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

NCT02165111 | Completed Phase 3 Results DMC

• 1 other identifier: NA_00087346
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Scleroderma; Raynaud's Syndrome

Keywords

Scleroderma, Systemic; Raynaud Disease; Botulinum Toxins, Type A

Outcome Measures

Primary Outcomes (1)

• Change in Digital Blood Flow From Pre- to 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 Outcomes (5)

• Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.

  Weekly rate of change over the four-month study period.

• Number of Ulcers as Measure of Digital Ulcer Healing

  Measured at one month post-injection.

• Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.

  Measured at one month post-injection.

• Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.

  Measured at one month post-injection.

• Assessment of Raynaud's Symptom Severity Using the VAS for Pain.

  Measured at one month post-injection.

Study Arms (2)

Onabotulinumtoxin A

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Onabotulinumtoxin A DRUG

Also known as: Botox, Botulinum toxin, Dysport

Onabotulinumtoxin A

sterile saline solution DRUG

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Allergan: collaborator

Study Sites (1)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Related Publications (2)

• 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.

  PMID: 21868066 BACKGROUND

• 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.

  PMID: 28426903 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse; Raynaud Disease; Scleroderma, Systemic

Interventions

Botulinum Toxins, Type A; Botulinum Toxins; abobotulinumtoxinA; Sodium Chloride

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Multi-level data prevents conclusions from being drawn from aggregate data alone. High degree of variability of the results suggests a heterogeneous group of scleroderma patients. Screening methods and no dose escalation may explain negative findings

Results Point of Contact

• Title: Dr. Ricardo J. Bello
• Organization: Johns Hopkins University

rbello@jhmi.edu

4109557566

Study Officials

• Scott D Lifchez, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 11, 2014
• First Posted: June 17, 2014
• Study Start: January 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: December 22, 2016
• Results First Posted: December 22, 2016

Record last verified: 2016-10

Locations

US (1)