Efficacy of Botulinum Toxin A in Adult Subjects With Raynaud Phenomenon Secondary to Systemic Sclerosis

NCT03717961 | Completed Phase 3

• 1 other identifier: P170904J
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess whether or not a single injection schedule of botulinum toxin A (BTX-A) in both hands improves Raynaud phenomenon (RP) secondary to systemic sclerosis (SSc) better than a placebo at 4, 12 and 24 weeks after the treatment. This study's hypothesis is that the number of RP attacks per week from baseline to 4 weeks after treatment is significantly lower in the group treated with BTX-A than in the control group treated by the placebo. Furthermore, BTX-A in both hands is expected to improve both symptomatic (attack frequency, digital ulcer healing) and functional (pain, hand function, quality of life) symptoms of RP secondary to SSc more than placebo.

Conditions

Raynaud Phenomenon Secondary to Systemic Sclerosis

Keywords

Raynaud Phenomenon; Systemic Sclerosis; Botulinum toxin A

Outcome Measures

Primary Outcomes (1)

• Absolute change from baseline in the number of RP attacks per week at 4 weeks

  Comparison between the 2 groups of the change (absolute) from baseline in the number of RP attacks per week at 4 weeks. An attack is defined as an episode of pallor or cyanosis (with or without pain, tingling or numbness). Subjects will keep a daily record of the number of RP attacks they experienced per day and the duration of each attack, from Day -14 to Day 0 (+/- 4 days) and from Day 14 to Day 28 ( +/- 4 days)

  4 weeks

Secondary Outcomes (9)

• Absolute change from baseline in the number of RP attacks per week at 12 and 24 weeks

  24 weeks

• Comparison between the 2 groups at 4, 12 and 24 weeks of follow-up after the treatment of the percentage of digital ulcers with complete healing

  24 weeks

• Comparison between the 2 groups at 4, 12 and 24 weeks of follow-up after the treatment of the number of new digital ulcers.

  24 weeks

• Comparison between the 2 groups at 4, 12 and 24 weeks of follow-up after the treatment of the change in Raynaud's pain score.

  24 weeks

• Comparison between the 2 groups at 4, 12 and 24 weeks of follow-up after the treatment of the change in Raynaud's Condition Score.

  24 weeks

Study Arms (2)

" BTX-A" group

EXPERIMENTAL

* BOTOX® solution * Saline serum * lidocaine/prilocaine cream * Nitrous oxide/oxygen (50%/50%) Intervention Description : * BOTOX 100 UNITES (Allergan, Courbevoie, France, and São Paulo, Brazil) Single injection schedule of BOTOX® in both hands, diluted in 2 ml of sterile serum saline, with a dosage of 50 UI (1 ml) by hand. Injections will be performed at the level of the distal palmar crease, targeting the neurovascular bundles in the 4 web spaces (0.25 ml/injection site) * between 2 to 3 hours before the procedure, application of lidocaine/prilocaine cream under an occlusive dressing (polyurethane film) in each palmar crease of the patients (1/2 tube/hand), according to the recommendations of the manufacturer * inhaled nitrous oxide/oxygen (50% / 50%) may be used, if needed

Drug: BOTOX® solution

Placebo group

PLACEBO COMPARATOR

* Saline serum * lidocaine/prilocaine cream * Nitrous oxide/oxygen (50%/50%) Intervention Description : * Sterile saline solution Single injection schedule of 2 ml (1 ml by hand) of serum saline, in both hands. Injections will be performed at the level of the distal palmar crease, targeting the neurovascular bundles in the 4 web spaces (0.25 ml/injection site). * between 2 to 3 hours before the procedure, application of lidocaine/prilocaine cream under an occlusive dressing (polyurethane film) in each palmar crease of the patients (1/2 tube/hand), according to the recommendations of the manufacturer of the lidocaine cream. * inhaled nitrous oxide/oxygen (50% / 50%) may be used, if needed

Drug: Placebo group

Interventions

BOTOX® solution DRUG

Botox solution + Saline serum + lidocaine/prilocaine cream + Nitrous oxide/oxygen (50%/50%)

" BTX-A" group

Placebo group DRUG

Placebo + lidocaine/prilocaine cream + Nitrous oxide/oxygen (50%/50%)

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years and older
• Diagnosed with systemic sclerosis (EULAR/ACR 2013 criteria ; or Leroy and Metsger criteria).
• Symptoms of Raynaud's phenomenon affecting both hands (not necessarily to equal extents)
• Frequency of Raynaud's attacks ≥ 5/week during cold weather
• Stable dose of phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, or calcium channel blockers defined as 1-month with no change in dose
• Ability to return/be available for follow-up evaluations
• Ability to fill the diary
• Ability/willingness to give informed consent
• Affiliation to any French social security regime

You may not qualify if:

• History of myasthenia gravis or Eaton Lambert syndrome
• Inflammatory myositis \<2 years or pre-existing motor neurone disease or upper limb motor neuropathy
• Reported allergy or hypersensitivity to any Botulinum toxin preparation or to lidocaine or other local anesthetic agent or to albumin or to inhaled nitrous oxide/oxygen.
• Active infection in either hand.
• women of child bearing potential without medically accepted method of birth control
• Patients who have previously undergone any vascular surgery on the upper extremity, including surgical sympathectomy or ever received botulinum toxin or planned to receive botulinum toxin in the next 6 months
• Cognitive impairment
• Iloprost scheduled the month following injections

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Tenon

Paris, 75020, France

Location

Related Publications (1)

• Senet P, Maillard H, Diot E, Lazareth I, Blaise S, Arnault JP, Pistorius MA, Boulon C, Cogrel O, Warzocha U, Riviere S, Malloizel-Delaunay J, Servettaz A, Sassolas B, Viguier M, Monfort JB, Janique S, Vicaut E; BRASS collaborators. Efficacy and Safety of Botulinum Toxin in Adults with Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2023 Mar;75(3):459-467. doi: 10.1002/art.42342. Epub 2022 Dec 14.

  PMID: 36066501 DERIVED

MeSH Terms

Conditions

Raynaud Disease; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Connective Tissue Diseases

Study Officials

• Patricia Senet, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: this study is double blind masking: Both participants and investigators are unaware of the intervention assignment, others including statistician
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, double-blind, randomized, placebo-controlled, parallel groups, phase III

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 24, 2018
• Study Start: October 15, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

FR (1)