Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis
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|ClinicalTrials.gov Identifier: NCT03267277|
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : June 13, 2018
Dermatomyositis (DM) and juvenile dermatomyositis (JDM) cause inflammation in the muscles. People with DM and JDM can develop calcium deposits in places they should not, known as calcinosis. Calcinosis can be painful and cause disabilities and other problems. Researchers want to learn more about calcinosis to find treatments for it.
To test if sodium thiosulfate (STS) can treat people with DM with calcinosis.
People ages 7 and older who have moderate or severe calcinosis. They must have stable DM and calcium deposits in the torso or at least 2 limbs.
Participants will be screened with:
- Medical history
- Physical exam
- Muscle strength and function tests
- Blood and urine tests
Participants will have several visits:
- 7-day pre-treatment visit about 10 weeks before starting STS
- Treatment visits over 10 weeks. They will get STS 3 times a week through IV infusion. They may be hospitalized the whole time. If they tolerate the drug, they may be discharged at certain times. During these times, they will return for the infusions.
- 3- to 5-day post-treatment visits 24 weeks and 62 weeks after starting STS.
Visits may include repeats of screening tests and:
- Scans: They lie in a machine that takes pictures of the body. They may be injected with a radioactive agent.
- Durometry: A small instrument applies pressure on the skin or exposed calcinosis.
- Measurements of blood flow in the arms and fingernail blood vessels
- Photographs of the skin
- Kidney ultrasound
- Tests of kidney function
- Calcinosis aspiration: A needle placed into areas of calcinosis removes liquid.
|Condition or disease||Intervention/treatment||Phase|
|Dermatomyositis Idiopathic Inflammatory Myopathies||Drug: Sodium Thiosulfate||Phase 2|
Expanded Access : National Institute of Environmental Health Sciences (NIEHS) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
Calcinosis, a serious complication of dermatomyositis, involves deposition of calcium (carbonate apatite) in soft tissue, and can result in negative impacts on quality of life and physical function. To date, there are no known effective therapies that are approved for the treatment of dermatomyositis-associated calcinosis, and there is no consensus within the medical community on the optimum treatment strategy for this often-debilitating condition.
A few reports in the literature describe treatment successes with a variety of therapeutics; however, these data are from anecdotal reports or case series and thus provide limited scientific evidence of effectiveness. Recently published reports as well as personal observations within our group have suggested that intravenous sodium thiosulfate treatment may benefit calcinosis patients. In order to gather more robust data on the utility of this medication in the treatment of calcinosis associated with adult and juvenile dermatomyositis, we propose to evaluate its effects in the context of a prospective clinical trial.
We plan to enroll participants at a single center into a single-arm, open-label study, with the overall objective of evaluating the efficacy and safety of intravenous sodium thiosulfate use in patients with moderate to severe extensive calcinosis associated with juvenile and adult dermatomyositis.
The study will enroll a maximum of 18 participants over 4 years into the full study, but up to 250 patients may screen for study entry. Eligible patients will be age 7 or older, and will have extensive calcinosis (defined as calcinosis involving the torso or 2 extremities) and moderate to severe calcinosis (indicated by a calcinosis activity visual analogue scale score of greater than or equal to 3.5 cm out of 10 cm).
Two separate evaluations performed at the NIH prior to initiation of therapy will be used as baseline data to compare in a pairwise manner to the change in assessments following treatment with sodium thiosulfate, with all other medications remaining stable. Study treatment will be 16 g/m2 sodium thiosulfate administered 3 times weekly over a period of 10 weeks at the NIH. Subjects who complete 10 weeks of treatment or reach the primary end point by week 6 will be considered completers. Following the treatment period, all participants will return to the NIH for evaluations at weeks 24 and 62.
The primary outcome will be change in calcinosis activity visual analogue scale score from week 0 to week 10 on therapy, compared to the baseline change in calcinosis activity visual analogue scale score from week -10 to week 0 pre-treatment. Secondary measures will evaluate safety and changes in components of the Calcinosis Assessment Tool, clinical assessments of calcinosis, Mawdsley Calcinosis Questionnaire, quality of life, functional disability, muscle testing (manual and quantitative), laboratory parameters (muscle enzymes, inflammatory markers, and endothelial activation markers), gene expression, calcification pathogenesis, time to improvement, and imaging. Myositis disease activity and damage will also be assessed by validated measures.
A number of research studies will be incorporated into this clinical trial in an attempt to understand the immunologic markers associated with calcification in dermatomyositis as well as the immunologic effects of sodium thiosulfate treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Study of Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis|
|Actual Study Start Date :||October 5, 2017|
|Estimated Primary Completion Date :||May 12, 2021|
|Estimated Study Completion Date :||June 18, 2025|
Patient will be assessed for 10 weeks off treatment and then will receive 10 weeks of treatment. They will return at weeks 24 and 52 for safety and sustainability of efficacy assessments.
Drug: Sodium Thiosulfate
Sodium thiosulfate is a calcium chelator
- Change in calcinosis severity visual analogue scale score from week 0 to week 10 on therapy, compared to the baseline change in calcinosis severity visual analogue scale score from week -10 to week 0 pre treatment. [ Time Frame: Week -10, 0, 10 ]
- Greater improvement in quality of life score (CHQ-PF50 for children, SF-36 for adults) from Week 0 to Week 10, compared with any change in quality of life score observed during the pre-treatment period (from Week -10 to Week 0). [ Time Frame: Week -10,0,10 ]
- Changes in components of quality of life over time, as measured by quality of life questionnaires (e.g., SF-36, CHQ-PF50, PROMIS, Skindex-29) [ Time Frame: Week -10,0,10 ]
- Changes in functional disability over time, measured by CHAQ/HAQ, CMAS/AMAT/Myositis Functional Index, and physical therapy-related assessments (e.g., range of motion, 6-minute walk, timed up and go, sit to stand, Motor Functional Measure (MFM)) [ Time Frame: Week -10,0,10 ]
- Change in muscle strength over time, measured by manual and quantitative muscle testing. [ Time Frame: Week -10,0,10 ]
- Improvement of calcinosis lesions, assessed by Calcinosis Assessment Tool, durometry measurements, photography, and imaging studies [ Time Frame: Week -10,0,10 ]
- Changes in gene expression, measured by RNA and protein analyses (e.g., to evaluate changes due to therapy, or differences between responders and non-responders to therapy) [ Time Frame: Week -10,0,10 ]
- Incidence and severity of adverse events, including laboratory abnormalities, over time [ Time Frame: Week -10 to week 52 ]
- Improvement in or stabilization of myositis activity and damage, as assessed by the IMACS core set measures [ Time Frame: Week -10,0,10 ]
- Validation of the Calcinosis Assessment Tool [ Time Frame: Week -10,0,10 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267277
|Contact: Adam I Schiffenbauer, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Adam I Schiffenbauer, M.D.||National Institute of Environmental Health Sciences (NIEHS)|