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Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome

Primary Purpose

Scleroderma, Raynaud's Syndrome

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Onabotulinumtoxin A
sterile saline solution
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Scleroderma focused on measuring Scleroderma, Systemic, Raynaud Disease, Botulinum Toxins, Type A

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged 18 years and older
  • Diagnosed with scleroderma.
  • Symptoms of Raynaud's syndrome affecting both hands (not necessarily to equal extents)
  • Ability to return/be available for follow-up evaluations
  • Able and willing to give informed consent
  • Able to speak and read in the English language.

Exclusion Criteria:

  • A history of Myasthenia gravis.
  • Reported allergy or hypersensitivity to any Botulinum toxin preparation.
  • Active infection in either hand.
  • Patients who have ever received Botulinum toxin vaccine.
  • Pregnant or lactating women.
  • Females unable or unwilling to maintain abstinence or use contraception for 28 days following the injections.
  • Patients who have previously undergone any vascular surgery on the upper extremity, including surgical sympathectomies.
  • Current use of any aminoglycoside antibiotic

Sites / Locations

  • Johns Hopkins Bayview Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Onabotulinumtoxin A

Placebo

Arm Description

One hand of each patient will be randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL). Injections are performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

One hand of each patient will be randomly selected for injection of sterile saline solution (placebo). Injections are performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

Outcomes

Primary Outcome Measures

Change in Digital Blood Flow From Pre- to Post-injection.
The primary outcome measure is change in blood flow to the fingers, from a pre-injection baseline to post-injection follow-up visit as measured by non-invasive laser Doppler imaging.

Secondary Outcome Measures

Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
Raynaud's Condition Score is a patient-reported, validated outcomes scale that measures the severity of Raynaud's phenomenon on a scale of 0 ("No difficulty") to 10 ("Extreme difficulty"), where higher values represent a worse outcome. Data from each weekly report were combined using a statistical model (generalized linear population-average model) to calculate a weekly rate of change for each participant's hand, where a negative value represents a improvement over time and a positive value represents worsening over time.
Number of Ulcers as Measure of Digital Ulcer Healing
A secondary outcome of this study is the number of digital ulcers as determined by clinical examination. Mean number of ulcers was calculated as total number of ulcers / total number of hands in each group.
Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported Quick-DASH score. The Quick-DASH scores measures the degree of hand and upper extremity function on a scale of 0 (not limited) to 100 (severely limited) where a higher value represents a worse outcome.
Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
A secondary outcome of this study is the patient-reported sensitivity to coldness as measured by the McCabe Cold Sensitivity score. Patients' answers on this validated instrument are scored on a scale from 0 (no sensitivity) to 400 (extreme sensitivity), where a higher number represents a worse outcome.
Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
A secondary outcome of this study is pain as measured by the validated visual-analog scale (VAS) for pain. The VAS pain instrument measures pain on a scale from 0 cm (no pain) to 10 cm (extreme pain)

Full Information

First Posted
June 11, 2014
Last Updated
October 28, 2016
Sponsor
Johns Hopkins University
Collaborators
Allergan
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1. Study Identification

Unique Protocol Identification Number
NCT02165111
Brief Title
Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome
Official Title
A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Johns Hopkins University
Collaborators
Allergan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized, double-blinded, clinical trial assessing the therapeutic efficacy of Botulinum toxin A (Onabotulinumtoxin A) in treating scleroderma-associated Raynaud's syndrome. Each patient will undergo injection with a treatment dose of Botulinum toxin A in one randomly-selected hand, and the contralateral hand will be injected with sterile saline (placebo) to serve as a control. Study participants at the first study visit will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging to assess blood flow. After this initial assessment, the patients will undergo peri-arterial injection of Botulinum toxin A in one hand, and of sterile saline solution (placebo) in the other, in a randomized, blinded manner. Patient will report the severity of their Raynaud's symptoms weekly over the four month study period. At one month post-injection, the patient will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging. At four months post-injection, the patient will again complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging. In addition, patient will be given the option of one week post-injection visit, at which point the same assessment will be performed. At the conclusion of the study, unblinding will occur.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Scleroderma, Raynaud's Syndrome
Keywords
Scleroderma, Systemic, Raynaud Disease, Botulinum Toxins, Type A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Onabotulinumtoxin A
Arm Type
Experimental
Arm Description
One hand of each patient will be randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL). Injections are performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One hand of each patient will be randomly selected for injection of sterile saline solution (placebo). Injections are performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).
Intervention Type
Drug
Intervention Name(s)
Onabotulinumtoxin A
Other Intervention Name(s)
Botox, Botulinum toxin, Dysport
Intervention Type
Drug
Intervention Name(s)
sterile saline solution
Other Intervention Name(s)
Saline
Primary Outcome Measure Information:
Title
Change in Digital Blood Flow From Pre- to Post-injection.
Description
The primary outcome measure is change in blood flow to the fingers, from a pre-injection baseline to post-injection follow-up visit as measured by non-invasive laser Doppler imaging.
Time Frame
Measured pre-injection and at one month post-injection.
Secondary Outcome Measure Information:
Title
Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
Description
Raynaud's Condition Score is a patient-reported, validated outcomes scale that measures the severity of Raynaud's phenomenon on a scale of 0 ("No difficulty") to 10 ("Extreme difficulty"), where higher values represent a worse outcome. Data from each weekly report were combined using a statistical model (generalized linear population-average model) to calculate a weekly rate of change for each participant's hand, where a negative value represents a improvement over time and a positive value represents worsening over time.
Time Frame
Weekly rate of change over the four-month study period.
Title
Number of Ulcers as Measure of Digital Ulcer Healing
Description
A secondary outcome of this study is the number of digital ulcers as determined by clinical examination. Mean number of ulcers was calculated as total number of ulcers / total number of hands in each group.
Time Frame
Measured at one month post-injection.
Title
Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
Description
A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported Quick-DASH score. The Quick-DASH scores measures the degree of hand and upper extremity function on a scale of 0 (not limited) to 100 (severely limited) where a higher value represents a worse outcome.
Time Frame
Measured at one month post-injection.
Title
Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
Description
A secondary outcome of this study is the patient-reported sensitivity to coldness as measured by the McCabe Cold Sensitivity score. Patients' answers on this validated instrument are scored on a scale from 0 (no sensitivity) to 400 (extreme sensitivity), where a higher number represents a worse outcome.
Time Frame
Measured at one month post-injection.
Title
Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
Description
A secondary outcome of this study is pain as measured by the validated visual-analog scale (VAS) for pain. The VAS pain instrument measures pain on a scale from 0 cm (no pain) to 10 cm (extreme pain)
Time Frame
Measured at one month post-injection.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 years and older Diagnosed with scleroderma. Symptoms of Raynaud's syndrome affecting both hands (not necessarily to equal extents) Ability to return/be available for follow-up evaluations Able and willing to give informed consent Able to speak and read in the English language. Exclusion Criteria: A history of Myasthenia gravis. Reported allergy or hypersensitivity to any Botulinum toxin preparation. Active infection in either hand. Patients who have ever received Botulinum toxin vaccine. Pregnant or lactating women. Females unable or unwilling to maintain abstinence or use contraception for 28 days following the injections. Patients who have previously undergone any vascular surgery on the upper extremity, including surgical sympathectomies. Current use of any aminoglycoside antibiotic
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott D Lifchez, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21868066
Citation
Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud's phenomenon: a review. Semin Arthritis Rheum. 2012 Feb;41(4):599-603. doi: 10.1016/j.semarthrit.2011.07.006. Epub 2011 Aug 24.
Results Reference
background
PubMed Identifier
28426903
Citation
Bello RJ, Cooney CM, Melamed E, Follmar K, Yenokyan G, Leatherman G, Shah AA, Wigley FM, Hummers LK, Lifchez SD. The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Arthritis Rheumatol. 2017 Aug;69(8):1661-1669. doi: 10.1002/art.40123. Epub 2017 Jun 26.
Results Reference
derived

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Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome

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