Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis

NCT ID: NCT03007004

Last Updated: 2020-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-12
• Study Completion Date: 2019-05-14

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.

Conditions

Systemic Sclerosis Patients With Digital Ulcers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Botulinum toxin group

400 units in one injection site（0.2mL） Total 2000 units（1.0mL） （For both hands total 4000 units; 2.0 mL）

Group Type: EXPERIMENTAL

Botulinum toxin type B (2500 units / vial)

Intervention Type: DRUG

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 saline (control drug) group

0.2mL in one injection site

Total 1.0mL (For both hands total 2.0 mL)

Group Type: SHAM_COMPARATOR

Physiological saline

Intervention Type: DRUG

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.

Interventions

Botulinum toxin type B (2500 units / vial)

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.

Intervention Type: DRUG

Physiological saline

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.

Intervention Type: DRUG

Other Intervention Names

BTX-B (E2014, Eisai, NerBloc®)

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gunma University

OTHER

Sponsor Role: lead

Responsible Party

Sei-ichiro Motegi

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sei-ichiro Motegi

Role: PRINCIPAL_INVESTIGATOR

Gunma University

Locations

Gunma University Graduate school of Medicine

Morishita, Gunma, Japan

Countries

Japan

Other Identifiers

D2016017

Identifier Type: -

Identifier Source: org_study_id