ASIS for Botox in Upper Limb Spasticity (ASISinULS)

li nguyen

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Increased Muscle Tone in Elbow, Wrist, Finger, and Thumb Flexors.; Upper Limb Spasticity Unilaterally in Adults With History of Stroke

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02074150

NCTHD081800

R44HD081800 (Other Grant/Funding Number)

Details and patient eligibility

About

Botox act 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 Upper limb Spasticity. Gadolinium will be injected with ASIS subdermally (30) or conventional intramuscularly (30) for these 7 muscle groups: Biceps Brachii, Flexor Carpi Radialis, Flexor Carpi Ulnaris, Flexor Digitorum Profundus, Flexor Digitorum Sublimis, Adductor Pollicis, and Flexor Pollicis Longus. 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 Upper limb Spasticity, and these particular 7 muscle groups. Case in point, patients with Upper limb Spasticity presumably have hyperactivity in these 7 muscle groups, so expectantly will have shortened Gadolinium intramuscularly Persistent %, and somewhat reduced Gadolinium subdermally Persistent % as well due to agitation, thus these Persistent % values in Upper limb Spasticity 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 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 same 60 adult subjects with Upper limb Spasticity, on these particular 7 muscle groups: Biceps Brachii, Flexor Carpi Radialis, Flexor Carpi Ulnaris, Flexor Digitorum Profundus, Flexor Digitorum Sublimis, Adductor Pollicis, and Flexor Pollicis Longus. Hypothetically speaking, if that subdermal bloodless space in patients with e.g., Upper limb Spasticity 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 and Ashworth score (force required to move an extremity around a joint), at 6,12,18,24, and 30 weeks, and reduction in adverse reactions.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults with history of stroke that resulted in a unilateral, upper-limb focal spasticity
• Wrist flexor tone of more than 2 and finger flexor tone of more than 2 as measured by the Ashworth Scale
• Ability to understand and follow verbal directions
• At least 1 functional disability item (hygiene, dressing, pain, or limb posture) with a rating of more than 2 on the Disability Assessment Scale (DAS)
• At least 1 functional task score at Day 0 that met the following criteria: nail filing less than 6, hand cleaning less than 6, holding a water bottle less than 4, brushing teeth less than 4, holding fruit (small, medium, or large equals no.

Exclusion criteria

• Stroke within 6 months of the study enrollment visit
• Females who are pregnant, nursing, or planning a pregnancy during the study period or who are not using a reliable means of contraception
• Previous or current Botox therapy of any type in the study limb
• Any medical condition that may put the patient at increased risk with Botox exposure or any other disorder that might have interfered with neuromuscular function
• Presence of fixed contracture of the study limb
• Limited use of the wrist and fingers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 23 patient groups

Biceps Brachii

Experimental group

Description:

Biceps Brachii (elbow flexors) 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

Flexor Carpi Radialis

Experimental group

Description:

Flexor Carpi Radialis (wrist flexors) 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

Flexor carpi ulnaris

Experimental group

Description:

Flexor carpi ulnaris (wrist flexors) 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

Flexor digitorum profundus

Experimental group

Description:

Flexor digitorum profundus (finger flexors) 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

Flexor digitorum sublimis

Experimental group

Description:

Flexor digitorum sublimis (finger flexors) 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

Adductor pollicis

Experimental group

Description:

Adductor pollicis (thumb flexors) 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

Flexor pollicis longus

Experimental group

Description:

Flexor pollicis longus (thumb flexors) 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 Elbow Ashworth

Experimental group

Description:

Change from Baseline in Elbow Ashworth Scale 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. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none) 1. = Slight increase 2. = Moderate increase 3. = Considerable increase 4. = Limb rigid (very severe).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox subdermally at Week 12

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 intramuscularly at Week 24

Drug: Efficacy of Botox subdermally at Week 30

Change from Baseline in Wrist Ashworth

Experimental group

Description:

Change from Baseline in Wrist Ashworth Scale 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.Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none) 1. = Slight increase 2. = Moderate increase 3. = Considerable increase 4. = Limb rigid (very severe).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox subdermally at Week 12

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 intramuscularly at Week 24

Drug: Efficacy of Botox subdermally at Week 30

Change from Baseline in Finger Ashworth

Experimental group

Description:

Change from Baseline in Finger Ashworth Scale 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. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none) 1. = Slight increase 2. = Moderate increase 3. = Considerable increase 4. = Limb rigid (very severe).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox subdermally at Week 12

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 intramuscularly at Week 24

Drug: Efficacy of Botox subdermally at Week 30

Change from Baseline in Thumb Ashworth

Experimental group

Description:

Change from Baseline in Thumb Ashworth Scale 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. Ashworth score (the force required to move an extremity around a joint): 0 = No increase in muscle tone (none) 1. = Slight increase 2. = Moderate increase 3. = Considerable increase 4. = Limb rigid (very severe).

Treatment:

Drug: Efficacy of Botox intramuscularly at Week 30

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox subdermally at Week 12

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 intramuscularly at Week 24

Drug: Efficacy of Botox subdermally at Week 30

Change from Baseline in PGAS

Experimental group

Description:

Change from Baseline in 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 30

Drug: Efficacy of Botox intramuscularly at Week 18

Drug: Efficacy of Botox subdermally at Week 18

Drug: Efficacy of Botox subdermally at Week 24

Drug: Efficacy of Botox subdermally at Week 12

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 intramuscularly at Week 24

Drug: Efficacy of Botox subdermally at Week 30

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