Botulinum Toxin in Raynaud's Phenomenon

March 2, 2024 updated by: Paul A Ghareeb, MD, Emory University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Placebo
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.
Active Comparator: 10 units of BT per digit
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.
Drug: Botulinum 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.
Active Comparator: 20 units of BT per digit
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.
Drug: Botulinum 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in finger temperature measure
Time Frame: Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Temperature of the each finger on each hand will be evaluated pre-treatment and at regular follow up intervals baseline, 4 weeks, 12 weeks, 24 weeks post injection
Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Change in 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 will be recorded on each digit prior to treatment and at the allotted follow up intervals.
Baseline, 4 weeks, 12 weeks, 24 weeks post injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Raynaud Condition Score
Time Frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
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").
Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
Changes in Visual Analog Scale (VAS) pain score
Time Frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
The visual analogue scale or visual analog 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 end-points.
Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
Changes in PROMIS Pain Interference scale
Time Frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
PROMIS Pain Interference (PROMIS-PI) scale measures the extent to which pain hinders an individual's engagement with physical, mental, cognitive, emotional, recreational, and social activities.
Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
Changes in Hand subjectivity value
Time Frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
Patients will provide ratings of their subjective hand function from 0 to 100
Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
Changes in QUICK Dash assessment
Time Frame: Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.
The Quick DASH uses 11 items to measure physical function and symptoms in people with any or multiple musculoskeletal disorders of the upper limb. It is scored in two components: the disability/symptom section (11 items, scored 1-5) and the optional high performance sport/music or work modules (four items, scored 1-5).
Performed at 4 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks. Week 16 and week 20 measurements will be performed via telephone interview.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

American Society for Surgery of the Hand

Investigators

  • Principal Investigator: Paul A Ghareeb, MD, Emory University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2022

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

October 26, 2021

First Submitted That Met QC Criteria

November 7, 2021

First Posted (Actual)

November 18, 2021

Study Record Updates

Last Update Posted (Actual)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 2, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00002359

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual de-identified participant data will be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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