Raynaud's DiseasePhase 2NCT01309802
A Two-Part Study of BOTOX® Therapy for Ischemic Digits
A Phase 2 study testing onabotulinum toxin type-A in people with Raynaud's Disease, run by Southern Illinois University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Raynaud's Disease
- What is being tested?
- onabotulinum toxin type-A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to 13 Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
About this study
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
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.
Read the 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.
- Conditions
- Raynaud's Disease
- Being tested
- onabotulinum toxin type-A
- 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
- Medical subject headings
- Raynaud Disease, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
onabotulinum toxin type-ADrug
Also called BOTOX®, botulinum 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
| Study group | Role | What they receive |
|---|---|---|
| placebo | No intervention | no intervention |
| onabotulinum toxin type-A | Active comparator | 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 Receives: Drug: onabotulinum toxin type-A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patient Reported Pain-free 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.
Measured: baseline to 28 days
Secondary outcomes (5)
Pain Related Quality of Life
SF-12v2® Health Survey - Pain Enhanced
Measured: change from baseline to 28 days
Hand Function
Quick-DASH (Disabilities of the Arm, Shoulder, and Hand) Outcome Measure
Measured: baseline to 28 days
Patient Satisfaction
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.
Measured: baseline to 28 days
Tissue Perfusion
Doppler perfusion imager and Periscan image analysis software
Measured: baseline to 28 days
EQ-5D A Standardised Patient Reported Measure of Health Status for Clinical and Economic Appraisal
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
Measured: baseline to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2011 (estimated)
- Study startMay 2011
- Primary completion19 May 2016
- Study completion13 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Raynaud's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Southern Illinois University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael W Neumeister, MD, Principal investigator, Southern Illinois University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01309802
- Sponsor's protocol ID
- NEU-SIUSOM-11-001
- Status last verified
- Dec 2018
- First submitted
- 4 Mar 2011
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: We will not be sharing data.
Publications
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.
PubMed 21134617Neumeister 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.
PubMed 19568080Sycha 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.
PubMed 15086364Van 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.
PubMed 17255677Fregene 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.
PubMed 19258141
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01309802
- Acronym / sponsor ID
- NEU-SIUSOM-11-001
- Conditions
- Raynaud's Disease
- Keywords
- botox, raynaud's, botulinum toxin, botulinum toxin A, raynaud's disease, raynaud's syndrome, raynaud's phenomenon, ischemic digits
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Southern Illinois UniversityUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- 19 May 2016 (actual)
- Study completion
- 13 Jul 2016 (actual)
- First posted
- 7 Mar 2011 (estimated)
- Results
- Posted 2 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | No intervention | –no intervention |
| onabotulinum toxin type-A | Active comparator | Drug: onabotulinum 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| onabotulinum toxin type-AAlso: BOTOX®, botulinum 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 | Drug | onabotulinum toxin type-A |
Primary outcome
Percentage of Patient Reported Pain-free Days
Time frame: baseline 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.
5 secondary outcomes
Pain Related Quality of Life
Time frame: change from baseline to 28 days
Hand Function
Time frame: baseline to 28 days
Patient Satisfaction
Time frame: baseline to 28 days
Tissue Perfusion
Time frame: baseline to 28 days
EQ-5D A Standardised Patient Reported Measure of Health Status for Clinical and Economic Appraisal
Time frame: baseline to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21134617Neumeister 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.
- Background: PubMed 19568080Neumeister 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.
- Background: PubMed 15086364Sycha 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.
- Background: PubMed 17255677Van 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.
- Background: PubMed 19258141Fregene 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.
- U.S. Food and Drug AdministrationLink provided by the sponsor.
- Drugs@FDA; U.S. Food and Drug AdministrationLink provided by the sponsor.
- Individual participant dataSharing planned: No. We will not be sharing data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael W Neumeister, MD principal investigator
Southern Illinois University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing onabotulinum toxin type-A in people with Raynaud's Disease, run by Southern Illinois University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patient Reported Pain-free Days (time frame: baseline to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01309802, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.