Botulinum Toxin for Raynaud's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Paul A Ghareeb, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Emory University

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

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial aims to test if Botox can help patients with severe Raynaud's Phenomenon who don't respond to other treatments. Botox is injected into the fingers to relax muscles around blood vessels, improving blood flow and reducing symptoms like pain and tissue damage. Botox has been used primarily for treating facial wrinkles and has shown effectiveness in treating excessive underarm sweating.

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 data supports the effectiveness of the drug Botulinum Toxin for Raynaud's Disease?

Research shows that Botulinum Toxin A can improve blood flow and relieve symptoms in patients with Raynaud's phenomenon, including those with severe cases and those associated with scleroderma. Patients have reported symptom improvement and healing of ulcers after treatment, with benefits lasting up to a year. ^{1 2 3 4 5}

How is the drug Botulinum Toxin unique in treating Raynaud's Disease?

Botulinum Toxin is unique for Raynaud's Disease because it targets the vasospasm (sudden narrowing of blood vessels) directly, which is not always effectively managed by existing medications. It is administered through injections, and patients have reported symptom relief lasting up to a year, which is longer than many other treatments. ^{1 3 4 6 7}

Research Team

Paul A Ghareeb, MD

Principal Investigator

Emory University

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Botulinum Toxin (Neurotoxin)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

American Society for Surgery of the Hand

Collaborator

Trials

11

Recruited

1,100+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud's Phenomenon: A Case Series. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

The mechanism of botulinum A on Raynaud syndrome. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Botulinum toxin A treatment of Raynaud's phenomenon: a review. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Clinical and image improvement of Raynaud's phenomenon after botulinum toxin type A treatment. [2016]