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

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01931878
• Collaborator: Merz North America, Inc. (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Restless Leg Syndrome	Drug: incobotulinumtoxinA; Drug: Placebo	Phase 2

Detailed Description

Please contact the PI for details about the clinical study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Investigation of Efficacy of incobotulinumtoxinA (Xeomin) in Relieving Symptoms of Restless Leg Syndrome.
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Total Restless Leg Syndrome Rating Scale Score [6 weeks]

   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)

Secondary Outcome Measures

1. Number of Patients Whose Patient Global Impression of Change (PGIC) Moderately or Much Improved [6 weeks]

   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.

Other Outcome Measures

1. Patients With Pain on Visual Analog Scale <4 [6 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Physcian Building	New Haven	Connecticut	United States	06510

Sponsors and Collaborators

• Yale University
• Merz North America, Inc.

Investigators

• Principal Investigator: Bahman Jabbari, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01931878
• Other Study ID Numbers: 1206010332
• First Posted: Aug 29, 2013
• Last Update Posted: Mar 21, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Yale University: Restless Legs Syndrome; Leg pain; Sleep; Dysesthesias; incobotulinumtoxin
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome; incobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Placebo First, Then Incobotulinumtoxin A	IncobotulinumtoxinA First, Then Placebo
Arm/Group Description	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.	The subjects will be randomized to received injections of active study drug, incobotulinumtoxinA (Xeomin) 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.
Period Title: First Intervention
STARTED	10	14
COMPLETED	9	14
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	9	14
COMPLETED	9	12
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	The subject may be randomly assigned to receive Placebo, saline 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.
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 66.7%
>=65 years	7 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.71 (12.36)
Sex: Female, Male (Count of Participants)
Female	11 52.4%
Male	10 47.6%
Region of Enrollment (participants) [Number]
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	Mean Total Restless Leg Syndrome Rating Scale Score
Description	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)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Total RLS scale score was compared between incoA injections and and saline group injections.

Arm/Group Title	Placebo	Xeomin
Arm/Group Description	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.	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.
Measure Participants	21	21
Mean (Standard Deviation) [units on a scale]	25.19 (7.82)	19.46 (9.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Xeomin
	Comments	comparison of mean RLS Scale scores between 21 incoA and 21 saline injections
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	t-test, 2 sided
	Comments

2. Other Pre-specified Outcome

Title	Patients With Pain on Visual Analog Scale <4
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Xeomin
Arm/Group Description	The subject may be randomly assigned to receive Placebo, saline 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.	The subjects will be randomized to received injections of active study drug, incobotulinumtoxinA (Xeomin) 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.
Measure Participants	21	21
Number [participants]	3 14.3%	12 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Xeomin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0088
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Patients Whose Patient Global Impression of Change (PGIC) Moderately or Much Improved
Description	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.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo , Saline	IncobotulinumtoxinA Treatment
Arm/Group Description	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.	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.
Measure Participants	21	21
Number [participants]	3 14.3%	9 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Xeomin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0855
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	Placebo , Saline		IncobotulinumtoxinA Treatment
Arm/Group Description	The subject may be randomly assigned to receive Placebo, saline 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.		The subjects will be randomized to received injections of active study drug, incobotulinumtoxinA (Xeomin) 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.
All Cause Mortality
	Placebo , Saline		IncobotulinumtoxinA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo , Saline		IncobotulinumtoxinA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Placebo , Saline		IncobotulinumtoxinA Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)

Limitations/Caveats

Relatively small number of participants. crossover not parallel design

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.