A Two-Part Study of BOTOX® Therapy for Ischemic Digits

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Michael Neumeister, MD, Southern Illinois University
ClinicalTrials.gov Identifier:
NCT01309802
First received: March 4, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

Treating patients with Raynaud's phenomenon who have chronic pain and ulcerations is extremely challenging. Published reports and our previous work support our hypothesis that symptomatic patients experience relief of pain and healing of ulcerations with minimal adverse effects when treated with botulinum toxin type A (Btx-A) injections for Raynaud's phenomenon. The proposed study is the first clinical trial and prospective study designed to document whether or not 1) Btx-A injection relieves pain in a patient's hand affected with Raynaud's disease better than a placebo within 28 days of injection, and 2) Btx-A injection relieves pain associated with Raynaud's disease for longer than 28 days, improving patients' quality of life. Through this study we intend to further determine the effect of injected Btx-A on relieving chronic pain and ulcerations to the ischemic hand while characterizing the patients for whom this treatment is most effective.


Condition Intervention Phase
Raynaud's Disease
Drug: onabotulinum toxin type-A
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 28-Day Randomized, Double-Blind, Placebo-Controlled Clinical Trial and 5-Year Prospective Outcomes Study: A Two-Part Study of BOTOX® Therapy for Ischemic Digits

Resource links provided by NLM:


Further study details as provided by Southern Illinois University:

Primary Outcome Measures:
  • number of pain-free days [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    Subjective pain scales [visual analogue scale (VAS) and faces pain assessment]


Secondary Outcome Measures:
  • quality of life [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    SF-12v2® Health Survey - Pain Enhanced

  • hand function [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    Quick-DASH (Disabilities of the Arm, Shoulder, and Hand) Outcome Measure

  • patient satisfaction [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    SF-12v2® Health Survey - Pain Enhanced

  • tissue perfusion [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    Doppler perfusion imager and Periscan image analysis software

  • quality-adjusted life-years [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
    EuroQol (EQ-5D)


Estimated Enrollment: 40
Study Start Date: May 2011
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: placebo
no intervention
Active Comparator: onabotulinum toxin type-A
up to 4 injections per hand dosage per injection: 100 units diluted in 2.0 mL normal saline; dosing will not exceed 360 units in a 3 month interval frequency: no less than 28 days between injections duration: during Study Year 1
Drug: onabotulinum toxin type-A
up to 4 injections per hand dosage per injection: 100 units diluted in 2.0 mL normal saline; dosing will not exceed 360 units in a 3 month interval frequency: no less than 28 days between injections duration: during Study Year 1
Other Names:
  • BOTOX®
  • botulinum toxin type A

Detailed Description:

PROJECT SUMMARY OVERVIEW: Treating patients with Raynaud's phenomenon who have chronic pain and ulcerations is extremely challenging. Pharmacologic vasodilators and surgical sympathectomies offer variable benefits. Case reports, small retrospective outcomes studies, and our previous work documenting symptomatic patients treated with botulinum toxin type A (Btx-A) injections for Raynaud's phenomenon have demonstrated relief of pain and healing of ulcerations with minimal adverse effects. We propose to conduct the first clinical trial and prospective study documenting the efficacy of this novel treatment modality.

STUDY AIMS: The aims of this proposal are to 1) examine the short-term efficacy of Btx-A injection compared to placebo in treating pain associated with digit ischemia due to Raynaud's disease, and 2) describe the long-term efficacy of Btx-A injection in treating pain associated with digit ischemia due to Raynaud's disease by measuring patient satisfaction and quality of life changes over time.

APPROACH: Two groups of patients will be enrolled: Group 1 will consist of patients with primary Raynaud's disease (n=20) and Group 2 of patients with secondary Raynaud's (n=20). Comparisons between treatment (Btx) and placebo (saline) will occur during the first 28 days to determine Btx-A's short-term efficacy. Follow-up visits will occur at Days 7 and 28. Post-assessment on Day 28 marks the beginning of the longitudinal observational study of patient outcomes. Placebo will no longer be used and patients still suffering from pain will be eligible for additional Btx-A injections. Patients may receive up to 4 injections of Btx-A during the 1-year study period if pain or ulcerations recur. During the study period participants will be followed to collect data on pain-free intervals, ulcer healing, subsequent treatment choices, patient satisfaction, and changes in quality of life and hand function. Group comparisons will be made to analyze results. Further stratifications for data analysis will be made as enrollment numbers allow to control for additional demographic and disease variables. Quality-adjusted life-years will be calculated to help determine the societal and individual cost of this treatment.

HYPOTHESIS: We hypothesize that 1) Btx-A injection relieves ischemic pain associated with Raynaud's disease better than a placebo within 28 days of injection, and 2) Btx-A injection relieves ischemic pain associated with Raynaud's disease for longer than 28 days, improving patients' quality of life. Through this study we intend to further elucidate the efficacy of injected Btx-A on relieving chronic pain and ulcerations to the ischemic hand while characterizing the patients for whom this treatment is most effective. This data will help us to apply for national funding to become the coordinating center for a multi-center clinical trial. The results of this research have enormous potential to impact millions of patients who suffer with Raynaud's phenomenon.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aged 18-75 years
  • diagnosed with Raynaud's disease/phenomenon
  • ischemia not due to peripheral artery disease or other vascular disease
  • otherwise healthy individual
  • up-to-date tetanus immunization
  • ability to return/be available for follow-up evaluations
  • ability/willingness to give informed consent

Exclusion Criteria:

  • HIV/AIDS positive or otherwise immunocompromised
  • history of neuromuscular disease
  • reported allergy to BOTOX®; reported allergy to lidocaine or other local anesthetic agent
  • ever received botulinum toxin vaccine
  • ultrasound or angiogram showing digital ischemia due to blocked vessel and not Raynaud's disease
  • history or symptoms of any significant medical problem in the last year (i.e., bradycardia, impaired cardiovascular function, liver disease)
  • symptoms of infection or illness during initial enrollment
  • pregnant or lactating women
  • unable or unwilling to maintain abstinence or use contraception for 28 days following all injections
  • cognitive impairment
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309802

Locations
United States, Illinois
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
Sponsors and Collaborators
Southern Illinois University
Investigators
Principal Investigator: Michael W Neumeister, MD Southern Illinois University School of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Michael Neumeister, MD, Associate Professor, Southern Illinois University
ClinicalTrials.gov Identifier: NCT01309802     History of Changes
Other Study ID Numbers: NEU-SIUSOM-11-001
Study First Received: March 4, 2011
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southern Illinois University:
botox
raynaud's
botulinum toxin
botulinum toxin A
raynaud's disease
raynaud's syndrome
raynaud's phenomenon
ischemic digits
ischemia
botox treatment
onabotulinum
onabotulinum toxin
onabotulinum toxin type A

Additional relevant MeSH terms:
Raynaud Disease
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Botulinum Toxins, Type A
Botulinum Toxins
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014