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

Phase 2
Completed
Conditions
Raynaud's Disease
Interventions
Drug: onabotulinum toxin type-A
Registration Number
NCT01309802
Lead Sponsor
Southern Illinois University
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
onabotulinum toxin type-Aonabotulinum toxin type-Aup 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
Primary Outcome Measures
NameTimeMethod
Percentage of Patient Reported Pain-free Daysbaseline to 28 days

Subjective pain scales \[visual analogue scale (VAS) and faces pain assessment\]. Subjects reporting total number of pain free days within the time period of 0-28 days.

Secondary Outcome Measures
NameTimeMethod
Hand Functionbaseline to 28 days

Quick-DASH (Disabilities of the Arm, Shoulder, and Hand) Outcome Measure

Patient Satisfactionbaseline to 28 days

The Optum SF-12v2® Health Survey - A Short Patient Reported Survey Measuring Health Using Excellent, Very Good, Good, Fair and Poor Indicators. On a scale from Excellent to Poor, Excellent being the maximum outcome. Good is scored as average. Patient satisfaction assessed as the percentage of participants who responded; Excellent, Very Good and Good on the health survey on average feeling between baseline and 28 days.

Tissue Perfusionbaseline to 28 days

Doppler perfusion imager and Periscan image analysis software

Pain Related Quality of Lifechange from baseline to 28 days

SF-12v2® Health Survey - Pain Enhanced

EQ-5D A Standardised Patient Reported Measure of Health Status for Clinical and Economic Appraisalbaseline to 28 days

A combined reported score measuring 5 dimensions; mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels; no problems, some problems, extreme problems

Trial Locations

Locations (1)

Southern Illinois University School of Medicine

🇺🇸

Springfield, Illinois, United States

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