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| ID | Type | Description | Link |
|---|---|---|---|
| R01NS088800 | Other Grant/Funding Number | NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE |
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Botox acts 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 Chronic Migraine (≥15 days per month, with headache lasting 4 hours a day or longer). Gadolinium will be injected with ASIS subdermally (30) or conventional intramuscularly (30) for these 6 muscle groups: Glabella, Frontal, Temporal, Occipital, Paraspinal, and Trapezius. 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 Chronic Migraine, and these particular 6 muscle groups. Case in point, patients with Chronic Migraine presumably have hyperactive Glabella, Frontal, Temporal, Occipital, Paraspinal, and Trapezius muscles, so expectantly will have shortened Gadolinium intramuscularly Persistent %, and somewhat Gadolinium subdermally Persistent % as well due to agitation, thus these Persistent % values in Chronic Migraine patients will not be like those of normal patients, or even the same between these 6 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 particular 6 muscle groups on the same 60 Chronic Migraine adults. Given that there isn't a way to detect Botox in the peripheral blood to document Prolongation of Botox Pharmacokinetically, this Relative Prolongation Ability is our best and only possible way to demonstrate that subdermal bloodless space's ability on Botox. Although valuable, that Relative Prolongation Ability Score from Aim 1 isn't absolutely required to start Aim 2. Hypothetically speaking, if that subdermal bloodless space in patients with e.g., Chronic Migraine 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 reduction in Number of Headache Days from Baseline, and adverse reactions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glabella | Experimental | Glabella Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Frontal | Experimental | Frontal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Temporal | Experimental | Temporal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Occipital | Experimental | Occipital Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Paraspinal | Experimental | Paraspinal 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 conventional intramuscularly (30) in Chronic Migraine adult patients for these 6 muscle groups: Glabella, Frontal, Temporal, Occipital, Paraspinal, and Trapezius. 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 %. This approximation can only work if the variables are minimized to the same population with Chronic Migraine, and these particular 6 muscle groups. The Relative Prolongation Ability Score or total Persistent % subdermally over total Persistent % intramuscularly, in Chronic Migraine patients will not be like those of normal patients, or even the same between these 6 different muscle groups, but valuable indicators to help us modify Botox dosage and duration to inject into "unknown" subdermal bloodless space for Aim 2. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Botox intramuscularly vs. subdermally in Chronic Migraine. | Efficacy of Botox intramuscularly vs. subdermally with ASIS Device at Week 6,12,18, 24, and 30; in terms of Change from baseline in frequency of headache days, and Change from baseline in total cumulative hours of headache on headache days. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Reactions of Botox intramuscularly vs. subdermally in Chronic Migraine. | 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 |
|---|---|---|---|
| 20572569 | Background | Bartleson JD, Cutrer FM. Migraine update. Diagnosis and treatment. Minn Med. 2010 May;93(5):36-41. | |
| 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. |
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| Trapezius | Experimental | Trapezius Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
|
| Change in frequency of headache days | Experimental | Change in frequency of headache days 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. |
|
| Change in hrs of HA on HA days | Experimental | Change in hrs of HA on HA days 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. |
|
| 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 | 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 (onabotulinumtoxinA) intramuscularly at Week 6, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox intramuscularly at Week 12 | Drug | Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 12, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox intramuscularly at Week 18 | Drug | Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 18, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox intramuscularly at Week 24, | Drug | Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 24, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox intramuscularly at Week 30 | Drug | Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 30, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox subdermally at Week 6 | Drug | Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 6, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox subdermally at Week 12 | Drug | Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 12, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox subdermally at Week 18 | Drug | Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 18, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox subdermally at Week 24 | Drug | Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 24, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
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| Efficacy of Botox subdermally at Week 30 | Drug | Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 30, in terms of Change in frequency of headache days, and Change in hrs of HA on HA days. |
|
|
| 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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| 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. |
| 18759544 | Background | Montagna P. Migraine genetics. Expert Rev Neurother. 2008 Sep;8(9):1321-30. doi: 10.1586/14737175.8.9.1321. |
| 20352581 | Background | Robbins MS, Lipton RB. The epidemiology of primary headache disorders. Semin Neurol. 2010 Apr;30(2):107-19. doi: 10.1055/s-0030-1249220. Epub 2010 Mar 29. |
| 19545256 | Background | Levy D, Strassman AM, Burstein R. A critical view on the role of migraine triggers in the genesis of migraine pain. Headache. 2009 Jun;49(6):953-7. doi: 10.1111/j.1526-4610.2009.01444.x. |
| 21649653 | Background | Cousins G, Hijazze S, Van de Laar FA, Fahey T. Diagnostic accuracy of the ID Migraine: a systematic review and meta-analysis. Headache. 2011 Jul-Aug;51(7):1140-8. doi: 10.1111/j.1526-4610.2011.01916.x. Epub 2011 Jun 7. |
| 19539239 | Background | Olesen J, Burstein R, Ashina M, Tfelt-Hansen P. Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol. 2009 Jul;8(7):679-90. doi: 10.1016/S1474-4422(09)70090-0. |
| 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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