ASIS for Botox in Cervical Dystonia (ASISinCD)

li nguyen

Status and phase: Unknown; Phase 2; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02074293

NCTNS089268

R44NS089268 (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 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 22 patient groups

Splenius

Experimental group

Description:

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

Drug: Gadolinium

Scalene

Experimental group

Description:

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

Drug: Gadolinium

Sterno-cleido-mastoid

Experimental group

Description:

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

Drug: Gadolinium

Levator Scapulae

Experimental group

Description:

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

Drug: Gadolinium

Semispinalis

Experimental group

Description:

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

Drug: Gadolinium

Trapezius

Experimental group

Description:

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

Drug: Gadolinium

Longissimus

Experimental group

Description:

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

Drug: Gadolinium

Change from Baseline in Pain Frequency

Experimental group

Description:

Change from Baseline in Pain Frequency 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 6

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 24

Drug: Efficacy of Botox intramuscularly 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 subdermally at Week 12

Change from Baseline in Pain Intensity

Experimental group

Description:

Change from Baseline in Pain Intensity 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. The severity on scales of 0(no pain) to 4(constant or extremely severe intensity).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 6

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 24

Drug: Efficacy of Botox intramuscularly 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 subdermally at Week 12

Change from Baseline in CDSS

Experimental group

Description:

Change from Baseline in CDSS 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. The CDSS or Cervical Dystonia Severity Scale quantifies the severity of abnormal head positioning and was newly devised for this study. 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).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 6

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 24

Drug: Efficacy of Botox intramuscularly 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 subdermally at Week 12

Percent of Patients with Improved PGAS

Experimental group

Description:

Percent of Patients with Improved PGAS 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. The Physician Global Assessment Scale or PGAS is a 9 category scale scoring the physician's evaluation of the patients' status compared to baseline, ranging from -4 to +4 (very marked worsening to complete improvement), with 0 indicating no change from baseline and +1 slight improvement.

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 6

Drug: Efficacy of Botox intramuscularly at Week 12

Drug: Efficacy of Botox subdermally at Week 6

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox intramuscularly at Week 24

Drug: Efficacy of Botox intramuscularly 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 subdermally at Week 12

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally

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 intramuscularly

Drug: Adverse Reactions of Botox subdermally