" Treating MS Patients With Lower Extremity Spasticity Using Dysport"

A Prospective, Open Label, Single Center Study of Patients With Multiple Sclerosis With Lower Extremity Spasticity Who Are Treated With Dysport

The purpose of this study is to determine whether Dysport® (abobotulinumtoxinA) injections for lower extremity spasticity showed a significant reduction of lower extremity spasticity after being injected with Dysport® (abobotulinumtoxinA) in patients with MS.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis; Spasticity, Muscle
• Intervention / Treatment: Biological: Abobotulinumtoxin A

Detailed Description

Primary Objective To evaluate the effect of Dysport® (abobotulinumtoxin A) on lower extremity spasticity (soleus, gastrocnemius, lateral gastrocnemius, medial gastrocnemius, flexor digitorum longus, flexor halluces longus, rectus femorus, vastus lateralis, lateral hamstrings, medial hamstrings, adductor magnus, adductor longus, adductor brevis, triceps surae, tibialis posterior or anterior tibialis).

Other Objectives

• To explore the effect of Dysport® on improvement in walking ability in patients with MS
• To explore the effect of Dysport® on quality of (QoL) in patients with MS. Primary Endpoint Absolute change from baseline in Modified Ashworth Scale (MAS) through 20 weeks of treatment.

Other Endpoints

• Change from baseline in MAS scores at Weeks 12, 16, and 20.
• Change from baseline on QoL based on patient reported outcome (PRO) measures on the MSWS-12, MSIS 29, pain scales (0-10 pain scale) the MSSS-88, and the Penn spasm frequency scale through 20 weeks of treatment.
• Change from baseline on the time 25 foot walk (T25FW) test with timed up and go (TUG) through 20 weeks of treatment.
• Change from baseline on expanded disability status scale (EDSS) score at Weeks 12, 16, 20.
• Change from baseline in speed, cadence, general symmetry, propulsion, stride length, T25FW, TUG using GWALK device for gait assessments through 20 weeks.
• Adverse events over 20 weeks
• Serious adverse events over 20 weeks

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sarah Cardoso; Phone Number: 101 781-551-5812; Email: sarahc@myneurodr.com

Study Locations

• United States
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Recruiting
      • Neurology Center of New England P.C.
      • Principal Investigator: Salvatore Napoli, MD
      • Contact: Sarah Cardoso; Phone Number: 101 781-551-5812; Email: sarahc@myneurodr.com
      • Sub-Investigator: Sarah Cardoso

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Subjects who meet all of the following inclusion criteria will be eligible:

1. Male or female with confirmed diagnosis of MS1 over 18 years of age.
2. Patients with a clinically definite diagnosis of MS including patients with relapsing-remitting MS, primary progressive MS, progressive relapsing MS, and secondary progressive MS based on clinical history, physical exam, current or previous brain or spine MRI, CSF analysis will be used to specify the class of MS of the patient.
3. Patients with no prior exposure to any commercial Botulinum toxin or patients that have had previous exposure to commercial Botulimun toxin no less than four months after last injection.
4. Naïve patients having a MAS score ≥1 at baseline in any of the following muscles soleus, gastrocnemius, lateral gastrocnemius, medial gastrocnemius, flexor digitorum longus, flexor halluces longus, rectus femorus, vastus lateralis, lateral hamstrings, medial hamstrings, adductor magnus, adductor longus, adductor brevis.
5. Patients with prior exposure to commercial Botulinum having a MAS ≥1 at baseline in any of the following US Dysport label muscles such as the soleus, gastrocnemius, lateral gastrocnemius, medial gastrocnemius, flexor digitorum longus, flexor halluces longus, or muscles beyond the label such as the rectus femorus, vastus lateralis, lateral hamstrings, medial hamstrings, adductor magnus, adductor longus, adductor brevis, tibialis posterior EDSS score less than 7.0.
6. Penn spasm frequency scale at baseline greater than 2.
7. Functional outcomes such as walking speed T25FW baseline walking speed greater than 0.8.

8. Subjects that have agreed to participate and have signed an informed consent form.

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Exclusion Criteria:

• Subjects who meet any of the following exclusion criteria will not be eligible:

  1. Subjects having experienced a relapse within the previous 30 days.
  2. Recently initiated treatment on antispasmodic therapy or Ampyra within 30 days of screening.
  3. Subjects that have not maintained a steady dose of baclofen or other antispasmodics in the previous 30 days will be excluded.
  4. Pregnant or women who intend to become pregnant or breastfeeding women. Women of child bearing potential are required to use oral contraceptives, condoms, intrauterine device (IUD) diaphragm, spermicide, sexual abstinence or vasectomized partner. Female patients using contraception should continue to use contraception 3- 4 months post injection. Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Using Dysport to treat lower extremity spasticty in patients diagnosed with Multiple Sclerosis. Improved walking ability and quality of life in 28 patients based on quality of life assessments and patient reported outcomes.	Using Dysport® (abobotulinumtoxin A) to treat patients diagnosed with Multiple Sclerosis with lower extremity spasticity .	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in Modified Ashworth Scale (MAS)	Mean change from baseline in Modified Ashworth Scale (MAS).. The Modified Ashworth Scale issued to grade spasticity. This scale measures the presence of velocity-dependent resistance on a 0 to 4 scale, with zero representing normal muscle tone, and four representing a limb that is fixed in flexion or extension	Baseline week 12, week 16, and week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
12 item Multiple Sclerosis Walking scale (MSWS-12) Improvement	Mean change from baseline in the 12 Item Multiple Sclerosis Walking Scale. The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS during the past 2 weeks. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores	Baseline weeks 12, 16, and 20
Improvement of (MSIS-29) Multiple Sclerosis Impact Scale	Mean change from baseline in the (MISIS-29) Multiple Sclerosis Impact Scale.The MSIS-29 is a 29 item measurement, which assesses the physical and psychological impact of MS on affected individuals; it is a self report questionnaire consisting of 20 and 9 items, respectively. Scores on the individual items are added and then transformed to a 0-100 scale, thereby generating two summary scores (for physical and psychological impact). Higher scores indicate worse health.	Baseline weeks 12,16 and 20
Improvement of Pain Scale	Mean change from baseline in the 0-10 Pain Scale. involves asking the patient to rate his or her pain from 0 to 10 (11 point scale) with the understanding that 0 is equal to no pain and 10 is equal to worst possible pain. 0 Pain free; Very minor annoyance-occasional minor twinges; Minor annoyance-occasional; Annoying enough to be distracting; Can be ignored if you are really involved in your work, but still distracting,; Can't be ignored for more than 30 minutes.; Can't be ignored for any length of time, but you can still go to work and participate in social activities.; Make it difficult to concentrate, interferes with sleep, you can still function with effort; Physical activity severely limited. You can read and converse with effort. Nausea and dizziness may occur.; Unable to speak, crying out or moaning uncontrollable- pain makes you pass out; Unconscious. Pain makes you pass out.	Baseline weeks 12,16 and 20
Improvement of (MSSS-88) Multiple Sclerosis Spasticity Scale	Mean Change from baseline in the (MSSS-88) Multiple sclerosis Spasticity scale measures patient experience and perception of the impact of spasticity in MS with day-to-day symptoms andduring functional activities over the previous two weeks. It has 88 questions to quantify spasticity for a total score and in eight clinically relevant and stand-alone subscales: muscle stiffness, pain and discomfort,muscle spasms, activities of daily living,walking, body movements, emotional health, and social functioning.This scale has 88 items that are rated on a 4-point scale of 1 (Not at all bothered) through 4 (Extremely bothered).	Baseline weeks 12,16 and 20
Improvement of the Penn Spasm frequency scale	Mean change from baseline in the Penn Spasm frequency scale. The patient evaluates his/her "spasms", quantifying them according to 5 classifications (from 0 to 4).For ratings of 1 or greater, the severity of the spasms is also be evaluated, using a 3 level scale (mild, moderate or severe)	Baseline weeks 12,16 and 20
Improvement from baseline on the Timed 25 foot walk (T25FW)	Mean change from baseline on the Timed 25 foot walk (T25FW) The Timed 25-Foot Walk test is a mobility and function test based on a timed 25-foot walk. An individual will be asked to walk 25 feet on a clearly marked course as quickly and safely as they can. The time is calculated with a stopwatch, recorded, and the individual is asked to repeat the task immediately, walking back the same distance to the their initial starting point.	Baseline weeks 12,16 and 20
Improvement of Timed up and Go	Mean change from baseline on the Timed up and go. The purpose of the Timed Up and Go test is to identify individuals who are at risk of falling. It can screen for balance and gait problems. A person is observed as they stand from a sitting position without using their arms for support, then walk 10 feet, turn and return to a chair. Finally, they sit back in the chair without using their arms for support.	Baseline weeks 12,16 and 20
Improvement on the (EDSS) score	Mean change from baseline on the Expanded Disability Status Scale (EDSS) score. is a 20 point ordinal scale ranging from 0 (normal neurological exam) to 10 (dead from MS). From 0-4.0, EDSS is determined by the combination of scores on 7 functional systems. From 4.0-6.0 EDSS is determined by the ability to walk a distance. EDSS 6.0 is the need for unilateral walking assistance. EDSS 6.5 is the need for bilateral walking assistance. Nonambulatory patients are scored EDSS ≥7.0, with higher number reflecting increasing difficulty with mobility and ability to perform self-care.	Baseline weeks 12,16 and 20
Walking improvement	Change from baseline in speed, cadence, general symmetry, propulsion, stride length using the G-Walk device is a wireless system of inertial sensors composed of a triaxial accelerometer, a magnetic sensor, and a triaxial gyroscope that, when positioned on L5 vertebrae of the spine, it allows for a functional objective gait analysis to be performed. The system extrapolates the data and calculates all the spatial-temporal gait parameters required to perform an assessment or to define a training strategy	Baseline weeks 12,16 and week 20

Collaborators and Investigators

• Sponsor: Neurology Center of New England P.C.
• Collaborators: Ipsen
• Investigators: Principal Investigator: Salvatore Q Napoli, MD, Neurology Center of New England P.C.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: March 16, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Multiple Sclerosis; Sclerosis; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: SAIRB-17-0093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Poster and Paper with at AAN and ECTRIMS intention for full manuscript

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes