SclerodermaPhase 3NCT02165111
Efficacy of Botulinum Toxin In Scleroderma-Associated Raynaud's Syndrome
A Phase 3 study testing Onabotulinumtoxin A and sterile saline solution in people with Scleroderma and Raynaud's Syndrome, run by Johns Hopkins University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleroderma, Raynaud's Syndrome
- What is being tested?
- Onabotulinumtoxin A and sterile saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Sep 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years and older
- Diagnosed with scleroderma.
- Symptoms of Raynaud's syndrome affecting both hands (not necessarily to equal extents)
- Ability to return/be available for follow-up evaluations
- Able and willing to give informed consent
- Able to speak and read in the English language.
Who cannot join
- A history of Myasthenia gravis.
- Reported allergy or hypersensitivity to any Botulinum toxin preparation.
- Active infection in either hand.
- Patients who have ever received Botulinum toxin vaccine.
- Pregnant or lactating women.
- Females unable or unwilling to maintain abstinence or use contraception for 28 days following the injections.
- Patients who have previously undergone any vascular surgery on the upper extremity, including surgical sympathectomies.
- Current use of any aminoglycoside antibiotic
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
About this study
Official title: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome
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.
Read more
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.
- Conditions
- Scleroderma, Raynaud's Syndrome
- Being tested
- Onabotulinumtoxin A, sterile saline solution
- Keywords
- Scleroderma, Systemic, Raynaud Disease, Botulinum Toxins, Type A
- Medical subject headings
- Scleroderma, Diffuse, Raynaud Disease, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Onabotulinumtoxin ADrug
Also called Botox, Botulinum toxin, Dysport
sterile saline solutionDrug
Also called Saline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Onabotulinumtoxin A |
| 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). Receives: Drug: sterile saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured pre-injection and at one month post-injection.
Secondary outcomes (5)
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.
Measured: 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: 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: 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: 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: Measured at one month post-injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2014 (estimated)
- Study startJan 2015
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SclerodermaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Allergan
- Responsible party
- Principal investigator, Scott D. Lifchez, Johns Hopkins University
- Investigators
- Scott D Lifchez, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02165111
- Sponsor's protocol ID
- NA_00087346
- Status last verified
- Oct 2016
- First submitted
- 11 Jun 2014
- Last updated
- 22 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21868066Bello 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.
PubMed 28426903
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Assessing the Therapeutic Efficacy of Botulinum Toxin In Treating Scleroderma-Associated Raynaud's Syndrome
- ClinicalTrials.gov ID
- NCT02165111
- Acronym / sponsor ID
- NA_00087346
- Conditions
- Scleroderma, Raynaud's Syndrome
- Keywords
- Scleroderma, Systemic, Raynaud Disease, Botulinum Toxins, Type A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Allergan
- Study start
- Jan 2015
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 17 Jun 2014 (estimated)
- Results
- Posted 22 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Onabotulinumtoxin A | Experimental | Drug: Onabotulinumtoxin AOne 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 | Drug: sterile saline solutionOne 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged 18 years and older
- Diagnosed with scleroderma.
- Symptoms of Raynaud's syndrome affecting both hands (not necessarily to equal extents)
- Ability to return/be available for follow-up evaluations
- Able and willing to give informed consent
Key exclusion criteria (8 listed)
- A history of Myasthenia gravis.
- Reported allergy or hypersensitivity to any Botulinum toxin preparation.
- Active infection in either hand.
- Patients who have ever received Botulinum toxin vaccine.
- Pregnant or lactating women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Onabotulinumtoxin AAlso: Botox, Botulinum toxin, Dysport | Drug | Onabotulinumtoxin A |
| sterile saline solutionAlso: Saline | Drug | Placebo |
Primary outcome
Change in Digital Blood Flow From Pre- to Post-injection.
Time frame: 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.
5 secondary outcomes
Rate of Change in Raynaud's Phenomenon Symptoms Measured With the Raynaud's Condition Score.
Time frame: Weekly rate of change over the four-month study period.
Number of Ulcers as Measure of Digital Ulcer Healing
Time frame: Measured at one month post-injection.
Assessment of Raynaud's Symptoms Severity Using the Quick-DASH Score.
Time frame: Measured at one month post-injection.
Assessment of Raynaud's Symptom Severity Using the McCabe Cold Sensitivity Score.
Time frame: Measured at one month post-injection.
Assessment of Raynaud's Symptom Severity Using the VAS for Pain.
Time frame: Measured at one month post-injection.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21868066Iorio 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.
- Derived from this study: PubMed 28426903Bello 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott D Lifchez, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Onabotulinumtoxin A and sterile saline solution in people with Scleroderma and Raynaud's Syndrome, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Digital Blood Flow From Pre- to Post-injection. (time frame: Measured pre-injection and at one month post-injection.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02165111, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2016.