Investigation of Efficacy of incobotulinumtoxinA (Xeomin) in Relieving Symptoms of Restless Leg Syndrome.

The purpose of this research study is to compare the safety and effectiveness of local injections of botulinum toxin A (Xeomin®) to an inactive test substance (placebo) in a medical condition called Restless Leg Syndrome. This study has a double blind cross over design. Cross over means that you will have two sets of injections. The first set of injections can be either Xeomin or placebo. The order of injection will be reversed at the three month point following the first injection. Double blind means neither the investigators nor you know which one of the two (Xeomin or placebo) you received.

Study Overview

• Status: Completed
• Conditions: Restless Leg Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: incobotulinumtoxinA

Detailed Description

Please contact the PI for details about the clinical study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Physcian Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects 18- 80 years of age, both sexes, all races and ethnic groups.
• Diagnosis of restless legs syndrome
• Disease duration longer than 3 months
• Restless Leg Syndrom Rating Scale score of 11 or above (moderate and above)
• Subjects who are eligible to be treated with a botulinum toxin for a therapeutic reason based upon the physicians' clinical experience.
• Subjects who are able to read, speak, and understand English.

Exclusion Criteria:

• Existing significant acute medical condition (i.e. cardiovascular, endocrine, hematologic, neoplastic, infectious, or autoimmune disorders).
• Pregnancy or planned pregnancy (determined by urine pregnancy test). Women of childbearing age should use a reliable mode of contraception during the study period (abstinence, etc).
• Active breast feeding.
• Enrollment in any clinical trial (currently or within the past 3 months) in which treatments are imposed by a protocol.
• Any subject for whom botulinum toxin treatment would be contraindicated; known allergy or sensitivity to medication.
• Subjects who are younger than 18 years of age.
• Neuromuscular-junction disorders.
• Evidence of acute pathology by neuro-imaging.
• Axis I diagnosis determined by a neurologist or psychiatrist.
• Anesthetic medications within two weeks and corticosteroid injections within 4 weeks of enrollment.
• Subject has received botulinum toxin injections in the past 4 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo , saline; The subject may be randomly assigned to receive Placebo, saline	Drug: Placebo; The subject may be randomly assigned to receive Placebo which is an inactive test substance which has no active ingredient. In this protocol we use sterile salt water as placebo.This study has a double blind cross over design. Cross over means that you will have two sets of injections. If the first set of injections is placebo, the second injections after a three month interval will be active study drug. Double blind means neither the investigators nor the subject knows which one of the two (Xeomin or placebo) is received with the first or second injections.; Other Names: Sterile saline water
ACTIVE_COMPARATOR: IncobotulinumtoxinA Treatment; The subjects will be randomized to received injections of active study drug, incobotulinumtoxinA (Xeomin)	Drug: incobotulinumtoxinA; The subject may be randomly assigned to receive incobotulinum toxinA (Xeomin) , a neurotoxin Which is approved for use by the FDA for certain conditions. This study has a double blind cross over design. Cross over means that you will have two sets of injections. If the first set of injections is Xeomin, the second injections after a three month interval will be the inactive placebo. Double blind means neither the investigators nor the subject knows which one of the two (Xeomin or placebo) is received with the first or second injections.; Other Names: Xeomin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Restless Leg Syndrome Rating Scale Score	The Restless Legs Syndrome Rating Scale uses 10 questions, each scored 0-4, with higher scores representing more severe symptoms. Score ranges from 1-40. Scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40)	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Whose Patient Global Impression of Change (PGIC) Moderately or Much Improved	The PGIC is a 7 point scale that requires the clinician to assess how much the patient's pain has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: No change (or condition has gotten worse) (1) Almost the same, hardly any change at all (2) A little better, but no noticeable change (3) Somewhat better, but the change has not made any real difference (4) Moderately better, and a slight but noticeable change (5) Better and a definite improvement that has made a real and worthwhile difference (6) A great deal better and a considerable improvement that has made all the difference (7)improved This outcome is number of patients who chose a 5 or above on the PGIC 6 weeks after treatment.	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients With Pain on Visual Analog Scale <4	The Visual Analog Scale (VAS) consists of a line which represents the level of pain in 10 cms. The subject is required to make this line to show where your pain level is on this line (for example, at the 7cm mark). A higher score is associated with a higher level of pain. Number of patients showing a pain score of <4.	6 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Merz North America, Inc.

Publications and helpful links

General Publications

• Mittal SO, Machado D, Richardson D, Dubey D, Jabbari B. Botulinum Toxin in Restless Legs Syndrome-A Randomized Double-Blind Placebo-Controlled Crossover Study. Toxins (Basel). 2018 Sep 29;10(10):401. doi: 10.3390/toxins10100401.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: August 26, 2013
• First Submitted That Met QC Criteria: August 26, 2013
• First Posted (ESTIMATE): August 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): March 21, 2016
• Last Update Submitted That Met QC Criteria: February 23, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Sleep; Restless Legs Syndrome; Leg pain; Dysesthesias; incobotulinumtoxin
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; 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; incobotulinumtoxinA
• Other Study ID Numbers: 1206010332