Raynaud Phenomenon
Conditions
Keywords
Botulinum toxin, Raynaud Phenomenon refractory to treatment
Brief 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. 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.
Interventions
DRUGBotulinum toxin
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.
Sponsors
Emory University
American Society for Surgery of the Hand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Finger Temperature Measure | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Raynaud Condition Score | Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. | 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") |
| Visual Analog Scale (VAS) Pain Score | Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. | 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. |
| PROMIS Pain Interference Scale | 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. | 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" |
| Hand Subjectivity Value | Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. | 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. |
| QUICK Dash Assessment | Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPaul A Ghareeb, MD
Emory University
Participant flow
Recruitment details
A total of 24 participants were recruited from Emory University Hospital. Participant enrollment began February 10, 2022, and all follow-up assessments were completed by May 15, 2025
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 2 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
None listed