ASIS for Botox in Chronic Migraine (ASISinCM)

ASIS

Status and phase: Unknown; Phase 2; Phase 1

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

Treatments: Drug: Gadolinium; Drug: Efficacy of Botox subdermally at Week 6; Drug: Efficacy of Botox subdermally at Week 12; Drug: Efficacy of Botox intramuscularly at Week 24,; Drug: Efficacy of Botox intramuscularly at Week 6; Drug: Efficacy of Botox intramuscularly at Week 12; Drug: Efficacy of Botox subdermally at Week 24; Drug: Efficacy of Botox subdermally at Week 30; Drug: Efficacy of Botox intramuscularly at Week 30; Drug: Adverse Reactions of Botox intramuscularly; Drug: Efficacy of Botox subdermally at Week 18; Drug: Efficacy of Botox intramuscularly at Week 18; Drug: Adverse Reactions of Botox subdermally

Study type: Interventional

Funder types: Industry

Identifiers

NCT02074163

NCTNS088800

R01NS088800 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 19 patient groups

Glabella

Experimental group

Description:

Glabella Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Frontal

Experimental group

Description:

Frontal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Temporal

Experimental group

Description:

Temporal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Occipital

Experimental group

Description:

Occipital Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Paraspinal

Experimental group

Description:

Paraspinal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Trapezius

Experimental group

Description:

Trapezius Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Change in frequency of headache days

Experimental group

Description:

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.

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox subdermally at Week 30

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox intramuscularly at Week 6

Drug: Efficacy of Botox intramuscularly at Week 24,

Drug: Efficacy of Botox subdermally at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Change in hrs of HA on HA days

Experimental group

Description:

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.

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox subdermally at Week 30

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox intramuscularly at Week 6

Drug: Efficacy of Botox intramuscularly at Week 24,

Drug: Efficacy of Botox subdermally at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Adverse Reactions with Facial paresis

Experimental group

Description:

Facial paresis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Eyelid ptosis

Experimental group

Description:

Eyelid ptosis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Bronchitis

Experimental group

Description:

Bronchitis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Neck pain

Experimental group

Description:

Neck pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Muscle stiffness

Experimental group

Description:

Musculoskeletal stiffness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Muscular weakness

Experimental group

Description:

Muscular weakness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Myalgia

Experimental group

Description:

Myalgia as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Muscle pain

Experimental group

Description:

Musculoskeletal pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Muscle spasms

Experimental group

Description:

Muscle spasms as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions Injection site pain

Experimental group

Description:

Injection site pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly

Adverse Reactions with Hypertension

Experimental group

Description:

Hypertension as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30.

Treatment:

Drug: Adverse Reactions of Botox subdermally

Drug: Adverse Reactions of Botox intramuscularly