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| Name | Class |
|---|---|
| Allergan | INDUSTRY |
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This is a randomized, double-blinded, clinical trial assessing the therapeutic efficacy of Botulinum toxin A (Onabotulinumtoxin A) in treating scleroderma-associated Raynaud's syndrome. Each patient will undergo injection with a treatment dose of Botulinum toxin A in one randomly-selected hand, and the contralateral hand will be injected with sterile saline (placebo) to serve as a control.
Study participants at the first study visit will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging to assess blood flow. After this initial assessment, the patients will undergo peri-arterial injection of Botulinum toxin A in one hand, and of sterile saline solution (placebo) in the other, in a randomized, blinded manner.
Patient will report the severity of their Raynaud's symptoms weekly over the four month study period. At one month post-injection, the patient will complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging. At four months post-injection, the patient will again complete study questionnaires, their hands will be assessed clinically for digital ulceration, and their hands will undergo non-invasive laser Doppler imaging. In addition, patient will be given the option of one week post-injection visit, at which point the same assessment will be performed.
At the conclusion of the study, unblinding will occur.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Onabotulinumtoxin A | Experimental | One hand of each patient will be randomly selected for injection of Botulinum Toxin A (Onabotulinumtoxin A, 20 units/mL). Injections are 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 | Placebo Comparator | One hand of each patient will be randomly selected for injection of sterile saline solution (placebo). Injections are 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Onabotulinumtoxin A | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Digital Blood Flow From Pre- to 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. | Measured pre-injection and at one month post-injection. |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score. | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott D Lifchez, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Bayview Medical Center | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21868066 | Background | Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud's phenomenon: a review. Semin Arthritis Rheum. 2012 Feb;41(4):599-603. doi: 10.1016/j.semarthrit.2011.07.006. Epub 2011 Aug 24. | |
| 28426903 | Derived | Bello RJ, Cooney CM, Melamed E, Follmar K, Yenokyan G, Leatherman G, Shah AA, Wigley FM, Hummers LK, Lifchez SD. The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Arthritis Rheumatol. 2017 Aug;69(8):1661-1669. doi: 10.1002/art.40123. Epub 2017 Jun 26. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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.
| ID | Title | Description |
|---|---|---|
| BG000 | Onabotulinumtoxin A | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Units |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Digital Blood Flow From Pre- to 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. | Posted | Mean | 95% Confidence Interval | Blood flow, measured in LDI flux units, | Measured pre-injection and at one month post-injection. |
|
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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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Onabotulinumtoxin A |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intrinsic muscle weakness | Injury, poisoning and procedural complications | 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
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ricardo J. Bello | Johns Hopkins University | 4109557566 | rbello@jhmi.edu |
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| ID | Term |
|---|---|
| D045743 | Scleroderma, Diffuse |
| D011928 | Raynaud Disease |
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
| D000090122 | Livedoid Vasculopathy |
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| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| D001905 | Botulinum Toxins |
| C542869 | abobotulinumtoxinA |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
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| sterile saline solution |
| Drug |
|
|
| Weekly rate of change over the four-month study period. |
| Number of Ulcers as Measure of Digital Ulcer Healing | 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. | Measured at one month post-injection. |
| Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score. | 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. | Measured at one month post-injection. |
| Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score. | 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. | Measured at one month post-injection. |
| Assessment of Raynaud's Symptom Severity Using the VAS for Pain. | 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) | Measured at one month post-injection. |
| BG001 | 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). sterile saline solution |
| BG002 | Total | Total of all reporting groups |
| Hands |
|
| Hands |
| Hands |
|
| Age, Continuous | Mean | Standard Deviation | years | Participants |
|
| Gender | Count of Units | Hands | Hands |
|
| Region of Enrollment | Number | participants | Hands |
|
| Laser Doppler Imaging Blood Flow | 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. | Mean | Standard Deviation | LDI flux units | Hands |
|
| OG001 | 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). sterile saline solution |
|
|
| Secondary | Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score. | 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. | Posted | Mean | 95% Confidence Interval | change in RCS/week | Weekly rate of change over the four-month study period. |
|
|
|
| Secondary | Number of Ulcers as Measure of Digital Ulcer Healing | 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. | Posted | Mean | Standard Deviation | Number of ulcers | Measured at one month post-injection. |
|
|
|
| Secondary | Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score. | 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. | Posted | Mean | Standard Deviation | Units on a scale | Measured at one month post-injection. |
|
|
|
| Secondary | Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score. | 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. | Posted | Mean | Standard Deviation | Units on a scale | Measured at one month post-injection. |
|
|
|
| Secondary | Assessment of Raynaud's Symptom Severity Using the VAS for Pain. | 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) | Posted | Mean | Standard Deviation | centimeters measured on a visual scale | Measured at one month post-injection. |
|
|
|
| 0 |
| 40 |
| 2 |
| 40 |
| EG001 | 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). sterile saline solution | 0 | 40 | 0 | 40 |
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| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |