Clinical trial NCT02074163: ASIS for Botox in Chronic Migraine
Official title: ASIS for Botox in Chronic Migraine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer.
Keywords: Subdermal bloodless space
Subdermal injection
injectable EMG needle
electrical stimulation
MRI with Gadolinium
Chronic Migraine
intramuscular injection
Lead sponsor: ASIS Corporation
Sponsor class: INDUSTRY
First posted: 2014-02-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Relative Prolongation Ability Score for Gadolinium subdermally injected.
timeFrame: 12 months
Secondary outcomes:
measure: Efficacy of Botox intramuscularly vs. subdermally in Chronic Migraine.
timeFrame: 12 months
Other outcomes:
measure: Adverse Reactions of Botox intramuscularly vs. subdermally in Chronic Migraine.
timeFrame: 12 months
Locations:
city: Westminster
country: United States
facility: Automatic Subdermal Injector System, Inc
state: California
Study officials:
affiliation: AUTOMATIC SUBDERMAL INJECTOR SYSTEM INC
name: Li Nguyen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC
name: Thanh Phung, MD
role: PRINCIPAL_INVESTIGATOR
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