Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer.Phase 1/2ASISinCMNCT02074163
ASIS for Botox in Chronic Migraine
A Phase 1/2 study testing Gadolinium, Efficacy of Botox intramuscularly at Week 6 and Efficacy of Botox intramuscularly at Week 12 in people with Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer., run by ASIS Corporation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer.
- What is being tested?
- Gadolinium, Efficacy of Botox intramuscularly at Week 6 and Efficacy of Botox intramuscularly at Week 12
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to Jun 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Automatic Subdermal Injector System, Inc
Westminster, California, 92683
Li Nguyen, MD, 714-453-7857, dr.li.nguyen@asis-inc.com
Thanh Phung, MD, (714)-893-1915, thanhphung@idit-inc.com
About this study
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.
Read the 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.
- Being tested
- Gadolinium, 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,
- Keywords
- Subdermal bloodless space, Subdermal injection, injectable EMG needle, electrical stimulation, MRI with Gadolinium, Chronic Migraine, intramuscular injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GadoliniumDrug
Also called Gadolinium Magnevist® (gadopentetate dimeglumine)
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.
GadoliniumDrug
Also called Gadolinium Magnevist® (gadopentetate dimeglumine)
Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.
Efficacy of Botox intramuscularly at Week 6Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox intramuscularly at Week 12Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox intramuscularly at Week 18Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox intramuscularly at Week 24,Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox intramuscularly at Week 30Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox subdermally at Week 6Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox subdermally at Week 12Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox subdermally at Week 18Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox subdermally at Week 24Drug
Also called Botox (onabotulinumtoxinA)
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.
Efficacy of Botox subdermally at Week 30Drug
Also called Botox (onabotulinumtoxinA)
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 intramuscularlyDrug
Also called Botox (onabotulinumtoxinA)
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.
Adverse Reactions of Botox subdermallyDrug
Also called Botox (onabotulinumtoxinA)
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.
| Study group | Role | What they receive |
|---|---|---|
| Glabella | Experimental | Glabella
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| Frontal | Experimental | Frontal
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| Temporal | Experimental | Temporal
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| Occipital | Experimental | Occipital
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| Paraspinal | Experimental | Paraspinal
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| Trapezius | Experimental | Trapezius
Gadolinium Magnevist® (gadopentetate dimeglumine)
.1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. Receives: Drug: Gadolinium |
| 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. Receives: 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 |
| 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. Receives: 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 |
| Adverse Reactions with Facial paresis | Experimental | Facial paresis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Eyelid ptosis | Experimental | Eyelid ptosis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Bronchitis | Experimental | Bronchitis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Neck pain | Experimental | Neck pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Muscle stiffness | Experimental | Musculoskeletal stiffness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Muscular weakness | Experimental | Muscular weakness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Myalgia | Experimental | Myalgia as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Muscle pain | Experimental | Musculoskeletal pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Muscle spasms | Experimental | Muscle spasms as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions Injection site pain | Experimental | Injection site pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
| Adverse Reactions with Hypertension | Experimental | Hypertension as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. Receives: Drug: Adverse Reactions of Botox intramuscularly; Drug: Adverse Reactions of Botox subdermally |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2014 (estimated)
- Study startJan 2016
- Primary completionJun 2016 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer.Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ASIS Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Li Nguyen, MD, Principal investigator, AUTOMATIC SUBDERMAL INJECTOR SYSTEM INCThanh Phung, MD, Principal investigator, AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02074163
- Sponsor's protocol ID
- NCTNS088800
- Other IDs
- R01NS088800
- Acronym
- ASISinCM
- Status last verified
- Jun 2015
- First submitted
- 26 Feb 2014
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bartleson JD, Cutrer FM. Migraine update. Diagnosis and treatment. Minn Med. 2010 May;93(5):36-41.
PubMed 20572569Lorenc 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.
PubMed 23515199Knopp 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.
PubMed 16763467Montagna P. Migraine genetics. Expert Rev Neurother. 2008 Sep;8(9):1321-30. doi: 10.1586/14737175.8.9.1321.
PubMed 18759544Robbins 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.
PubMed 20352581Levy 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.
PubMed 19545256Cousins 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.
PubMed 21649653Olesen 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.
PubMed 19539239
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ASIS for Botox in Chronic Migraine
- ClinicalTrials.gov ID
- NCT02074163
- Acronym / sponsor ID
- ASISinCM / NCTNS088800
- Keywords
- Subdermal bloodless space, Subdermal injection, injectable EMG needle, electrical stimulation, MRI with Gadolinium, Chronic Migraine, intramuscular injection
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- ASIS CorporationIndustry (pharma, biotech, devices)
- Study start
- Jan 2016
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 28 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| Glabella | Experimental | Drug: GadoliniumGlabella Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Frontal | Experimental | Drug: GadoliniumFrontal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Temporal | Experimental | Drug: GadoliniumTemporal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Occipital | Experimental | Drug: GadoliniumOccipital Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Paraspinal | Experimental | Drug: GadoliniumParaspinal Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9ccNS intramuscularly for 30 patients, and subdermally with ASIS Device for 30 patients. |
| Trapezius | Experimental | Drug: GadoliniumTrapezius 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 | 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 30Change 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 | 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 30Change 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 | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyFacial paresis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Eyelid ptosis | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyEyelid ptosis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Bronchitis | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyBronchitis as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Neck pain | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyNeck pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Muscle stiffness | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyMusculoskeletal stiffness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Muscular weakness | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyMuscular weakness as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Myalgia | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyMyalgia as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Muscle pain | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyMusculoskeletal pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Muscle spasms | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyMuscle spasms as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions Injection site pain | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyInjection site pain as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
| Adverse Reactions with Hypertension | Experimental | Drug: Adverse Reactions of Botox intramuscularly, Drug: Adverse Reactions of Botox subdermallyHypertension as Adverse Reactions of Botox intramuscularly vs.Adverse Reactions of Botox subdermally at Week 30. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GadoliniumAlso: Gadolinium Magnevist® (gadopentetate dimeglumine)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. | Drug | Frontal, Glabella, Occipital, Paraspinal, Temporal, Trapezius |
| GadoliniumAlso: Gadolinium Magnevist® (gadopentetate dimeglumine)Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI. | Drug | Frontal, Glabella, Occipital, Paraspinal, Temporal, Trapezius |
| Efficacy of Botox intramuscularly at Week 6Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox intramuscularly at Week 12Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox intramuscularly at Week 18Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox intramuscularly at Week 24,Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox intramuscularly at Week 30Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox subdermally at Week 6Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox subdermally at Week 12Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox subdermally at Week 18Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox subdermally at Week 24Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Efficacy of Botox subdermally at Week 30Also: Botox (onabotulinumtoxinA)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. | Drug | Change in frequency of headache days, Change in hrs of HA on HA days |
| Adverse Reactions of Botox intramuscularlyAlso: Botox (onabotulinumtoxinA)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. | Drug | Adverse Reactions Injection site pain, Adverse Reactions with Bronchitis, Adverse Reactions with Eyelid ptosis, Adverse Reactions with Facial paresis, Adverse Reactions with Hypertension, Adverse Reactions with Muscle pain, Adverse Reactions with Muscle spasms, Adverse Reactions with Muscle stiffness, Adverse Reactions with Muscular weakness, Adverse Reactions with Myalgia, Adverse Reactions with Neck pain |
| Adverse Reactions of Botox subdermallyAlso: Botox (onabotulinumtoxinA)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. | Drug | Adverse Reactions Injection site pain, Adverse Reactions with Bronchitis, Adverse Reactions with Eyelid ptosis, Adverse Reactions with Facial paresis, Adverse Reactions with Hypertension, Adverse Reactions with Muscle pain, Adverse Reactions with Muscle spasms, Adverse Reactions with Muscle stiffness, Adverse Reactions with Muscular weakness, Adverse Reactions with Myalgia, Adverse Reactions with Neck pain |
Primary outcome
Relative Prolongation Ability Score for Gadolinium subdermally injected.
Time frame: 12 months
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.
1 secondary outcome
Efficacy of Botox intramuscularly vs. subdermally in Chronic Migraine.
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2015.
- Background: PubMed 20572569Bartleson JD, Cutrer FM. Migraine update. Diagnosis and treatment. Minn Med. 2010 May;93(5):36-41.
- Background: PubMed 23515199Lorenc 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.
- Background: PubMed 16763467Knopp 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.
- Background: PubMed 18759544Montagna P. Migraine genetics. Expert Rev Neurother. 2008 Sep;8(9):1321-30. doi: 10.1586/14737175.8.9.1321.
- Background: PubMed 20352581Robbins 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.
- Background: PubMed 19545256Levy 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.
- Background: PubMed 21649653Cousins 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.
- Background: PubMed 19539239Olesen 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li Nguyen, MD principal investigator
AUTOMATIC SUBDERMAL INJECTOR SYSTEM INC
Thanh Phung, MD principal investigator
AUTOMATIC SUBDERMAL INJECTOR SYSTEM, INC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gadolinium, Efficacy of Botox intramuscularly at Week 6 and Efficacy of Botox intramuscularly at Week 12 in people with Chronic Migraine More than15 Days Per Month, and Lasting 4 Hours a Day or Longer., run by ASIS Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li Nguyen, MD ((714)-453-7857, dr.li.nguyen@asis-inc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Prolongation Ability Score for Gadolinium subdermally injected. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02074163, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2015.