The Effects of Botulinum Toxin on Oral Aperture in Patients With Scleroderma

This study will evaluate the use of botulinum toxin for microstomia (also known as reduced oral aperture) in scleroderma patients. Botox is a neurotoxin that functions as a paralytic by preventing the release of acetylcholine to inhibit muscle contracture and decrease fibrosis by decreasing differentiation of fibroblasts to myofibroblasts, decreasing expression of collagen, and increasing expression of matrix metalloproteinase1-3. The study will include three arms: the temporomandibular joint (TMJ) group who will receive injections of Botox to the masseter, the perioral group who will receive injections of Botox around the lips, and a control group who will receive no treatment for ROA. Outcome measurements will include measurement of oral aperture size through measurement inter-labial distance and between the upper and lower lips and the inter-incisal distance, patient satisfaction via a Skindex16 survey, mouth disability via the Mouth Handicap in Systemic Sclerosis Scale (MHISS), and patient and physician satisfaction using the Visual Analogic Scale (VAS). The maximum number of subjects to be consented for this study is 30. The study is expected to last four months per subject from time of consent to last clinical evaluation. Conditions that may result in a subject exiting the study prior to completion date include non-compliance, withdrawal of consent, or safety concerns such as adverse events as a result of treatment.

Study Overview

• Status: Completed
• Conditions: Scleroderma
• Intervention / Treatment: Biological: Botulinum toxin(Botox)

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-8802
      • UT Southwestern Medical Center at Dallas - Dermatology Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ddiagnosis of scleroderma (defined by the 2013 Classification Criteria for Systemic Sclerosis4,5)23,24 ) who also have microstomia (reduced oral aperture), defined as an inter-incisal distance less than 50 mm 6-7)m13,14 .
2. Male and female subjects.
3. English and non-English speakers.
4. Subjects aged 18 years old to 65 years old will be considered

Exclusion Criteria

1. Patients under 18 years old will be excluded.
2. Patients with a known history of a hypersensitivity to any Botox formulation or to any of the components in the formulation,
3. Active skin infection at the proposed injection site.
4. Concomitant neuromuscular disorder.
5. Pregnant or lactating.
6. Missing incisors.
7. treatment with: cyclophosphamide, Ultraviolet A-1 therapy, or topical calcitriol..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: the temporomandibular joint (TMJ) group; This study will evaluate the use of botulinum toxin for microstomia (reduced oral aperture) in scleroderma patients. The TMJ group will be injected with two units of Botox into four different injection points to each masseter (16 units of Botox total) at the initial visit. No additional Botox will be injected in subsequent visits. Botox is a neurotoxin that functions as a paralytic by preventing the release of acetylcholine to inhibit muscle contracture and decrease fibrosis by decreasing differentiation of fibroblasts to myofibroblasts, decreasing expression of collagen, and increasing expression of matrix metalloproteinase1	Biological: Botulinum toxin(Botox); This study will evaluate the use of botulinum toxin for reduced oral aperture in scleroderma patients. Botox is a neurotoxin that functions as a paralytic by preventing the release of acetylcholine to inhibit muscle contracture and decrease fibrosis by decreasing differentiation of fibroblasts to myofibroblasts, decreasing expression of collagen, and increasing expression of matrix metalloproteinase.
Experimental: the perioral group; Biological/Vaccine: Botulinum toxin(Botox) This study will evaluate the use of botulinum toxin for microstomia (reduced oral aperture) in scleroderma patients. The perioral group will be injected with two units of Botox into eight different injection points (16 units of Botox total) around the lips (in the orbicularis oris). Botox is a neurotoxin that functions as a paralytic by preventing the release of acetylcholine to inhibit muscle contracture and decrease fibrosis by decreasing differentiation of fibroblasts to myofibroblasts, decreasing expression of collagen, and increasing expression of matrix metalloproteinase1-3.	Biological: Botulinum toxin(Botox); This study will evaluate the use of botulinum toxin for reduced oral aperture in scleroderma patients. Botox is a neurotoxin that functions as a paralytic by preventing the release of acetylcholine to inhibit muscle contracture and decrease fibrosis by decreasing differentiation of fibroblasts to myofibroblasts, decreasing expression of collagen, and increasing expression of matrix metalloproteinase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in inter-labial distance	Inter-labial distance is defined as the distance between the upper and lower lip at maximum mouth opening. Distance will be measured using digital calipers by the same operator	This will be measured at baseline before treatment, 2 weeks after treatment, and 3 months after treatment.
Changes interincisal distance	Interincisal distance is defined by the didistance between upper and lower incisor at maximum mouth opening. Distance will be measured using digital calipers by the same operator	This will be measured at baseline before treatment, 2 weeks after treatment, and 3 months after treatment.
quality of life via a Skindex16 survey	This is a patient quality of life survey using the skindex 16 survey form.	This information will be collected at baseline before treatment, 2 weeks after treatment, and 3 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the inter-commissural distance	Inter-commissural distance is defined by the distance from corner to corner at the angle of the lip (also known as the oral commissures). Distance will be measured using digital calipers by the same operator.	This will be measured at baseline before treatment, 2 weeks after treatment, and 3 months after treatment.]
Changes in the Mouth Handicap in Systemic Sclerosis Scale (MHISS)	Mouth disability will be assessed via the Mouth Handicap in Systemic Sclerosis Scale (MHISS). MHISS range from 0 to 48 with 48 being worse disability	This will be measured at baseline before treatment, 2 weeks after treatment, and 3 months after treatment.]

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Heather Goff, MD, UT southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2020
• Primary Completion (Actual): April 22, 2021
• Study Completion (Actual): April 22, 2021

Study Registration Dates

• First Submitted: July 19, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: STU-2020-0169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: To be decided by research team

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes