Trial Outcomes & Findings for Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome (NCT NCT02165111)
NCT ID: NCT02165111
Last Updated: 2016-12-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
40 participants
Primary outcome timeframe
Measured pre-injection and at one month post-injection.
Results posted on
2016-12-22
Participant Flow
Unit of analysis: Hands
Participant milestones
| Measure |
Onabotulinumtoxin A
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.
|
Placebo
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).
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|---|---|---|
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Overall Study
STARTED
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40 40
|
40 40
|
|
Overall Study
COMPLETED
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40 40
|
40 40
|
|
Overall Study
NOT COMPLETED
|
0 0
|
0 0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome
Baseline characteristics by cohort
| Measure |
Onabotulinumtoxin A
n=40 Hands
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
|
Placebo
n=40 Hands
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
n=80 Hands
Total of all reporting groups
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|---|---|---|---|
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Age, Categorical
<=18 years
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0 Hands
n=40 Hands
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0 Hands
n=40 Hands
|
0 Hands
n=80 Hands
|
|
Age, Categorical
Between 18 and 65 years
|
35 Hands
n=40 Hands
|
35 Hands
n=40 Hands
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70 Hands
n=80 Hands
|
|
Age, Categorical
>=65 years
|
5 Hands
n=40 Hands
|
5 Hands
n=40 Hands
|
10 Hands
n=80 Hands
|
|
Age, Continuous
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51.9 years
STANDARD_DEVIATION 12.33 • n=5 Participants
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51.9 years
STANDARD_DEVIATION 12.33 • n=7 Participants
|
51.9 years
STANDARD_DEVIATION 12.33 • n=5 Participants
|
|
Gender
Female
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9 Hands
n=40 Hands
|
9 Hands
n=40 Hands
|
18 Hands
n=80 Hands
|
|
Gender
Male
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31 Hands
n=40 Hands
|
31 Hands
n=40 Hands
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62 Hands
n=80 Hands
|
|
Region of Enrollment
United States
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40 participants
n=40 Hands
|
40 participants
n=40 Hands
|
40 participants
n=80 Hands
|
|
Laser Doppler Imaging Blood Flow
|
398.24 LDI flux units
STANDARD_DEVIATION 190.27 • n=40 Hands
|
395.65 LDI flux units
STANDARD_DEVIATION 189.17 • n=40 Hands
|
396.94 LDI flux units
STANDARD_DEVIATION 188.52 • n=80 Hands
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PRIMARY outcome
Timeframe: Measured pre-injection and at one month post-injection.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.
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Change in Digital Blood Flow From Pre- to Post-injection.
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-36.19 Blood flow, measured in LDI flux units,
Interval -78.49 to 6.12
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-6.10 Blood flow, measured in LDI flux units,
Interval -46.28 to 34.07
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SECONDARY outcome
Timeframe: Weekly rate of change over the four-month study period.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.
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
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-0.18 change in RCS/week
Interval -0.22 to -0.13
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-0.14 change in RCS/week
Interval -0.18 to -0.11
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SECONDARY outcome
Timeframe: Measured at one month post-injection.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.
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Number of Ulcers as Measure of Digital Ulcer Healing
|
0.45 Number of ulcers
Standard Deviation 0.90
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0.53 Number of ulcers
Standard Deviation 0.93
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SECONDARY outcome
Timeframe: Measured at one month post-injection.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.
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
|
26.96 Units on a scale
Standard Deviation 20.68
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29.11 Units on a scale
Standard Deviation 23.80
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SECONDARY outcome
Timeframe: Measured at one month post-injection.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.
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
|
185.31 Units on a scale
Standard Deviation 74.19
|
187.19 Units on a scale
Standard Deviation 86.76
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SECONDARY outcome
Timeframe: Measured at one month post-injection.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)
Outcome measures
| Measure |
Onabotulinumtoxin A
n=40 Participants
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
|
Placebo
n=40 Participants
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
|
|---|---|---|
|
Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
|
2.68 centimeters measured on a visual scale
Standard Deviation 2.57
|
3.05 centimeters measured on a visual scale
Standard Deviation 2.77
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Adverse Events
Onabotulinumtoxin A
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Onabotulinumtoxin A
n=40 participants at risk
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
|
Placebo
n=40 participants at risk
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
|
|---|---|---|
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Injury, poisoning and procedural complications
Intrinsic muscle weakness
|
5.0%
2/40 • Number of events 2 • 4 months
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.
|
0.00%
0/40 • 4 months
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.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place