Topical Sodium Thiosulfate and Fractional Carbon Dioxide Laser in Treating Dermatomyositis Associated Calcinosis

• ClinicalTrials.gov Identifier: NCT01572844
• Recruitment Status: Completed
• First Posted: April 6, 2012
• Results First Posted: November 29, 2017
• Last Update Posted: November 29, 2017
• Sponsor: Alison Ehrlich
• Information provided by (Responsible Party): Alison Ehrlich, George Washington University

Study Description

Brief Summary:

Dermatomyositis is an inflammatory muscle disorder that is often associated with many skin findings. One of the skin findings seen in up to 50% of individuals with juvenile dermatomyositis, an early onset form of this condition, and up to 20-30% of adult dermatomyositis patients who have not responded to treatment, is calcinosis, or deposits of calcium within the skin and muscle tissue. In addition to being cosmetically unappealing, involvement of deeper tissues with calcinosis may lead to contractures, or shortening of muscles, which may have a significant impact on functioning and quality of life. Unfortunately, there is no known effective treatment of dermatomyositis associated calcinosis. However, recent reports have shown that a medication called sodium thiosulfate has been effective in treating individuals with calciphylaxis, a condition where calcium is deposited within blood vessels, and with tumoral calcinosis, a genetic form of calcification, when receiving this medication by vein. In addition, recent advances in laser technology have led to the development of methods that may allow topical medications to penetrate deeper layers of the skin. The investigators have designed a pilot study to evaluate the use of topical sodium thiosulfate solution in treating superficial calcinosis in individuals with juvenile and adult dermatomyositis. The investigators will use laser to assist in the delivery of this medication to areas of calcinosis.

Condition or disease	Intervention/treatment	Phase
Calcinosis	Device: Fractionated Carbon Dioxide (FCO2) Laser; Drug: Sodium thiosulfate	Phase 2

Detailed Description:

Five individuals who meet the eligibility criteria will take part in this study. They will have a variety of assessments performed throughout the treatment period in order to evaluate both dermatomyositis and calcinosis severity and their potential response to fractional carbon dioxide and sodium thiosulfate treatment. A medical history will be taken and baseline assessments will be performed during the screening period. Serum creatinine kinase levels will be determined on this visit and repeated at the end of the study (week 20); these levels will be one measure of monitoring disease activity during the study. One calcinosis lesion will be treated, assessed, and followed. If a second calcinosis lesion is present, it will act as a control (not treated). Two weeks prior to the first treatment session, an optional (not required) skin biopsy of the target (treated) calcinosis lesion will be offered to the the first 3 patients ≥ 18 years of age to determine optimal fractional carbon dioxide laser settings that will be used for treatment. Area and durometer (a device that measures hardness) measurements and photographs of the calcinosis lesions will be performed at weeks 0,4,8,12,16,and 20. One x-ray of the control and one x-ray of the target calcinosis lesion will also be performed during the screening period and at week 20. Assessment of muscle strength, physical functioning, endurance, and range of motion, as well as myositis activity outside of the muscles will be performed during the screening period and at weeks 8 and 20. Myositis damage assessment will be performed at the screening period and at week 20. Questionnaires to assess physical functioning pertaining to activities of daily living and quality of life, as well as the quality of life related to skin disease and the calcinosis lesions will be completed during the screening period and at weeks 8 and 20. Treatment of the target calcinosis lesion with fractional carbon dioxide laser and topical sodium thiosulfate will occur on weeks 0,2,4,6,8,10,12,14,16,and 18. Each patient will receive a total of 8-10 treatments over a 6 month period. Assessments for any side effects from the treatment will be performed prior to each treatment session on weeks 0,2,4,6,8,10,12,14,16,18, and 20.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• Official Title: Novel Drug Delivery of Sodium Thiosulfate for Calcinosis Associated With Adult and Juvenile Dermatomyositis
• Study Start Date: August 2012
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment lesion; Lesion A, target lesion, 2cm x 2cm (+/- 1cm) treated with 1 pass Fractionated Carbon Dioxide (FCO2) Laser followed by application of 4 ml of 5% topical sodium thiosulfate solution (STS), 8 to 10 treatments over 6 months.	Device: Fractionated Carbon Dioxide (FCO2) Laser; At each treatment visit, a 2 X 2 cm (+/- 1 cm) area of the target calcinosis lesions will be treated with one pass of the Candela QuadraLase (TM) FCO2 laser. Patients will receive a total of 8-10 treatments over a 6 month period.; Other Name: Candela QuadraLase (TM); Drug: Sodium thiosulfate; Following treatment with FCO2 laser, 4 ml of 5% Sodium Thiosulfate solution will be applied to the treatment site only. Subjects will receive a total of 8-10 treatments over a 6 month period.
No Intervention: No Treatment Lesion; Lesion B, similar area of calcinosis on the same patient, which did not receive treatment is evaluated.

Outcome Measures

Primary Outcome Measures :

1. Change in Dermatomyositis-associated Calcinosis of a Single Lesion by Assessing Its Severity as Measured by a Difference in Physician Calcinosis Visual Analog Scales. [ Time Frame: Change from Visit 2 to Visit 12 (week 20) ]
   Change in dermatomyositis-associated calcinosis of a single lesion by assessing its severity as measured by a difference in Physician Calcinosis Visual Analog Scales. The Visual Analog Scale range is from zero (0) to ten (10). Zero (0) being no evidence of disease activity and ten (10) being extremely active or severe disease activity. A negative percent change indicates improvement in the lesion.

Secondary Outcome Measures :

1. Change in Dermatomyositis-associated Calcinosis of a Single Lesion by Assessing Its Hardness as Measured by a Difference in Durometer (Rex Durometer Model 1600, Type OO) Measurements. [ Time Frame: Change from Baseline (Visit 1) at Final Assessment (Visit 12, week 20). ]
   Change in dermatomyositis-associated calcinosis of a single lesion by assessing its hardness as measured by a difference in durometer (Rex durometer Model 1600, Type OO) measurements. The range of a durometer is from 0 to 100. The higher the durometer reading, the harder the lesion. Improvement in the lesion hardness would result in a negative change over time.
2. Change in Dermatomyositis-associated Calcinosis of a Single Lesion by Assessing Its Severity as Measured by a Difference in Patient Calcinosis Visual Analog Scales. [ Time Frame: Change from Visit 2 to Visit 12 (week 20) ]
   Change in dermatomyositis-associated calcinosis of a single lesion by assessing its severity as measured by a difference in Patient Calcinosis Visual Analog Scales. The scale ranges from zero (0) to ten (10). Zero (0) being no evidence of disease activity and ten (10) being extremely active or severe disease activity. A negative change would indicate improvement in the disease activity. A positive change would indicate worsening of disease activity.
3. Change in Size of Dermatomyositis-associated Calcinosis Area on Lesions as Measured by a Difference in Plain Film (X-ray) Studies. [ Time Frame: Change from Visit 2 to Visit 12 (week 20) ]
   Change in dermatomyositis-associated calcinosis as measured by a difference in centimeters in plain film (x-ray) studies. X rays were compared between baseline and final assessment for any changes.
4. Change in Patient Functionality and/or Quality of Life. [ Time Frame: Change from Visit 1 to Visit 12 (week 20) ]
   This will be assessed through the use of the Dermatology Life Quality Index (DLQI), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (CHAQ), Manual Muscle Testing (MMT8), and range of motion evaluations. DLQI index scores range from 0 to 30. The higher the score, the more quality of life is impaired.Change in scores from baseline to final assessment yielding a negative percent change indicate an improvement in DLQI. HAQ scales range from 0 to 3. The higher the score, the greater the disability. Change in scores from baseline to final assessment yielding a negative percent change indicate an improvement in the HAQ. MMT8 testing results in a score between 0 and 150. The higher the score, the more normal the function of the muscle. A positive percent change would indicate an improvement in MMT8 testing results.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Individuals of both sexes and of all ethnicities who wish to participate in the study and who have signed a written informed consent form to participate.
• Subjects must be between the ages of 18-65 years.
• Subjects must have a diagnosis of adult or juvenile dermatomyositis.
• All patient must be on stable therapy for their condition. Overall disease activity must be considered mild or in remission.
• Patients must have a history of failing at least one therapy for calcinosis associated with dermatomyositis.
• Patients must have at least one localized area of superficial calcinosis with easily identifiable landmarks. Whenever possible, subjects will have a second localized area of superficial calcinosis that can serve as a control lesion for repeated assessment.
• The calcinosis lesion being treated and the control calcinosis lesion must be stable (not increasing in size) based on the patient's history.
• Patients must be able to attend all treatment sessions and assessment visits at our Washington, District of Columbia clinic over the 20 week period.

Exclusion Criteria:

• Unstable dermatomyositis, or moderate or severely active juvenile dermatomyositis.
• Serum creatine kinase greater than or equal to three times the upper limit of normal.
• Inability to make study visits or anticipated poor compliance.
• Active infections, including a history of recurrent superinfection or cellulitis at the sites of calcinosis (> 1 prior episode).
• Pregnant females or nursing mothers.
• Life threatening illness that would interfere with the patient's ability to complete the study.
• Known or suspected history of drug or alcohol abuse within the past 6 months.
• Participation in another clinical experimental therapeutic study within 30 days of screening visit.
• History of severe illness or any other condition that would make the patient unsuitable for the study.
• History of hepatitis B, hepatitis C, HIV, cancer-associated myositis, or an underlying malignancy.

Contacts and Locations

Locations

United States, District of Columbia

The George Washington University Medical Faculty Associates Departments of Dermatology and Rheumatology

Washington, District of Columbia, United States, 20037

Sponsors and Collaborators

Alison Ehrlich

Investigators

• Principal Investigator: Alison Ehrlich, MD; George Washington University
• Principal Investigator: Gary Simon, MD; George Washington University
• Study Chair: James Katz, MD; George Washington University
• Study Chair: Gulnara Mamayrova, MD; George Washington University
• Study Chair: Laura Roosa; George Washington University
• Study Chair: Andrea Morris, MD; George Washington University

More Information

• Responsible Party: Alison Ehrlich, Principal Investigator, George Washington University
• ClinicalTrials.gov Identifier: NCT01572844
• Other Study ID Numbers: 121131
• First Posted: April 6, 2012
• Results First Posted: November 29, 2017
• Last Update Posted: November 29, 2017
• Last Verified: November 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Alison Ehrlich, George Washington University:

Dermatomyositis; Superficial calcinosis; Fractional carbon dioxide laser; Sodium thiosulfate

Additional relevant MeSH terms:

Dermatomyositis; Calcinosis; Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Sodium thiosulfate; Antidotes; Protective Agents; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Chelating Agents; Sequestering Agents