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

October 28, 2016 updated by: Scott D. Lifchez, Johns Hopkins University

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

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • Botox
  • Dysport
  • Botulinum toxin
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:
  • Saline

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

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Scott D Lifchez, MD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

June 11, 2014

First Submitted That Met QC Criteria

June 13, 2014

First Posted (Estimate)

June 17, 2014

Study Record Updates

Last Update Posted (Estimate)

December 22, 2016

Last Update Submitted That Met QC Criteria

October 28, 2016

Last Verified

October 1, 2016

More Information

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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