Raynaud PhenomenonPhase 4NCT05125029
Botulinum Toxin in Raynaud's Phenomenon
A Phase 4 study testing Botulinum toxin in people with Raynaud Phenomenon, run by Emory University at 1 site in United States.
Trial summary
Raynaud's Phenomenon (RP) is the most common vasospastic disorder encountered by hand surgeons with an estimated prevalence of 5% in the general population. It's manifestations are broad, and can range from minor to severe. Sometimes it can be refractory to treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Raynaud Phenomenon
- What is being tested?
- Botulinum toxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2022to 15 May 2025
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older
- Patients with moderate to severe RP that is not controlled after 3 months of standard medical therapy as prescribed by a Rheumatologist, or severe RP with evidence of tissue loss.
Who cannot join
- Patients under the age of 18
- Patients who have previously undergone treatment with BT for RP within the past year
- Patients with active infection at the treatment site (active infection defined as cellulitis, purulence, fever, chills, or presence of elevated inflammatory markers, ie. WBC, ESR, CRP)
- Patients who have undergone prior digital sympathectomy surgery for RP
- Patients who have recently altered their medical regimen for RP within the past 4 weeks
- Patients with allergy or contraindication to BT injection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double Blind RCT to Evaluate the Effect of Botulinum Toxin in Raynaud Phenomenon
Raynaud's Phenomenon (RP) is the most common vasospastic disorder encountered by hand surgeons with an estimated prevalence of 5% in the general population. It's manifestations are broad, and can range from minor to severe. Sometimes it can be refractory to treatments. The goal of this study is to evaluate the efficacy of Botulinum toxin (BT) in the treatment of treatment refractory RP by objective and subjective measures.
Read the detailed description
Raynaud's Phenomenon (RP) is the most common vasospastic (i.e. conditions where small blood vessels near the surface of the skin have spasms that limit blood flow) disorder encountered by hand surgeons with an estimated prevalence of 5% in the general population. The clinical manifestations are broad, and can range from minor pain, cold sensitivity and color changes to impaired hand function, intolerable pain and tissue loss/digital ulceration. Treatment algorithms include activity modification and medical therapies. However, refractory RP can warrant surgical intervention, such as peri-arterial sympathectomy, of which has significant associated morbidity. While the exact mechanism is still being elucidated, several retrospective reviews have demonstrated efficacy of BT in the treatment of RP. Specifically, increases in post treatment perfusion have been demonstrated and clinical evidence of improvement in pain scores and tissue loss are reported. However, the literature varies in regard to injection technique (location and dose) and duration of action.
The goal of this study is to evaluate the efficacy of BT in the treatment of treatment refractory RP by objective and subjective measures. This study will perform a single-site double-blinded, randomized, placebo-controlled trial evaluating two different doses of BT (10 units and 20 units) injected into each patient's fingers of both hands versus injection of a normal saline control, given that there is currently no widely accepted standard of care for the treatment of BT. Following injection, patients will be evaluated in regular intervals to assess for impact on finger temperature, oxygenation, patient reported outcome measures (PROMs), and effect on tissue loss.
The study will take place under Emory University School of Medicine, specifically the Upper Extremity Division. Patients may also be originally seen under the Rheumatology Division and subsequently referred to the Upper Extremity Division for study participation. In total, the study aims to recruit 36 patients. There will be no outside recruitment or advertisement materials. With this research study, the study team seeks to establish a standardized injection technique and dosage for this disease and to determine duration of symptom alleviation.
- Conditions
- Raynaud Phenomenon
- Being tested
- Botulinum toxin
- Keywords
- Botulinum toxin, Raynaud Phenomenon refractory to treatment
- Medical subject headings
- Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxinDrug
Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum that prevents the release of the neurotransmitter acetylcholine from the neuromuscular junction, thereby preventing muscular contraction. Eligible subjects will be randomized 1:1:1 into three different groups: 1) placebo 2) 10 Units of BT injected per digit and 3) 20 units of BT injected per digit.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | No intervention | Prior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. |
| 10 units of BT per digit | Active comparator | Prior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. Receives: Drug: Botulinum toxin |
| 20 units of BT per digit | Active comparator | Prior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. Receives: Drug: Botulinum toxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Finger Temperature Measure
Finger temperature measure of each finger on each hand was recorded on each digit before treatment and at the allotted follow-up intervals; the average of all digits on both hands was combined and recorded as the value for each point in data collection.
Measured: Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Tissue Oximetry Measure for Each Finger
Tissue Oximetry of each finger on each hand was recorded on each digit before treatment and at the allotted follow-up intervals. The average of all digits on both hands was combined and reported.
Measured: Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Secondary outcomes (5)
Raynaud Condition Score
The Raynaud's Condition Score (RCS) is a validated outcome measure used to assess the level of difficulty experienced due to RP each day (anchored from "no difficulty" to "extreme difficulty").
Scale of 0-10 based on how patients rate any difficulty with their hands the day of assessment, a score of 0 is the minimum score and is interpreted as a best outcome (being described to patients as "no difficulty"), while a score of 10 is the maximum score and is interpreted as the worst outcome (being described to patients as "extreme difficulty")
Measured: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Visual Analog Scale (VAS) Pain Score
The visual analogue scale or visual analogue scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their level of agreement to a statement by indicating a position along a continuous line between two endpoints.VAS scores ranged from 0 (no pain) to 10 (worst imaginable pain) Higher VAS scores indicate greater pain severity Week 16 and week 20 measurements were performed via telephone interview.
Measured: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
PROMIS Pain Interference Scale
The visual analogue scale (VAS) is a psychometric response scale that can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their level of agreement to a statement by indicating a position along a continuous line between two endpoints.
Scale of 0-10, a minimum score of 0 is viewed as a favorable outcome and described to patients as having "no pain", a score of 10 is the maximum score and is viewed as an unfavorable outcome and described to patients as having "worst pain"
Measured: 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Hand Subjectivity Value
Patients provided ratings of their subjective hand function from 0 to 100. Higher ratings mean better outcomes.
Week 16 and week 20 measurements were performed via telephone interview.
Measured: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
QUICK Dash Assessment
The QuickDASH is an 11-item questionnaire that measures physical function and symptoms in individuals with one or more upper-limb musculoskeletal disorders. It includes a disability/symptom section (11 items, scored 1-5) and optional work or sport/music modules (4 items each, scored 1-5). Each response option is associated with a percentage value on a 0-100 scale: 1 (no symptoms) = 0.0, 2 (mild symptoms) = 2.3, 3 (moderate symptoms) = 4.5, 4 (severe symptoms) = 6.8, and 5 (extreme symptoms) = 9.1. After all questions are scored, the item scores are summed and divided by 100 to generate the final percentage score. Scores range from 0% to 100%, where 0% is the most favorable outcome, indicating no symptoms or limitations in physical activities, and 100% is the least favorable outcome, indicating extreme symptoms and severe limitations in physical activities. Higher scores reflect greater disability and symptom severity.
Measured: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2021
- Study start10 Feb 2022
- Primary completion15 May 2025
- Study completion15 May 2025
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.
- Other trials for Raynaud PhenomenonStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- American Society for Surgery of the Hand
- Responsible party
- Principal investigator, Paul A Ghareeb, MD, Emory University
- Investigators
- Paul A Ghareeb, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05125029
- Sponsor's protocol ID
- STUDY00002359
- Status last verified
- Jul 2026
- First submitted
- 26 Oct 2021
- Last updated
- 29 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No individual de-identified participant data will be shared
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind RCT to Evaluate the Effect of Botulinum Toxin in Raynaud Phenomenon
- ClinicalTrials.gov ID
- NCT05125029
- Acronym / sponsor ID
- STUDY00002359
- Conditions
- Raynaud Phenomenon
- Keywords
- Botulinum toxin, Raynaud Phenomenon refractory to treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- American Society for Surgery of the Hand
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- 15 May 2025 (actual)
- Study completion
- 15 May 2025 (actual)
- First posted
- 18 Nov 2021 (actual)
- Results
- Posted 29 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Raynaud's Phenomenon (RP) is the most common vasospastic disorder encountered by hand surgeons with an estimated prevalence of 5% in the general population. It's manifestations are broad, and can range from minor to severe. Sometimes it can be refractory to treatments. The goal of this study is to evaluate the efficacy of Botulinum toxin (BT) in the treatment of treatment refractory RP by objective and subjective measures.
Detailed description
Raynaud's Phenomenon (RP) is the most common vasospastic (i.e. conditions where small blood vessels near the surface of the skin have spasms that limit blood flow) disorder encountered by hand surgeons with an estimated prevalence of 5% in the general population. The clinical manifestations are broad, and can range from minor pain, cold sensitivity and color changes to impaired hand function, intolerable pain and tissue loss/digital ulceration. Treatment algorithms include activity modification and medical therapies. However, refractory RP can warrant surgical intervention, such as peri-arterial sympathectomy, of which has significant associated morbidity. While the exact mechanism is still being elucidated, several retrospective reviews have demonstrated efficacy of BT in the treatment of RP. Specifically, increases in post treatment perfusion have been demonstrated and clinical evidence of improvement in pain scores and tissue loss are reported. However, the literature varies in regard to injection technique (location and dose) and duration of action.
The goal of this study is to evaluate the efficacy of BT in the treatment of treatment refractory RP by objective and subjective measures. This study will perform a single-site double-blinded, randomized, placebo-controlled trial evaluating two different doses of BT (10 units and 20 units) injected into each patient's fingers of both hands versus injection of a normal saline control, given that there is currently no widely accepted standard of care for the treatment of BT. Following injection, patients will be evaluated in regular intervals to assess for impact on finger temperature, oxygenation, patient reported outcome measures (PROMs), and effect on tissue loss.
The study will take place under Emory University School of Medicine, specifically the Upper Extremity Division. Patients may also be originally seen under the Rheumatology Division and subsequently referred to the Upper Extremity Division for study participation. In total, the study aims to recruit 36 patients. There will be no outside recruitment or advertisement materials. With this research study, the study team seeks to establish a standardized injection technique and dosage for this disease and to determine duration of symptom alleviation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | No intervention | –Prior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. |
| 10 units of BT per digit | Active comparator | Drug: Botulinum toxinPrior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. |
| 20 units of BT per digit | Active comparator | Drug: Botulinum toxinPrior to injection, patients will wait in a temperature controlled room for 30 minutes in order to allow time for normalization of baseline digital temperature. Once a patient is randomly selected via our randomization process, BT will be reconstituted by clinic nursing staff with sterile saline per manufacturer recommendations such that the investigating hand surgeon who will be performing the injection will be sufficiently blinded. After proper cleansing of the skin with alcohol swabs, BT will be sterilely administered percutaneously via a small-gauge needle and syringe into the base of each digit by the investigating hand surgeons within the Upper Extremity Division. The volar metacarpal head will be used as a standardized anatomic landmark for injection both to lessen the probability and magnitude of risk to deep structures of the hand as well as maximize probability of proper anatomic placement of the drug. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18 or older
- Patients with moderate to severe RP that is not controlled after 3 months of standard medical therapy as prescribed by a Rheumatologist, or severe RP with evidence of tissue loss.
Key exclusion criteria (6 listed)
- Patients under the age of 18
- Patients who have previously undergone treatment with BT for RP within the past year
- Patients with active infection at the treatment site (active infection defined as cellulitis, purulence, fever, chills, or presence of elevated inflammatory markers, ie. WBC, ESR, CRP)
- Patients who have undergone prior digital sympathectomy surgery for RP
- Patients who have recently altered their medical regimen for RP within the past 4 weeks
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 |
|---|---|---|
| Botulinum toxinBotulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum that prevents the release of the neurotransmitter acetylcholine from the neuromuscular junction, thereby preventing muscular contraction. Eligible subjects will be randomized 1:1:1 into three different groups: 1) placebo 2) 10 Units of BT injected per digit and 3) 20 units of BT injected per digit. | Drug | 10 units of BT per digit, 20 units of BT per digit |
Primary outcome
Finger Temperature Measure
Time frame: Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Finger temperature measure of each finger on each hand was recorded on each digit before treatment and at the allotted follow-up intervals; the average of all digits on both hands was combined and recorded as the value for each point in data collection.
Tissue Oximetry Measure for Each Finger
Time frame: Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Tissue Oximetry of each finger on each hand was recorded on each digit before treatment and at the allotted follow-up intervals. The average of all digits on both hands was combined and reported.
5 secondary outcomes
Raynaud Condition Score
Time frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Visual Analog Scale (VAS) Pain Score
Time frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
PROMIS Pain Interference Scale
Time frame: 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Hand Subjectivity Value
Time frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
QUICK Dash Assessment
Time frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No individual de-identified participant data will be shared
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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.
Paul A Ghareeb, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Botulinum toxin in people with Raynaud Phenomenon, run by Emory 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 2 inclusion and 6 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 29 Jul 2026. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 29 Jul 2026). 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?
Finger Temperature Measure (time frame: Baseline, 4 weeks, 12 weeks, 24 weeks post injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2026.