Clinical trial NCT02165111: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Scleroderma
Raynaud's Syndrome
Keywords: Scleroderma, Systemic
Raynaud Disease
Botulinum Toxins, Type A
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2014-06-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Digital Blood Flow From Pre- to Post-injection.
timeFrame: Measured pre-injection and at one month post-injection.
Secondary outcomes:
measure: Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
timeFrame: Weekly rate of change over the four-month study period.
measure: Number of Ulcers as Measure of Digital Ulcer Healing
timeFrame: Measured at one month post-injection.
measure: Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
timeFrame: Measured at one month post-injection.
measure: Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
timeFrame: Measured at one month post-injection.
measure: Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
timeFrame: Measured at one month post-injection.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Scott D Lifchez, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.