- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02165111
Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome
A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21224
- Johns Hopkins Bayview Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Onabotulinumtoxin A
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. |
Other Names:
|
Placebo Comparator: Placebo
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). |
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Digital Blood Flow From Pre- to Post-injection.
Time Frame: Measured pre-injection and at one month 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.
|
Measured pre-injection and at one month post-injection.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
Time Frame: Weekly rate of change over the four-month study period.
|
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. |
Weekly rate of change over the four-month study period.
|
Number of Ulcers as Measure of Digital Ulcer Healing
Time Frame: Measured at one month post-injection.
|
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.
|
Measured at one month post-injection.
|
Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
Time Frame: Measured at one month post-injection.
|
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.
|
Measured at one month post-injection.
|
Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
Time Frame: Measured at one month post-injection.
|
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.
|
Measured at one month post-injection.
|
Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
Time Frame: Measured at one month post-injection.
|
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)
|
Measured at one month post-injection.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Scott D Lifchez, MD, Johns Hopkins University
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Skin Diseases
- Disease
- Connective Tissue Diseases
- Peripheral Vascular Diseases
- Syndrome
- Scleroderma, Systemic
- Scleroderma, Diffuse
- Scleroderma, Localized
- Raynaud Disease
- 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
- Botulinum Toxins, Type A
- abobotulinumtoxinA
Other Study ID Numbers
- NA_00087346
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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