Clinical trial NCT01309802: A Two-Part Study of BOTOX® Therapy for Ischemic Digits
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Raynaud's Disease
Keywords: 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
Lead sponsor: Southern Illinois University
Sponsor class: OTHER
First posted: 2011-03-07
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Patient Reported Pain-free Days
timeFrame: baseline to 28 days
Secondary outcomes:
measure: Pain Related Quality of Life
timeFrame: change from baseline to 28 days
measure: Hand Function
timeFrame: baseline to 28 days
measure: Patient Satisfaction
timeFrame: baseline to 28 days
measure: Tissue Perfusion
timeFrame: baseline to 28 days
measure: EQ-5D A Standardised Patient Reported Measure of Health Status for Clinical and Economic Appraisal
timeFrame: baseline to 28 days
Other outcomes:
Locations:
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
Study officials:
affiliation: Southern Illinois University School of Medicine
name: Michael W Neumeister, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neumeister MW. Botulinum toxin type A in the treatment of Raynaud's phenomenon. J Hand Surg Am. 2010 Dec;35(12):2085-92. doi: 10.1016/j.jhsa.2010.09.019.
citation: Neumeister MW, Chambers CB, Herron MS, Webb K, Wietfeldt J, Gillespie JN, Bueno RA Jr, Cooney CM. Botox therapy for ischemic digits. Plast Reconstr Surg. 2009 Jul;124(1):191-201. doi: 10.1097/PRS.0b013e3181a80576.
citation: Sycha T, Graninger M, Auff E, Schnider P. Botulinum toxin in the treatment of Raynaud's phenomenon: a pilot study. Eur J Clin Invest. 2004 Apr;34(4):312-3. doi: 10.1111/j.1365-2362.2004.01324.x. No abstract available.
citation: Van Beek AL, Lim PK, Gear AJL, Pritzker MR. Management of vasospastic disorders with botulinum toxin A. Plast Reconstr Surg. 2007 Jan;119(1):217-226. doi: 10.1097/01.prs.0000244860.00674.57.
citation: Fregene A, Ditmars D, Siddiqui A. Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud's phenomenon. J Hand Surg Am. 2009 Mar;34(3):446-52. doi: 10.1016/j.jhsa.2008.11.026.