ASIS for Botox in Cervical Dystonia

Abnormal Head Position and Neck Pain for These 7 Muscle Groups: Splenius,Scalene,Sterno-cleido-mastoid,Levator Scapulae,Semispinalis,Trapezius,and Longissimus. Clinical Trial

— ASISinCD  

Official title:

ASIS for Botox in Cervical Dystonia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02074293
• Other study ID #: NCTNS089268
• Secondary ID: R44NS089268
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: February 26, 2014
• Last updated: June 22, 2015
• Start date: January 2016
• Est. completion date: June 2017

Study information

• Verified date: June 2015
• Source: ASIS Corporation
• Contact: Li Nguyen, MD
• Phone: (714)-453-7857
• Email: dr.li.nguyen[@]asis-inc.com
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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. 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.

Description:

Aim 1 over 6 months will demonstrate ASIS device's consistent performance on 60 adult subjects with Cervical Dystonia. Gadolinium will be injected with ASIS subdermally (30) or conventional intramuscularly (30) for these 7 muscle groups: Splenius, Scalene, Sterno-cleido-mastoid, Levator scapulae, Semispinalis, Trapezius, and Longissimus. 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 Cervical Dystonia, and these particular 7 muscle groups. Case in point, patients with Cervical Dystonia presumably have hyperactive Splenius, Scalene, Sterno-cleido-mastoid, Levator scapulae, Semispinalis, Trapezius, and Longissimus muscles, so expectantly will have shortened Gadolinium intramuscularly Persistent %, and somewhat reduced Gadolinium subdermally Persistent % as well due to agitation, thus these Persistent % values in Cervical Dystonia patients will not be like those of normal patients, or even the same between these 7 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 Botox dosage and duration to inject into "unknown" subdermal bloodless space for Aim 2.

Aim 2 over 12 months, using Botox, instead of Gadolinium, will demonstrate the advantages of ASIS device subdermally over intramuscularly, for the same 60 adult subjects with Cervical Dystonia, on these particular 7 muscle groups: Splenius, Scalene, Sterno-cleido-mastoid, Levator scapulae, Semispinalis, Trapezius, and Longissimus. Hypothetically speaking, if that subdermal bloodless space in patients with e.g., Cervical Dystonia 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 improvement on the Physician Global Assessment Scale at 6, 12, 18, 24, and 30 weeks, and reduction in Cervical Dystonia Severity Scale (CDSS) as well as adverse reactions.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

•Adults with cervical dystonia, or abnormal head position and neck pain for these 7 muscle groups: Splenius, Scalene, Sterno-cleido-mastoid, Levator scapulae, Semispinalis, Trapezius, and Longissimus.

Exclusion Criteria:

• Known Hypersensitivity to Botulinum Toxin or to any of the components in the formulation.

• Infection at the Injection Site(s).

• 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.

• Had previously received surgical or other denervation treatment for their symptoms or had a known history of neuromuscular disorder.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Head Position and Neck Pain for These 7 Muscle Groups: Splenius,Scalene,Sterno-cleido-mastoid,Levator Scapulae,Semispinalis,Trapezius,and Longissimus.
• Cervical Dystonia Adults ,
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Drug:
• Gadolinium
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.
• Gadolinium
Gadolinium .1cc/ diluted with .9ccNS subdermally with ASIS Device for 30 patients. Total cumulative Persistent % of Gadolinium subdermally on MRI at 6 hrs, 12 hrs, and 24 hrs.
• Gadolinium
Relative Prolongation Ability Score or total Persistent % of Gadolinium subdermally over total Persistent % of Gadolinium intramuscularly on MRI.
• Efficacy of Botox intramuscularly at Week 6
Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 6, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox intramuscularly at Week 12
Efficacy of Botox intramuscularly at Week 12, in terms of Percent of Patients with Improved PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, Change from Baseline in Pain Intensity, Change from Baseline in CDSS (Cervical Dystonia Severity Scale).
• Efficacy of Botox intramuscularly at Week 18
Efficacy of Botox intramuscularly at Week 18, in terms of Percent of Patients with Improved PGAS, or improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, Change from Baseline in Pain Intensity, Change from Baseline in CDSS (Cervical Dystonia Severity Scale).
• Efficacy of Botox intramuscularly at Week 24
Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 24, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox intramuscularly at Week 30
Efficacy of Botox (onabotulinumtoxinA) intramuscularly at Week 30, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox subdermally at Week 6
Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 6, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox subdermally at Week 12
Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 12, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox subdermally at Week 18
Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 18, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox subdermally at Week 24
Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 24, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Efficacy of Botox subdermally at Week 30
Efficacy of Botox (onabotulinumtoxinA) subdermally at Week 30, in terms of improvement on the Physician Global Assessment Scale, and Change from Baseline in Pain Frequency, and Pain Intensity, as well as Cervical Dystonia Severity Scale (CDSS).
• Adverse Reactions of Botox intramuscularly
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 subdermally
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.

Locations

Country	Name	City	State
United States	Automatic Subdermal Injector System, Inc	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
li nguyen

Country where clinical trial is conducted

United States, 

References & Publications (9)

Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Dystonia rating scales: critique and recommendations. Mov Disord. 2013 Jun 15;28(7):874-83. doi: 10.1002/mds.25579. Review. — View Citation

Claypool DW, Duane DD, Ilstrup DM, Melton LJ 3rd. Epidemiology and outcome of cervical dystonia (spasmodic torticollis) in Rochester, Minnesota. Mov Disord. 1995 Sep;10(5):608-14. — View Citation

Evidente VG, Fernandez HH, LeDoux MS, Brashear A, Grafe S, Hanschmann A, Comella CL. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. J Neural Transm (Vienna). 2013 Dec;120(12):1699-707. doi: 10.1007/s00702-013-1048-3. Epub 2013 Jun 19. — View Citation

Knopp MV, Balzer T, Esser M, Kashanian FK, Paul P, Niendorf HP. Assessment of utilization and pharmacovigilance based on spontaneous adverse event reporting of gadopentetate dimeglumine as a magnetic resonance contrast agent after 45 million administrations and 15 years of clinical use. Invest Radiol. 2006 Jun;41(6):491-9. Erratum in: Invest Radiol. 2006 Sep;41(9):667. — View Citation

Leplow B, Böttcher M, Schönfeld R. [Botulinum toxin therapy for spasmodic torticollis: medical and non-medical adjunct treatment]. Nervenarzt. 2013 Apr;84(4):493-7. doi: 10.1007/s00115-012-3708-1. German. — View Citation

Lorenc ZP, Kenkel JM, Fagien S, Hirmand H, Nestor MS, Sclafani AP, Sykes JM, Waldorf HA. A review of onabotulinumtoxinA (Botox). Aesthet Surg J. 2013 Mar;33(1 Suppl):9S-12S. doi: 10.1177/1090820X12474629. Review. — View Citation

Tiderington E, Goodman EM, Rosen AR, Hapner ER, Johns MM 3rd, Evatt ML, Freeman A, Factor S, Jinnah HA. How long does it take to diagnose cervical dystonia? J Neurol Sci. 2013 Dec 15;335(1-2):72-4. doi: 10.1016/j.jns.2013.08.028. Epub 2013 Aug 30. — View Citation

Velickovic M, Benabou R, Brin MF. Cervical dystonia pathophysiology and treatment options. Drugs. 2001;61(13):1921-43. Review. — View Citation

Vivancos-Matellano F, Ybot-Gorrin I, Diez-Tejedor E. A 17-year experience of abobotulinumtoxina in cervical dystonia. Int J Neurosci. 2012 Jul;122(7):354-7. doi: 10.3109/00207454.2012.665971. Epub 2012 Mar 20. Erratum in: Int J Neurosci. 2012 Dec;122(12):767. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Reactions of Botox intramuscularly vs. subdermally in Cervical Dystonia.	Adverse Reactions of Botox intramuscularly vs. subdermally: Headache Migraine, Facial paresis, Eyelid ptosis, Bronchitis, Neck pain Musculoskeletal stiffness, Muscular weakness Myalgia, Musculoskeletal pain, Muscle spasms, Injection site pain, and Hypertension.	12 months	Yes
Primary	Relative Prolongation Ability Score for Gadolinium subdermally injected.	Gadolinium will be injected with ASIS subdermally (30) or conventional intramuscularly (30) in Cervical Dystonia adult patients for these 7 muscle groups: Splenius, Scalene, Sterno-cleido-mastoid, Levator scapulae, Semispinalis, Trapezius, and Longissimus. 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 Cervical Dystonia, and these particular 7 muscle groups. The Relative Prolongation Ability Score or total Persistent % subdermally over total Persistent % intramuscularly, in Cervical Dystonia patients will not be like those of normal patients, or even the same between these 7 different muscle groups, but valuable indicators to help us modify Botox dosage and duration to inject into "unknown" subdermal bloodless space for Aim 2.	6 months	No
Secondary	Efficacy of Botox intramuscularly vs. subdermally in Cervical Dystonia.	Efficacy of Botox intramuscularly vs. subdermally with ASIS Device at Week 6,12,18, 24, and 30; in terms of improvement on the Physician Global Assessment Scale (-4=very marked worsening to +4=very marked improvement). Also in terms of improvement, or Median Change from Baseline in Pain Frequency, Pain Intensity (0(no pain) to 4(constant or extremely severe intensity)), and Cervical Dystonia Severity Scale (CDSS). CDSS allots 1 point for each 5 degrees (or part thereof) of head deviation in each of the three planes of head movement (range of scores up to theoretical maximum of 54).	12 months	Yes

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