ASIS for Botox in Chronic Migraine

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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ASIS for Botox in Chronic Migraine

Conditions
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Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer.

Intervention / Treatment
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* Drug: Gadolinium
* Drug: Gadolinium
* Drug: Efficacy of Botox intramuscularly at Week 6
* Drug: Efficacy of Botox intramuscularly at Week 12
* Drug: Efficacy of Botox intramuscularly at Week 18
* Drug: Efficacy of Botox intramuscularly at Week 24,
* Drug: Efficacy of Botox intramuscularly at Week 30
* Drug: Efficacy of Botox subdermally at Week 6
* Drug: Efficacy of Botox subdermally at Week 12
* Drug: Efficacy of Botox subdermally at Week 18
* Drug: Efficacy of Botox subdermally at Week 24
* Drug: Efficacy of Botox subdermally at Week 30
* Drug: Adverse Reactions of Botox intramuscularly
* Drug: Adverse Reactions of Botox subdermally


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society for at least 3 months prior to enrollment. Must be able to understand the requirements of the study including maintaining a headache diary, and signing informed consent. If taking migraine preventive, must be on a stable dose of preventive medication for at least 3 months. Exclusion Criteria: Has headache disorders outside IHS-defined chronic migraine definition. Has evidence of underlying pathology contributing to their headaches. Has any pathology of the salivary glands such as sialadenitis (e.g. Sjogren's syndrome, viral or bacterial sialadenitis) or condition or symptom that would alter the content of saliva. Has any medical condition that may increase their risk with exposure to Botox including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function. Has profound atrophy or weakness of muscles in the target areas of injection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glabella<br>Glabella Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Frontal<br>Frontal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Temporal<br>Temporal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Occipital<br>Occipital Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Paraspinal<br>Paraspinal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Trapezius<br>Trapezius Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. | Drug: Gadolinium<br>* 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.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);Drug: Gadolinium<br>* Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.<br>* Other names: Gadolinium Magnevist® (gadopentetate dimeglumine);|
| Experimental: Change in frequency of headache days<br>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. | Drug: Efficacy of Botox intramuscularly at Week 6<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 12<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 18<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 24,<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 30<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 6<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 12<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 18<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 24<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 30<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Change in hrs of HA on HA days<br>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. | Drug: Efficacy of Botox intramuscularly at Week 6<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 12<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 18<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 24,<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox intramuscularly at Week 30<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 6<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 12<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 18<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 24<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Efficacy of Botox subdermally at Week 30<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Facial paresis<br>Facial paresis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Eyelid ptosis<br>Eyelid ptosis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Bronchitis<br>Bronchitis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Neck pain<br>Neck pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Muscle stiffness<br>Musculoskeletal stiffness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Muscular weakness<br>Muscular weakness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Myalgia<br>Myalgia as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Muscle pain<br>Musculoskeletal pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Muscle spasms<br>Muscle spasms as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions Injection site pain<br>Injection site pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|
| Experimental: Adverse Reactions with Hypertension<br>Hypertension as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. | Drug: Adverse Reactions of Botox intramuscularly<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);Drug: Adverse Reactions of Botox subdermally<br>* 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.<br>* Other names: Botox (onabotulinumtoxinA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Migraine, intramuscular injection, Subdermal bloodless space, Subdermal injection, injectable EMG needle, electrical stimulation, MRI with Gadolinium