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Botulinum Toxin in Raynaud's Phenomenon

Primary Purpose

Raynaud Phenomenon

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Botulinum toxin
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Raynaud Phenomenon focused on measuring Botulinum toxin, Raynaud Phenomenon refractory to treatment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Emory University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Active Comparator

Active Comparator

Arm Label

Placebo

10 units of BT per digit

20 units of BT per digit

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in finger temperature measure
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
Change in tissue Oximetry measure for each finger
Tissue Oximetry of each finger on each hand will be recorded on each digit prior to treatment and at the allotted follow up intervals.

Secondary Outcome Measures

Changes in 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").
Changes in Visual Analog Scale (VAS) pain score
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.
Changes in PROMIS Pain Interference scale
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.
Changes in Hand subjectivity value
Patients will provide ratings of their subjective hand function from 0 to 100
Changes in QUICK Dash assessment
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).

Full Information

First Posted
October 26, 2021
Last Updated
February 27, 2023
Sponsor
Emory University
Collaborators
American Society for Surgery of the Hand
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1. Study Identification

Unique Protocol Identification Number
NCT05125029
Brief Title
Botulinum Toxin in Raynaud's Phenomenon
Official Title
Double Blind RCT to Evaluate the Effect of Botulinum Toxin in Raynaud Phenomenon
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
American Society for Surgery of the Hand

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Raynaud Phenomenon
Keywords
Botulinum toxin, Raynaud Phenomenon refractory to treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
No Intervention
Arm Description
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.
Arm Title
10 units of BT per digit
Arm Type
Active Comparator
Arm Description
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.
Arm Title
20 units of BT per digit
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in finger temperature measure
Description
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
Time Frame
Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Title
Change in tissue Oximetry measure for each finger
Description
Tissue Oximetry of each finger on each hand will be recorded on each digit prior to treatment and at the allotted follow up intervals.
Time Frame
Baseline, 4 weeks, 12 weeks, 24 weeks post injection
Secondary Outcome Measure Information:
Title
Changes in Raynaud Condition Score
Description
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").
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.
Title
Changes in Visual Analog Scale (VAS) pain score
Description
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.
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.
Title
Changes in PROMIS Pain Interference scale
Description
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.
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.
Title
Changes in Hand subjectivity value
Description
Patients will provide ratings of their subjective hand function from 0 to 100
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.
Title
Changes in QUICK Dash assessment
Description
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).
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paul A Ghareeb, MD
Phone
404-686-8143
Email
paul.ghareeb@emory.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Anthony Karzon
Email
akarzon@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul A Ghareeb, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Dawes
Email
alexander.dawes@emory.edu

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No individual de-identified participant data will be shared

Learn more about this trial

Botulinum Toxin in Raynaud's Phenomenon

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