We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02165111
First Posted: June 17, 2014
Last Update Posted: December 22, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Allergan
Information provided by (Responsible Party):
Scott D. Lifchez, Johns Hopkins University
  Purpose

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.


Condition Intervention Phase
Scleroderma Raynaud's Syndrome Drug: Onabotulinumtoxin A Drug: sterile saline solution Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome

Resource links provided by NLM:


Further study details as provided by Scott D. Lifchez, Johns Hopkins University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


  • 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.

  • 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.

  • 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.

  • 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)


Enrollment: 40
Study Start Date: January 2015
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Onabotulinumtoxin A
Other Names:
  • Botox
  • Botulinum toxin
  • Dysport
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).

Drug: sterile saline solution
Other Name: Saline

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02165111


Locations
United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Allergan
Investigators
Principal Investigator: Scott D Lifchez, MD Johns Hopkins University
  More Information

Publications:
Responsible Party: Scott D. Lifchez, Associate Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02165111     History of Changes
Other Study ID Numbers: NA_00087346
First Submitted: June 11, 2014
First Posted: June 17, 2014
Results First Submitted: September 1, 2016
Results First Posted: December 22, 2016
Last Update Posted: December 22, 2016
Last Verified: October 2016

Keywords provided by Scott D. Lifchez, Johns Hopkins University:
Scleroderma, Systemic
Raynaud Disease
Botulinum Toxins, Type A

Additional relevant MeSH terms:
Syndrome
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Raynaud Disease
Disease
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Botulinum Toxins
onabotulinumtoxinA
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents