Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02165111
Recruitment Status : Completed
First Posted : June 17, 2014
Results First Posted : December 22, 2016
Last Update Posted : December 22, 2016
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Scott D. Lifchez, Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Scleroderma
Raynaud's Syndrome
Interventions Drug: Onabotulinumtoxin A
Drug: sterile saline solution
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

Period Title: Overall Study
Number of participants Number of units (Hands) Number of participants Number of units (Hands)
Started 40 40 40 40
Completed 40 40 40 40
Not Completed 0 0 0 0
Arm/Group Title Onabotulinumtoxin A Placebo Total
Hide Arm/Group Description

One hand of each patient was be randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Total of all reporting groups
Overall Number of Baseline Participants 40 40 40
Overall Number of Units Analyzed
Type of Units Analyzed: Hands
40 40 80
Hide Baseline Analysis Population Description
This trial was designed as a within-participant study where one of the 40 participants' hands was randomized to receive Onabotulinumtoxin A and the other to receive placebo. Each participant thus contributed two hands to the total number of units analyzed.
Age, Categorical  
Count of Units
Unit of measure:  Hands
Number Analyzed 40 Hands 40 Hands 80 Hands
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  87.5%
35
  87.5%
70
  87.5%
>=65 years
5
  12.5%
5
  12.5%
10
  12.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 40 participants 40 participants
51.9  (12.33) 51.9  (12.33) 51.9  (12.33)
Gender  
Count of Units
Unit of measure:  Hands
Number Analyzed 40 Hands 40 Hands 80 Hands
Female
9
  22.5%
9
  22.5%
18
  22.5%
Male
31
  77.5%
31
  77.5%
62
  77.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 40 Hands 40 Hands 80 Hands
40 40 40
Laser Doppler Imaging Blood Flow   [1] 
Mean (Standard Deviation)
Unit of measure:  LDI flux units
Number Analyzed 40 Hands 40 Hands 80 Hands
398.24  (190.27) 395.65  (189.17) 396.94  (188.52)
[1]
Measure Description: Laser Doppler Imaging measures blood flow using a low-energy laser beam that quantifies the Doppler effect between red blood cells and a scanner to determine blood flow speed, allowing non-invasive, objective measurement of superficial cutaneous blood flow.
1.Primary Outcome
Title Change in Digital Blood Flow From Pre- to Post-injection.
Hide Description The primary outcome measure is change in blood flow to the fingers, from a pre-injection baseline to post-injection follow-up visit as measured by non-invasive laser Doppler imaging.
Time Frame Measured pre-injection and at one month post-injection.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (95% Confidence Interval)
Unit of Measure: Blood flow, measured in LDI flux units,
-36.19
(-78.49 to 6.12)
-6.10
(-46.28 to 34.07)
2.Secondary Outcome
Title Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
Hide Description

Raynaud's Condition Score is a patient-reported, validated outcomes scale that measures the severity of Raynaud's phenomenon on a scale of 0 ("No difficulty") to 10 ("Extreme difficulty"), where higher values represent a worse outcome.

Data from each weekly report were combined using a statistical model (generalized linear population-average model) to calculate a weekly rate of change for each participant's hand, where a negative value represents a improvement over time and a positive value represents worsening over time.

Time Frame Weekly rate of change over the four-month study period.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient were randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient were randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (95% Confidence Interval)
Unit of Measure: change in RCS/week
-0.18
(-0.22 to -0.13)
-0.14
(-0.18 to -0.11)
3.Secondary Outcome
Title Number of Ulcers as Measure of Digital Ulcer Healing
Hide Description A secondary outcome of this study is the number of digital ulcers as determined by clinical examination. Mean number of ulcers was calculated as total number of ulcers / total number of hands in each group.
Time Frame Measured at one month post-injection.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: Number of ulcers
0.45  (0.90) 0.53  (0.93)
4.Secondary Outcome
Title Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
Hide Description A secondary outcome of this study is severity of Raynaud's symptoms as measured by the self-reported Quick-DASH score. The Quick-DASH scores measures the degree of hand and upper extremity function on a scale of 0 (not limited) to 100 (severely limited) where a higher value represents a worse outcome.
Time Frame Measured at one month post-injection.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: Units on a scale
26.96  (20.68) 29.11  (23.80)
5.Secondary Outcome
Title Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
Hide Description A secondary outcome of this study is the patient-reported sensitivity to coldness as measured by the McCabe Cold Sensitivity score. Patients' answers on this validated instrument are scored on a scale from 0 (no sensitivity) to 400 (extreme sensitivity), where a higher number represents a worse outcome.
Time Frame Measured at one month post-injection.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: Units on a scale
185.31  (74.19) 187.19  (86.76)
6.Secondary Outcome
Title Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
Hide Description A secondary outcome of this study is pain as measured by the validated visual-analog scale (VAS) for pain. The VAS pain instrument measures pain on a scale from 0 cm (no pain) to 10 cm (extreme pain)
Time Frame Measured at one month post-injection.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description:

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

Overall Number of Participants Analyzed 40 40
Mean (Standard Deviation)
Unit of Measure: centimeters measured on a visual scale
2.68  (2.57) 3.05  (2.77)
Time Frame 4 months
Adverse Event Reporting Description Participants were asked about adverse events during a safety call at 1 week post-injection and in-person visits at 1-month and 4-months post-injection visits.
 
Arm/Group Title Onabotulinumtoxin A Placebo
Hide Arm/Group Description

One hand of each patient was randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (10 units each=0.5mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (5 units each= 0.25mL each). Total treatment dose of Botulinum Toxin A will not exceed 50 units per hand.

Onabotulinumtoxin A

One hand of each patient was randomly selected for injection of sterile saline solution (placebo).

Injections were performed using a 30 gauge insulin syringe through the dorsal surface in seven locations: adjacent to the 2nd, 3rd, and 4th common digital arteries through the web spaces (0.5 mL each), and the radial side of the index finger metacarpal head, the ulnar side of the small finger metacarpal head, and each side of the thumb metacarpal head (0.25 mL each).

sterile saline solution

All-Cause Mortality
Onabotulinumtoxin A Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Onabotulinumtoxin A Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/40 (0.00%)      0/40 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Onabotulinumtoxin A Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/40 (5.00%)      0/40 (0.00%)    
Injury, poisoning and procedural complications     
Intrinsic muscle weakness   2/40 (5.00%)  2 0/40 (0.00%)  0
Indicates events were collected by systematic assessment
Multi-level data prevents conclusions from being drawn from aggregate data alone. High degree of variability of the results suggests a heterogeneous group of scleroderma patients. Screening methods and no dose escalation may explain negative findings
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Ricardo J. Bello
Organization: Johns Hopkins University
Phone: 4109557566
EMail: rbello@jhmi.edu
Layout table for additonal information
Responsible Party: Scott D. Lifchez, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02165111    
Other Study ID Numbers: NA_00087346
First Submitted: June 11, 2014
First Posted: June 17, 2014
Results First Submitted: September 1, 2016
Results First Posted: December 22, 2016
Last Update Posted: December 22, 2016