Systemic Sclerosis Patients With Digital UlcersPhase 2NCT03007004
Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis
A Phase 2 study testing Botulinum toxin type B (2500 units / vial) and Physiological saline in people with Systemic Sclerosis Patients With Digital Ulcers, run by Gunma University at 1 site in Japan.
Trial summary
Efficacy and safety of local infusion of botulinum toxin type B in patients with systemic sclerosis (SSc) with digital ulcer is evaluated by a randomized, double-blind study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis Patients With Digital Ulcers
- What is being tested?
- Botulinum toxin type B (2500 units / vial) and Physiological saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteJapan
- Study dates
- 12 Dec 2016to 14 May 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Patients diagnosed with SSc in diagnostic criteria (Appendix 1) by the American-European Rheumatology Association
- Patients who have Raynaud's phenomenon from consultation, inquiries, etc. judged by Clinical responsibility (sharing) doctor
- Patients with digital ulcer at acquiring consent The criteria for digital ulcers are as follows.
- It is a peripheral ulcer from the proximal interphalangeal joint and the thumb interphalangeal joint (including the interphalangeal joint).
- The continuity of coating by the epithelium has been lost and there is a depth that is visible to the eye. Incidentally, when exposed, cases covered with eschar or necrotic tissue are also included.
- If the exposure is not clearly recognized (crusted or covered with necrotic tissue), the investigational responsibility (shared) doctor can judge that the epidermis and the dermis are missing.
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- It should not be the paronychia、crack、digital pitting scars.
- It should not be attached to the projection of the calcification.
- Size: The maximum diameter (major axis) is 0.5 cm or more.
- Bones, tendons and joints are not exposed.
- It is not accompanied by obvious infection findings.
- At the time of acquiring consent Patients over 18 years old
- Patients for whom consent has been obtained in writing on participation of this trial
Who cannot join
- Patients with Raynaud's phenomenon due to diseases other than SSc
- Patients with systemic neuromuscular junction disorder (myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis etc.)
- Patients with advanced respiratory dysfunction
- Patients with a history of hypersensitivity to components of botulinum toxin type B (botulinum toxin type B, human serum albumin, succinate buffer) or other botulinum toxin
- Patients who received botulinum toxin formulation within 4 months before study drug administration or who have continued efficacy of botulinum toxin at the time of administration of investigational drug even when administered more than 4 months ago
- Patients who received endothelin receptor antagonist within 60 days before study drug administration
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- Patients who received the following medications within 14 days prior to study drug administration
- Argatroban hydrate injection
- Prostaglandin E1 Injection (eg alprostadil injection)
Trial locations and contacts
1 site in 1 country.
Japan1 site
Gunma University Graduate school of Medicine
Morishita, Gunma, 371-8511
About this study
Official title: Trial to Confirm the Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis
Efficacy and safety of local infusion of botulinum toxin type B in patients with systemic sclerosis (SSc) with digital ulcer is evaluated by a randomized, double-blind study.
Read the detailed description
To assess the efficacy and safety of local injection of botulinum toxin type B (BTX-B) against digital ulcers (DUs) and Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc).
In a randomized, double-blind, placebo-controlled, investigator-initiated clinical trial (phase II), 10 patients with SSc and RP-related DUs were randomly and evenly assigned to a placebo control group or treatment group taking BTX-B injections. The degree of improvement in DU, change in size, number of new DUs, improvement in symptoms of RP, and adverse events were recorded.
- Being tested
- Botulinum toxin type B (2500 units / vial), Physiological saline
- Keywords
- Systemic aclerosis, digital ulcer, botulinum toxin
- Medical subject headings
- digital ulcers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum toxin type B (2500 units / vial)Drug
Also called BTX-B (E2014, Eisai, NerBloc®)
BTX-B (E2014, Eisai, NerBloc®) was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with 400 U (0.2 ml) of BTX-B. In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of BTX-B (200 units; 0.1 ml). A total of 2000 U (1.0 ml) of BTX-B was injected into one hand. Injections were performed using a 30-gauge needle.
Physiological salineDrug
Saline solution was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with saline (0.2 ml). In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of saline (0.1 ml). A total of 1.0 ml of saline was injected into one hand. Injections were performed using a 30-gauge needle.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin group | Experimental | 400 units in one injection site（0.2mL） Total 2000 units（1.0mL） （For both hands total 4000 units; 2.0 mL） Receives: Drug: Botulinum toxin type B (2500 units / vial) |
| Physiological saline (control drug) group | Sham comparator | 0.2mL in one injection site
Total 1.0mL (For both hands total 2.0 mL) Receives: Drug: Physiological saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects who completely lost index ulcer 8 weeks after administration
The primary end point was the percentage of subjects with complete disappearance of index ulcer 8 weeks after administration. The index ulcer was defined as the largest DUs in the hand. The size of DU was measured as both the longest diameter of the ulcer and the diameter perpendicular to the center of the ulcer's diameter. Complete disappearance is defined as the disappearance of the area of the ulcer that has become epithelialized and covered by the epidermis from the periphery of the ulcer and continued coverage of the ulcer surface area that has been restored.
Measured: 8 weeks after administration
Secondary outcomes (10)
the percentage of subjects with complete disappearance of index ulcer at 4, 12, and 16 weeks after administration
the percentage of subjects with complete disappearance of index ulcer at 4, 12, and 16 weeks after administration
Measured: at 4, 12, and 16 weeks after administration
the rate of change in the number of DUs per hand
the rate of change in the number of DUs per hand
Measured: at 4, 8, 12, and 16 weeks after administration
the number of newly formed DUs
the number of newly formed DUs
Measured: at 4, 8, 12, and 16 weeks after administration
the number of newly formed DUs per hand
the number of newly formed DUs per hand
Measured: at 4, 8, 12, and 16 weeks after administration
the changes in RP severity were assessed using Raynaud's Condition Score [RCS]
the changes in RP severity were assessed using Raynaud's Condition Score [RCS]. RCS is a daily self-assessment of RP activity using a 0-10 ordinal scale. RCS incorporates the cumulative daily frequency, duration, severity, and effect of RP attacks. RCS was averaged over a 7-day period preceding the baseline and each subsequent visit.
Measured: at 4, 8, 12, and 16 weeks after administration
the changes of investigator rating Raynaud's Condition Score [RCS]
the changes of investigator rating Raynaud's Condition Score [RCS]. Investigator rating RCS was also assessed by the investigator (SM).
Measured: at 4, 8, 12, and 16 weeks after administration
the changes in the score of pain/numbness severity assessed using the 100-mm Visual Analog Scale (VAS)
Pain/numbness severity was assessed using the 100-mm Visual Analog Scale (VAS). Pain/numbness severity was assessed using the 100-mm Visual Analog Scale (VAS) (range 0-100; 0 refers to no pain/numbness, and 100 refers to worst imaginable pain/numbness)
Measured: at 4, 8, 12, and 16 weeks after administration
the changes of the recovery of skin temperature in the finger with the index ulcer
the skin temperature of the finger was measured just after and 10 minutes after an ice-bath immersion
Measured: at 4, 8, 12, and 16 weeks after administration
the changes in the attack duration of Raynaud's phenomenon
the changes in the attack duration of Raynaud's phenomenon
Measured: at 4, 8, 12, and 16 weeks after administration
the changes in the number of attacks of Raynaud's phenomenon per day
the number of attacks of Raynaud's phenomenon per day was assessed for 7days
Measured: at 4, 8, 12, and 16 weeks after administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2016 (estimated)
- Study start12 Dec 2016
- Primary completion14 May 2019
- Study completion14 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Sclerosis Patients With Digital UlcersStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gunma University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sei-ichiro Motegi, Gunma University
- Investigators
- Sei-ichiro Motegi, Principal investigator, Gunma University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03007004
- Sponsor's protocol ID
- D2016017
- Status last verified
- May 2020
- First submitted
- 28 Dec 2016
- Last updated
- 14 May 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial to Confirm the Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT03007004
- Acronym / sponsor ID
- D2016017
- Keywords
- Systemic aclerosis, digital ulcer, botulinum toxin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Gunma UniversityUniversity, hospital or other
- Study start
- 12 Dec 2016 (actual)
- Primary completion
- 14 May 2019 (actual)
- Study completion
- 14 May 2019 (actual)
- First posted
- 30 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy and safety of local infusion of botulinum toxin type B in patients with systemic sclerosis (SSc) with digital ulcer is evaluated by a randomized, double-blind study.
Detailed description
To assess the efficacy and safety of local injection of botulinum toxin type B (BTX-B) against digital ulcers (DUs) and Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc).
In a randomized, double-blind, placebo-controlled, investigator-initiated clinical trial (phase II), 10 patients with SSc and RP-related DUs were randomly and evenly assigned to a placebo control group or treatment group taking BTX-B injections. The degree of improvement in DU, change in size, number of new DUs, improvement in symptoms of RP, and adverse events were recorded.
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 |
|---|---|---|
| Botulinum toxin group | Experimental | Drug: Botulinum toxin type B (2500 units / vial)400 units in one injection site（0.2mL） Total 2000 units（1.0mL） （For both hands total 4000 units; 2.0 mL） |
| Physiological saline (control drug) group | Sham comparator | Drug: Physiological saline0.2mL in one injection site Total 1.0mL (For both hands total 2.0 mL) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients diagnosed with SSc in diagnostic criteria (Appendix 1) by the American-European Rheumatology Association
- Patients who have Raynaud's phenomenon from consultation, inquiries, etc. judged by Clinical responsibility (sharing) doctor
- Patients with digital ulcer at acquiring consent The criteria for digital ulcers are as follows.
- At the time of acquiring consent Patients over 18 years old
- Patients for whom consent has been obtained in writing on participation of this trial
Key exclusion criteria (9 listed)
- Patients with Raynaud's phenomenon due to diseases other than SSc
- Patients with systemic neuromuscular junction disorder (myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis etc.)
- Patients with advanced respiratory dysfunction
- Patients with a history of hypersensitivity to components of botulinum toxin type B (botulinum toxin type B, human serum albumin, succinate buffer) or other botulinum toxin
- Patients who received botulinum toxin formulation within 4 months before study drug administration or who have continued efficacy of botulinum toxin at the time of administration of investigational drug even when administered more than 4 months ago
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 |
|---|---|---|
| Botulinum toxin type B (2500 units / vial)Also: BTX-B (E2014, Eisai, NerBloc®)BTX-B (E2014, Eisai, NerBloc®) was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with 400 U (0.2 ml) of BTX-B. In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of BTX-B (200 units; 0.1 ml). A total of 2000 U (1.0 ml) of BTX-B was injected into one hand. Injections were performed using a 30-gauge needle. | Drug | Botulinum toxin group |
| Physiological salineSaline solution was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with saline (0.2 ml). In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of saline (0.1 ml). A total of 1.0 ml of saline was injected into one hand. Injections were performed using a 30-gauge needle. | Drug | Physiological saline (control drug) group |
Primary outcome
Percentage of subjects who completely lost index ulcer 8 weeks after administration
Time frame: 8 weeks after administration
The primary end point was the percentage of subjects with complete disappearance of index ulcer 8 weeks after administration. The index ulcer was defined as the largest DUs in the hand. The size of DU was measured as both the longest diameter of the ulcer and the diameter perpendicular to the center of the ulcer's diameter. Complete disappearance is defined as the disappearance of the area of the ulcer that has become epithelialized and covered by the epidermis from the periphery of the ulcer and continued coverage of the ulcer surface area that has been restored.
10 secondary outcomes
the percentage of subjects with complete disappearance of index ulcer at 4, 12, and 16 weeks after administration
Time frame: at 4, 12, and 16 weeks after administration
the rate of change in the number of DUs per hand
Time frame: at 4, 8, 12, and 16 weeks after administration
the number of newly formed DUs
Time frame: at 4, 8, 12, and 16 weeks after administration
the number of newly formed DUs per hand
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes in RP severity were assessed using Raynaud's Condition Score [RCS]
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes of investigator rating Raynaud's Condition Score [RCS]
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes in the score of pain/numbness severity assessed using the 100-mm Visual Analog Scale (VAS)
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes of the recovery of skin temperature in the finger with the index ulcer
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes in the attack duration of Raynaud's phenomenon
Time frame: at 4, 8, 12, and 16 weeks after administration
the changes in the number of attacks of Raynaud's phenomenon per day
Time frame: at 4, 8, 12, and 16 weeks after administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2020.
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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.
Sei-ichiro Motegi principal investigator
Gunma University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Botulinum toxin type B (2500 units / vial) and Physiological saline in people with Systemic Sclerosis Patients With Digital Ulcers, run by Gunma University at 1 site in Japan.
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 13 inclusion and 9 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 14 May 2020. 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 Japan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of subjects who completely lost index ulcer 8 weeks after administration (time frame: 8 weeks after administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2020.