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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome

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.


Detailed Summary:
Sponsor: Johns Hopkins University

Current Primary Outcome: 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.


Original Primary Outcome: Change in Digital Blood Flow From Pre- to Post-injection. [ Time Frame: Measured pre-injection and at one month, four months, and (in some patients) one week post-injection. ]

The primary outcome measure is blood flow to the fingers, as measured by non-invasive laser Doppler imaging.


Current Secondary Outcome:

  • 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)


Original Secondary Outcome:

  • Assessment of Raynaud's symptoms severity using the Raynaud's Condition Score. [ Time Frame: Measured periodically over the four month study period. ]
    A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported Raynaud's Condition Score.
  • Digital ulcer healing measured by size of ulceration and time lapsed to full healing. [ Time Frame: Measured at one month, four months, and (in some patients) one week post-injection. ]
    A secondary outcome of this study is healing of existing digital ulcerations and/or prevention of new areas of digital ulceration.
  • Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score. [ Time Frame: Measured periodically over the four month study period. ]
    A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported Quick-DASH score.
  • Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score. [ Time Frame: Measured periodically over the four month study period. ]
    A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported McCabe Cold Sensitivity score.
  • Assessment of Raynaud's Symptom Severity Using the VAS for Pain. [ Time Frame: Measured periodically over the four month study period. ]
    A secondary outcome of this study is severity of Raynaud's symptoms as measured by the visual-analog scale (VAS) for pain.


Information By: Johns Hopkins University

Dates:
Date Received: June 11, 2014
Date Started: January 2015
Date Completion:
Last Updated: October 28, 2016
Last Verified: October 2016