Clinical trial NCT03007004: Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis
Official title: Trial to Confirm the Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Sclerosis Patients With Digital Ulcers
Keywords: Systemic aclerosis
digital ulcer
botulinum toxin
Lead sponsor: Gunma University
Sponsor class: OTHER
First posted: 2016-12-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed with SSc in diagnostic criteria (Appendix 1) by the American-European Rheumatology Association
2. Patients who have Raynaud's phenomenon from consultation, inquiries, etc. judged by Clinical responsibility (sharing) doctor
3. 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.
   * 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.
4. At the time of acquiring consent Patients over 18 years old
5. Patients for whom consent has been obtained in writing on participation of this trial

Exclusion Criteria:

1. Patients with Raynaud's phenomenon due to diseases other than SSc
2. Patients with systemic neuromuscular junction disorder (myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis etc.)
3. Patients with advanced respiratory dysfunction
4. 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
5. 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
6. Patients who received endothelin receptor antagonist within 60 days before study drug administration
7. Patients who received the following medications within 14 days prior to study drug administration

   * Argatroban hydrate injection
   * Prostaglandin E1 Injection (eg alprostadil injection)

Primary outcomes:
measure: Percentage of subjects who completely lost index ulcer 8 weeks after administration
timeFrame: 8 weeks after administration
Secondary outcomes:
measure: the percentage of subjects with complete disappearance of index ulcer at 4, 12, and 16 weeks after administration
timeFrame: at 4, 12, and 16 weeks after administration
measure: the rate of change in the number of DUs per hand
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the number of newly formed DUs
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the number of newly formed DUs per hand
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes in RP severity were assessed using Raynaud's Condition Score [RCS]
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes of investigator rating Raynaud's Condition Score [RCS]
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes in the score of pain/numbness severity assessed using the 100-mm Visual Analog Scale (VAS)
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes of the recovery of skin temperature in the finger with the index ulcer
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes in the attack duration of Raynaud's phenomenon
timeFrame: at 4, 8, 12, and 16 weeks after administration
measure: the changes in the number of attacks of Raynaud's phenomenon per day
timeFrame: at 4, 8, 12, and 16 weeks after administration
Other outcomes:
Locations:
city: Showa
country: Japan
facility: Gunma University Graduate school of Medicine
state: Gunma
Study officials:
affiliation: Gunma University
name: Sei-ichiro Motegi
role: PRINCIPAL_INVESTIGATOR
References: