Investigation of the Efficacy and Safety of IncobotulinumtoxinA (Xeomin) in Parkinson's Tremor: A Customized Approach

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02419313
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The scientific aim of this study is to investigate the efficacy and safety of incobotulinumtoxinA (Xeomin-Merz Pharmaceuticals) in the tremor of Parkinson"s disease. Our hypothesis is that injection of Xeomin into the muscles of arm, forearm and hand decreases the tremor amplitude and frequency leading to improvement of the patient"s function.

Condition or Disease	Intervention/Treatment	Phase
Parkinson; Tremor	Drug: incobotulinumtoxinA; Drug: Saline	Phase 2

Detailed Description

This is an investigator initiated, randomized, double blind, placebo controlled, cross over study which is supported by Merz pharmaceuticals. Patients with Parkinson"s disease (at Yale Neurology and Movement disorders clinics) will be approached by the members of the research team (PI and sub-investigators) to see if they meet inclusion and exclusion criteria and wish to participate in the study.

If eligible and consented to participate in the study, there will be a series of questionaires, examinations and treatment sessions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Investigation of the Efficacy and Safety of IncobotulinumtoxinA (Xeomin) in Parkinson's Disease Tremor: A Customized Approach
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Placebo, then Xeomin Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline.	Drug: incobotulinumtoxinA; Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.; Other Names: Xeomin ; Drug: Saline; same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.; Other Names: Placebo
Active Comparator: Xeomin, then Placebo Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment.	Drug: incobotulinumtoxinA; Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.; Other Names: Xeomin ; Drug: Saline; same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale [4 weeks]

   The primary outcome measure in this protocol is significant improvement of tremor (equal or over 2 grade improvement) of the Unified Parkinson's Disease Rating Scale 4 weeks after Xeomin injection. The score is 0 to 4 , ) being no tremor and 4 severe tremor. The higher the score, the more severe the tremor.

Secondary Outcome Measures

1. Number of Patients Whose Patient Global Impression of Change (PGIC) Improved [4 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 6 or above on the PGIC 6 weeks after treatment.

2. Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale [4 Weeks]

   This scale measures the amplitude of the tremor. For instance tremor of more than 4cm oscillation is grade 4. UPDRS tremor scale is 0-4 , 4 being severe tremor. Significant improvement for this protocol considered two grades of improvement .

Eligibility Criteria

Criteria

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

Inclusion Criteria.

1. Age more than 18 years

2. Both sexes

3. all races/ethnic groups.

4. Meeting the clinical diagnosis of Parkinson's disease with presence of moderate to severe Parkinson tremor that is refractory to standard medical treatments and which limits the patient"s functionality and/or poses significant discomfort.

5. Subjects who are able to read, speak, and understand English.

Exclusion Criteria.

1. Existing significant acute medical condition (i.e. cardiovascular, endocrine, hematologic, neoplastic, infectious, or autoimmune disorders) or significant swallowing or breathing difficulties.

2. Pregnancy or planned pregnancy (determined by urine pregnancy test).

3. Active breast feeding.

4. Enrollment in any clinical trial (currently or within the past 3 months) in which treatments are imposed by a protocol.

5. Any subject for whom botulinum toxin treatment would be contraindicated; known allergy or sensitivity to medication.

6. Subjects who are younger than 18 years of age. Neuromuscular-junction disorders.

7. Evidence of acute pathology in neuro-imaging.

8. Axis I diagnosis determined by a neurologist or psychiatrist.

9. Use of Anesthetic medications within two weeks and corticosteroid injections within 4 weeks of enrollment.

10. Those who received botulinum toxin injections in the past 4 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Neurology	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University

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: NCT02419313
• Other Study ID Numbers: 1206010370
• First Posted: Apr 17, 2015
• Last Update Posted: Mar 14, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Yale University: Tremor; Parkinson; botulinum; Xeomin
• Additional relevant MeSH terms: Parkinson Disease; Tremor; incobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	Placebo First, Then Incobotulinumtoxin A	Incobotulinumtoxin A First, Then Placebo
Arm/Group Description	Subjects will all receive injections with saline first. At 12 weeks, these subjects will then cross over and receive Xeomin in the same distribution as their second treatment.	Subjects will all receive injections with incobotulinumtoxinA injections first. At 12 weeks, these subjects will then cross over and receive placebo in the same distribution as their second treatment.
Period Title: First Intervention
STARTED	18	15
COMPLETED	16	15
NOT COMPLETED	2	0
Period Title: First Intervention
STARTED	16	15
COMPLETED	15	15
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All participants included in this crossover design.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 60%
>=65 years	12 40%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61.7
Sex: Female, Male (Count of Participants)
Female	6 20%
Male	24 80%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Unified Parkinsons Disease Rating Scale (UPDRS) Tremor Scale
Description	The primary outcome measure in this protocol is significant improvement of tremor (equal or over 2 grade improvement) of the Unified Parkinson's Disease Rating Scale 4 weeks after Xeomin injection. The score is 0 to 4 , ) being no tremor and 4 severe tremor. The higher the score, the more severe the tremor.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo, Saline	incobotulinumtoxinA, Xeomin
Arm/Group Description	Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline. Saline: same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.	Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment. incobotulinumtoxinA: Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.
Measure Participants	30	30
Number [participants]	0 0%	8 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saline, incobotulinumtoxinA, Xeomin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Number of Patients Whose Patient Global Impression of Change (PGIC) 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 6 or above on the PGIC 6 weeks after treatment.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo, Saline	incobotulinumtoxinA, Xeomin
Arm/Group Description	Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline. Saline: same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.	Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment. incobotulinumtoxinA: Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.
Measure Participants	30	30
Number [participants]	0 0%	10 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saline, incobotulinumtoxinA, Xeomin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Patients With Significant Improvement in Unified Parkinsons Disease Rating Tremor Scale
Description	This scale measures the amplitude of the tremor. For instance tremor of more than 4cm oscillation is grade 4. UPDRS tremor scale is 0-4 , 4 being severe tremor. Significant improvement for this protocol considered two grades of improvement .
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo, Saline	incobotulinumtoxinA, Xeomin
Arm/Group Description	Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline. Saline: same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.	Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment. incobotulinumtoxinA: Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.
Measure Participants	30	30
Number [participants]	0 0%	8 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saline, incobotulinumtoxinA, Xeomin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0105
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	6 months Every 4 weeks regular check up Patient to call immediately if adverse effect happened
Adverse Event Reporting Description	as above
Arm/Group Title	Placebo, Saline		incobotulinumtoxinA, Xeomin
Arm/Group Description	Subjects randomized to receive the placebo ( saline) will receive an equivalent volume as the active study drug (1cc). The injections will be into -10 hand and forearm muscles. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. The subject will then cross over to an Active Intervention arm to receive incobotulinumtoxinA which will be injected in the same pattern as the saline. Saline: same volume as injected for incobotulinum toxin A into forearm muscles under EMG guidance.		Subjects will all receive injections with incobotulinumtoxinA injections, 100unit/cc into 6-10 muscles of the forearm. A series of rating scale and an examination will take place prior to treatment and at 4 and 8 weeks post treatment. These subjects will then cross over and receive placebo ( saline) in the same distribution as their second treatment. incobotulinumtoxinA: Subjects randomized to the active drug intervention arm will receive incobotulinumtoxinA (Xeomin). A series of rating scales and examinations will take place prior to treatment and for 24 weeks after treatment. At 12 weeks the subjects will cross over to the placebo (saline) arm.
All Cause Mortality
	Placebo, Saline		incobotulinumtoxinA, Xeomin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo, Saline		incobotulinumtoxinA, Xeomin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Placebo, Saline		incobotulinumtoxinA, Xeomin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/33 (9.1%)		3/33 (9.1%)
Musculoskeletal and connective tissue disorders
muscle weakness	3/33 (9.1%)	3	3/33 (9.1%)	3

Limitations/Caveats

[Not Specified]

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.