Botulinum Toxin for Raynaud's Disease

Overseen By Anthony Karzon

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Disqualifiers: Under 18, Prior BT, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Botulinum toxin (commonly known as Botox) can aid individuals with Raynaud's Phenomenon (RP) who haven't found relief from standard treatments. RP causes fingers and toes to feel numb and cold due to limited blood flow. Participants will receive either 10 or 20 units of Botox per finger or a placebo to compare effects. Ideal candidates have moderate to severe RP that hasn't improved with other treatments for at least three months or have severe cases with tissue damage. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but it does mention that patients who have recently changed their RP treatment in the past 4 weeks are excluded. This suggests that maintaining a stable medication regimen might be important.

What is the safety track record for Botulinum Toxin?

Research has shown that botulinum toxin (BT) is usually well-tolerated for treating Raynaud's phenomenon (RP). In one study, 71.7% of patients receiving BT for RP experienced improved symptoms, indicating that most people can handle the treatment without major issues.

Another study found that a single session of BT injections into both hands reduced the number of RP episodes related to systemic sclerosis, an autoimmune disease affecting the skin and other organs. This suggests that BT is both effective and safe for use in the hands.

As this is a phase 4 trial, it is important to note that BT is already approved for other uses, such as treating muscle stiffness and reducing wrinkles. This approval indicates its safety, but individual reactions can vary. Patients should always discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Raynaud's Disease, which often involve medications like calcium channel blockers to improve blood flow, botulinum toxin offers a unique approach. Researchers are excited about botulinum toxin because it works by temporarily blocking nerve signals that cause blood vessels to constrict, providing potentially quicker relief from symptoms. Moreover, its administration via direct injection into the affected digits might offer more targeted and effective results than systemic medications. This innovative method could lead to improved management of Raynaud's symptoms, offering hope for enhanced quality of life for patients.

What evidence suggests that Botulinum Toxin might be an effective treatment for Raynaud's Disease?

Studies have shown that Botulinum toxin, often called Botox, can help manage Raynaud's Phenomenon (RP), especially when other treatments haven't worked. Research indicates that many patients notice improvement after Botox injections, though some may need additional treatments to maintain the benefits. A review of several studies found that Botox consistently improved outcomes for people with RP. In this trial, participants will receive either 10 units or 20 units of Botulinum toxin per digit, or a placebo. Side effects from Botox are usually minor and resolve on their own. Overall, strong evidence supports Botox's effectiveness in treating RP symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

Paul A Ghareeb, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe Raynaud's Phenomenon (RP) that hasn't improved after 3 months of standard treatment, or those with severe RP showing tissue loss. It excludes anyone under 18, recent changes in RP meds, past year BT treatments for RP, prior surgery for RP, or active infection/allergy at the injection site.

Inclusion Criteria

My severe Raynaud's phenomenon hasn't improved after 3 months of treatment.

Exclusion Criteria

I am under 18 years old.

I have been treated with BT for RP within the last year.

I have not changed my RP treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Botulinum toxin or placebo injections into the fingers to evaluate efficacy in treating Raynaud's Phenomenon

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in finger temperature, tissue oximetry, and various pain and function scores

24 weeks

Regular follow-up visits at baseline, 4, 12, 16, 20, and 24 weeks, with some visits conducted via telephone

What Are the Treatments Tested in This Trial?

Interventions

• Botulinum Toxin

Trial Overview The study aims to test the effectiveness of Botulinum toxin (BT) in treating Raynaud's Phenomenon that doesn't respond well to usual treatments. The focus is on both objective and subjective outcomes to see how well BT works.

How Is the Trial Designed?

Group I: 10 units of BT per digit Active Control 1 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.

Group II: Placebo Active Control 1 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.

Group III: 20 units of BT per digit Active Control 1 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.

Botulinum Toxin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Botox for:

• Facial wrinkles
• Blepharospasm
• Strabismus
• Axillary hyperhidrosis
• Migraine prophylaxis
• Overactive bladder
• Neurogenic detrusor overactivity

Approved in European Union as Botox for:

• Facial wrinkles
• Blepharospasm
• Strabismus
• Axillary hyperhidrosis
• Migraine prophylaxis
• Overactive bladder
• Neurogenic detrusor overactivity
• Spasticity

Approved in Canada as Botox for:

• Facial wrinkles
• Blepharospasm
• Strabismus
• Axillary hyperhidrosis
• Migraine prophylaxis
• Overactive bladder
• Neurogenic detrusor overactivity
• Spasticity

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

American Society for Surgery of the Hand

Collaborator

Trials

11

Recruited

1,100+

Published Research Related to This Trial

In a clinical trial involving 40 patients with scleroderma-associated Raynaud's phenomenon, local injections of botulinum toxin type A (Btx-A) showed a significant reduction in blood flow in treated hands compared to placebo at the 1-month follow-up, particularly in patients with longstanding Raynaud's and diffuse scleroderma.

Despite some improvements in clinical measures for Btx-A-treated hands, the overall findings do not strongly support its use for treating Raynaud's phenomenon in all scleroderma patients, indicating a need for further research in more specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Bello, RJ., Cooney, CM., Melamed, E., et al.[2022]

Botulinum neurotoxin type A (BoNT/A) effectively inhibits arteriole vasoconstriction in Raynaud's phenomenon by blocking the release of norepinephrine from sympathetic neurons, with increased inhibition observed at higher doses.

The mechanism of action involves the cleavage of SNAP-25, which prevents vesicle fusion and norepinephrine release, indicating that BoNT/A may work similarly to cholinergic pathways in regulating blood vessel constriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mechanism of botulinum A on Raynaud syndrome. Zhou, Y., Liu, Y., Hao, Y., et al.[2022]

In a study of 30 treatment episodes over 7½ years, Botulinum toxin A injections significantly improved symptoms and healed digital ulcers in patients with Raynaud's phenomenon who had not responded to other treatments.

The injections, primarily administered near the palmar digital neurovascular bundle at a concentration of 50 U/ml, were well tolerated, with only one case of temporary muscle weakness and no long-term adverse effects, indicating a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted high concentration botulinum toxin A injections in patients with Raynaud's phenomenon: a retrospective single-centre experience. Nagarajan, M., McArthur, P.[2021]

Abobotulinum toxin A injections were used to treat Raynaud's phenomenon in four patients, showing clinical improvement in symptoms for up to one year.

This case series suggests that abobotulinum toxin A may be an effective treatment option for patients with mild to severe Raynaud's phenomenon, especially when traditional pharmacologic treatments are not effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud's Phenomenon: A Case Series. Winter, AR., Camargo Macias, K., Kim, S., et al.[2020]

Botulinum toxin type A (BTX-A) has shown promise as a treatment for Raynaud's phenomenon, with two patients experiencing significant clinical and imaging improvements after injection.

This case report suggests that BTX-A may be a viable alternative for patients who do not respond well to traditional pharmacological therapies or sympathectomies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and image improvement of Raynaud's phenomenon after botulinum toxin type A treatment. Zhao, H., Lian, Y.[2016]

A review of 11 studies involving 125 patients found that while botulinum toxin A shows potential for managing Raynaud's phenomenon, the overall evidence for its efficacy is low to moderate.

Current findings are insufficient to conclusively determine the effectiveness of botulinum toxin A for pain reduction and healing of digital ulcers in Raynaud's phenomenon, highlighting the need for more rigorous randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review. Żebryk, P., Puszczewicz, MJ.[2022]

Botulinum toxin A has shown promising results in treating Raynaud's phenomenon, with five studies reporting improvements in patient pain and a reduction in soft tissue ulceration after injections ranging from 10 to 100 units in the fingers and hands.

Despite the positive outcomes, the studies had limitations such as lack of controls and variability in disease severity and dosing, indicating a need for larger, more controlled trials to better understand its efficacy and mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin A treatment of Raynaud's phenomenon: a review. Iorio, ML., Masden, DL., Higgins, JP.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11598569/

Botulinum Toxin for the Treatment of Raynaud's Conditions ... A critical analysis of published studies to date demonstrates varied clinical efficacy of BTX-A in Raynaud's conditions based on patient- ...

2. jaad.org jaad.org/article/S0190-9622(24)02890-1/fulltext

Botulinum toxin for Raynaud's phenomenon: A decade ... After a median of 12 months, 86.2% required to repeat BT administration and 92% of them also experienced improvement with subsequent doses.

3. cda-amc.ca cda-amc.ca/sites/default/files/rr/2019/RB1325%20Botox%20for%20Raynauds%20Disease%20Final.pdf

Botulinum Toxin for Raynaud's Disease One systematic review, two randomized controlled trials, and five non-randomized studies were identified regarding clinical effectiveness of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0049017211002009

Botulinum Toxin A Treatment of Raynaud's Phenomenon The studies have many limitations (lack of controls, variable severity of disease, variability of dosing) but all report favorable clinical results. All showed ...

5. researchexperts.utmb.edu researchexperts.utmb.edu/en/publications/the-use-of-botulinum-toxin-in-raynaud-phenomenon-a-comprehensive-

The Use of Botulinum Toxin in Raynaud Phenomenon Conclusions Botulinum toxin treatment for RP is effective. Complications are minor and self-limiting. AB - Background Raynaud phenomenon (RP) is ...

6. jaad.org jaad.org/article/S0190-9622(24)03330-9/fulltext

Comment on “Botulinum toxin for Raynaud's phenomenon In this retrospective uncontrolled study, 46 patients were treated by botulinum toxin for a Raynaud's phenomenon (RP), and 71.7% of them ...

7. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.42342

Efficacy and Safety of Botulinum Toxin in Adults with ... A single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis–associated Raynaud's ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01309802

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