nguyen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults with history of stroke that resulted in a unilateral, upper-limb focal spasticity * Wrist flexor tone of more than 2 and finger flexor tone of more than 2 as measured by the Ashworth Scale * Ability to understand and follow verbal directions * At least 1 functional disability item (hygiene, dressing, pain, or limb posture) with a rating of more than 2 on the Disability Assessment Scale (DAS) * At least 1 functional task score at Day 0 that met the following criteria: nail filing less than 6, hand cleaning less than 6, holding a water bottle less than 4, brushing teeth less than 4, holding fruit (small, medium, or large equals no.
Exclusion criteria
* Stroke within 6 months of the study enrollment visit * Females who are pregnant, nursing, or planning a pregnancy during the study period or who are not using a reliable means of contraception * Previous or current Botox therapy of any type in the study limb * Any medical condition that may put the patient at increased risk with Botox exposure or any other disorder that might have interfered with neuromuscular function * Presence of fixed contracture of the study limb * Limited use of the wrist and fingers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Prolongation Ability Score for Gadolinium subdermally injected. | 6 months | Gadolinium will be injected with ASIS subdermally (30) or intramuscularly (30) in Upper Limb Spasticity adult patients for these 7 muscle groups: Biceps Brachii, Flexor Carpi Radialis, Flexor Carpi Ulnaris, Flexor Digitorum Profundus, Flexor Digitorum Sublimis, Adductor Pollicis, and Flexor Pollicis Longus. MRI will be taken promptly after, as starting reference, to which subsequent MRI at 6 hrs, 12 hrs, and 24 hrs later will be compared for Persistent %. This approximation can only work if the variables are minimized to the same population with Upper Limb Spasticity, and these particular 7 muscle groups. The Relative Prolongation Ability Score or total Persistent % subdermally over total Persistent % intramuscularly, in Upper Limb Spasticity patients will not be same as normal patients, or even between these 7 different muscle groups, but valuable indicators to help us modify Botox dosage and duration to inject into unknown subdermal bloodless space for Aim 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Botox intramuscularly vs. subdermally in Upper Limb Spasticity. | 12 months | Efficacy of Botox intramuscularly vs. subdermally with ASIS Device at Week 6,12,18, 24, and 30; in terms of improvement on the Physician Global Assessment Scale (-4=very marked worsening to +4=very marked improvement). Also in terms of improvement, or Median Change from Baseline in Flexor Tone on Ashworth Scale, for Elbow, Wrist, Finger, and Thumb. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none) 1. = Slight increase in muscle tone, giving a 'catch' when the limb was flexed or extended (mild) 2. = More marked increase in muscle tone but affected limb is easily flexed (moderate) 3. = Considerable increase in muscle tone - passive movement difficult (severe) 4. = Limb rigid in flexion or extension (very severe). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Reactions of Botox intramuscularly vs. subdermally in Upper Limb Spasticity | 12 months | Adverse Reactions of Botox intramuscularly vs. subdermally: Headache Migraine, Facial paresis, Eyelid ptosis, Bronchitis, Neck pain Musculoskeletal stiffness, Muscular weakness Myalgia, Musculoskeletal pain, Muscle spasms, Injection site pain, and Hypertension. |
Countries
United States
Contacts
Primary ContactLi Nguyen, MD
Backup ContactThanh Phung, MD
Outcome results
None listed