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| ID | Type | Description | Link |
|---|---|---|---|
| R44HD081800 | Other Grant/Funding Number | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Biceps Brachii | Experimental | Biceps Brachii (elbow flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Flexor Carpi Radialis | Experimental | Flexor Carpi Radialis (wrist flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Flexor carpi ulnaris | Experimental | Flexor carpi ulnaris (wrist flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Flexor digitorum profundus | Experimental | Flexor digitorum profundus (finger flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Flexor digitorum sublimis | Experimental | Flexor digitorum sublimis (finger flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gadolinium | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Prolongation Ability Score for Gadolinium subdermally injected. | 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. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Botox intramuscularly vs. subdermally in Upper Limb Spasticity. | 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)
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Reactions of Botox intramuscularly vs. subdermally in Upper Limb Spasticity | 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. | 12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Li Nguyen, MD | Contact | (714)-453-7857 | dr.li.nguyen@asis-inc.com | |
| Thanh Phung, MD | Contact | 714-893-1915 | thanhphung@idit-inc.com |
| Name | Affiliation | Role |
|---|---|---|
| Li Nguyen, MD | AUTOMATIC SUBDERMAL INJECTOR SYSTEM INC | Principal Investigator |
| Thanh Phung,, MD | AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Automatic Subdermal Injector System, Inc | Westminster | California | 92683 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23515199 | Background | Lorenc ZP, Kenkel JM, Fagien S, Hirmand H, Nestor MS, Sclafani AP, Sykes JM, Waldorf HA. A review of onabotulinumtoxinA (Botox). Aesthet Surg J. 2013 Mar;33(1 Suppl):9S-12S. doi: 10.1177/1090820X12474629. | |
| 16763467 | Background | Knopp MV, Balzer T, Esser M, Kashanian FK, Paul P, Niendorf HP. Assessment of utilization and pharmacovigilance based on spontaneous adverse event reporting of gadopentetate dimeglumine as a magnetic resonance contrast agent after 45 million administrations and 15 years of clinical use. Invest Radiol. 2006 Jun;41(6):491-9. doi: 10.1097/01.rli.0000209657.16115.42. |
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| Adductor pollicis | Experimental | Adductor pollicis (thumb flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Flexor pollicis longus | Experimental | Flexor pollicis longus (thumb flexors) Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Change from Baseline in Elbow Ashworth | Experimental | Change from Baseline in Elbow Ashworth Scale as Efficacy of Botox intramuscularly at Week 6, Efficacy of Botox intramuscularly at Week 12, Efficacy of Botox intramuscularly at Week 18, Efficacy of Botox intramuscularly at Week 24, and Efficacy of Botox intramuscularly at Week 30 vs.Efficacy of Botox subdermally at Week 6, Efficacy of Botox subdermally at Week 12, Efficacy of Botox subdermally at Week 18, Efficacy of Botox subdermally at Week 24, and Efficacy of Botox subdermally at Week 30. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none)
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| Change from Baseline in Wrist Ashworth | Experimental | Change from Baseline in Wrist Ashworth Scale as Efficacy of Botox intramuscularly at Week 6, Efficacy of Botox intramuscularly at Week 12, Efficacy of Botox intramuscularly at Week 18, Efficacy of Botox intramuscularly at Week 24, and Efficacy of Botox intramuscularly at Week 30 vs.Efficacy of Botox subdermally at Week 6, Efficacy of Botox subdermally at Week 12, Efficacy of Botox subdermally at Week 18, Efficacy of Botox subdermally at Week 24, and Efficacy of Botox subdermally at Week 30.Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none)
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| Change from Baseline in Finger Ashworth | Experimental | Change from Baseline in Finger Ashworth Scale as Efficacy of Botox intramuscularly at Week 6, Efficacy of Botox intramuscularly at Week 12, Efficacy of Botox intramuscularly at Week 18, Efficacy of Botox intramuscularly at Week 24, and Efficacy of Botox intramuscularly at Week 30 vs.Efficacy of Botox subdermally at Week 6, Efficacy of Botox subdermally at Week 12, Efficacy of Botox subdermally at Week 18, Efficacy of Botox subdermally at Week 24, and Efficacy of Botox subdermally at Week 30. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none)
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| Change from Baseline in Thumb Ashworth | Experimental | Change from Baseline in Thumb Ashworth Scale as Efficacy of Botox intramuscularly at Week 6, Efficacy of Botox intramuscularly at Week 12, Efficacy of Botox intramuscularly at Week 18, Efficacy of Botox intramuscularly at Week 24, and Efficacy of Botox intramuscularly at Week 30 vs.Efficacy of Botox subdermally at Week 6, Efficacy of Botox subdermally at Week 12, Efficacy of Botox subdermally at Week 18, Efficacy of Botox subdermally at Week 24, and Efficacy of Botox subdermally at Week 30. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none)
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| Change from Baseline in PGAS | Experimental | Change from Baseline in PGAS as Efficacy of Botox intramuscularly at Week 6, Efficacy of Botox intramuscularly at Week 12, Efficacy of Botox intramuscularly at Week 18, Efficacy of Botox intramuscularly at Week 24, and Efficacy of Botox intramuscularly at Week 30 vs.Efficacy of Botox subdermally at Week 6, Efficacy of Botox subdermally at Week 12, Efficacy of Botox subdermally at Week 18, Efficacy of Botox subdermally at Week 24, and Efficacy of Botox subdermally at Week 30. The Physician Global Assessment Scale or PGAS is a 9 category scale scoring the physician's evaluation of the patients' status compared to baseline, ranging from -4 to +4 (very marked worsening to complete improvement), with 0 indicating no change from baseline and +1 slight improvement. |
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| Adverse Reactions with Facial paresis | Experimental | Facial paresis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30 |
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| Adverse Reactions with Eyelid ptosis | Experimental | Eyelid ptosis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Bronchitis | Experimental | Bronchitis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Neck pain | Experimental | Neck pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Muscle stiffness | Experimental | Musculoskeletal stiffness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Muscular weakness | Experimental | Muscular weakness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Myalgia | Experimental | Myalgia as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Muscle pain | Experimental | Musculoskeletal pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Muscle spasms | Experimental | Muscle spasms as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions Injection site pain | Experimental | Injection site pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Adverse Reactions with Hypertension | Experimental | Hypertension as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
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| Gadolinium | Drug | Gadolinium .1cc/ diluted with .9ccNS subdermally with ASIS Device for 30 patients. Total cumulative Persistent % of Gadolinium subdermally on MRI at 6 hrs, 12 hrs, and 24 hrs. |
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| Gadolinium | Drug | Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI. |
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| Efficacy of Botox intramuscularly at Week 6 | Drug | 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. |
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| Efficacy of Botox intramuscularly at Week 12, | Drug | 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. |
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| Efficacy of Botox intramuscularly at Week 18 | Drug | 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. |
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| Efficacy of Botox intramuscularly at Week 24 | Drug | 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. |
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| Efficacy of Botox intramuscularly at Week 30 | Drug | 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. |
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| Efficacy of Botox subdermally at Week 6 | Drug | 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. |
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| Efficacy of Botox subdermally at Week 12 | Drug | 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. |
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| Efficacy of Botox subdermally at Week 18 | Drug | 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. |
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| Efficacy of Botox subdermally at Week 24 | Drug | 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. |
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| Efficacy of Botox subdermally at Week 30 | Drug | 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. |
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| Adverse Reactions of Botox intramuscularly | Drug | 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. |
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| Adverse Reactions of Botox subdermally | Drug | 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. |
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| 12 months |
| 11991094 | Background | Turner-Stokes L, Ward A. Botulinum toxin in the management of spasticity in adults. Clin Med (Lond). 2002 Mar-Apr;2(2):128-30. doi: 10.7861/clinmedicine.2-2-128. |
| 16541938 | Background | Patrick E, Ada L. The Tardieu Scale differentiates contracture from spasticity whereas the Ashworth Scale is confounded by it. Clin Rehabil. 2006 Feb;20(2):173-82. doi: 10.1191/0269215506cr922oa. |
| 24361062 | Background | Jost WH, Hefter H, Reissig A, Kollewe K, Wissel J. Efficacy and safety of botulinum toxin type A (Dysport) for the treatment of post-stroke arm spasticity: results of the German-Austrian open-label post-marketing surveillance prospective study. J Neurol Sci. 2014 Feb 15;337(1-2):86-90. doi: 10.1016/j.jns.2013.11.022. Epub 2013 Nov 22. |
| 23864518 | Background | Baker JA, Pereira G. The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach. Clin Rehabil. 2013 Dec;27(12):1084-96. doi: 10.1177/0269215513491274. Epub 2013 Jul 17. |
| 23776717 | Background | Ghasemi M, Salari M, Khorvash F, Shaygannejad V. A literature review on the efficacy and safety of botulinum toxin: an injection in post-stroke spasticity. Int J Prev Med. 2013 May;4(Suppl 2):S147-58. |
| ID | Term |
|---|---|
| D005682 | Gadolinium |
| D019786 | Gadolinium DTPA |
| D019274 | Botulinum Toxins, Type A |
| ID | Term |
|---|---|
| D028581 | Lanthanoid Series Elements |
| D008674 | Metals, Rare Earth |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
| D004369 | Pentetic Acid |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D056831 | Coordination Complexes |
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
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