Safety and Efficacy of Topical Sodium Metabisulfite for the Treatment of Calcinosis in Patients With Systemic Sclerosis

NCT06155578 | Unknown Phase 1

• 1 other identifier: 220421002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective placebo-controlled trial will enroll 20 patients with SSc and at least one calcinotic lesion of the hands that is palpable on physical examination and measurable on hand radiographs. Each subject will undergo a screening evaluation 1 month before treatment with the study drug is initiated. Each subject will be instructed to blindly self-apply either topical 25% sodium metabisulfite or placebo cream twice daily. In-person follow-up evaluations will be performed after 4-months, with monthly telehealth follow-up visits to ensure adherence and arrange study drug refill deliveries.

Conditions

Systemic Sclerosis; Calcinosis

Keywords

Systemic Sclerosis; calcinosis; sodium metabisulfite; topical

Outcome Measures

Primary Outcomes (2)

• To assess the safety and tolerability of using topical 25% SM applied twice daily in SSc patients with calcinosis affecting the hands

  The primary assessment of safety will be the development of adverse events. Any significant changes to the subject's medical condition, physical examination, and concomitant medications will be documented throughout the course of the study. Any untoward medical experience will be recorded as an adverse event.

  4 months

• To assess the efficacy of topical 25% SM versus placebo in stabilizing the calcinosis burden or reducing the radiographic progression of calcinosis over four months.

  Radiograph of the hands will be scored using the SCTC radiographic calcinosis scroing system

  4 months

Secondary Outcomes (3)

• To assess the effect of topical 25% SM on the change in the Mawdsley Calcinosis Questionnaire, and patient and physician assessment of calcinosis severity over four months.

  4 months

• To assess the effect of topical 25% SM on the change in size of calcinosis on ultrasound.

  4 months

• To assess the presence of markers of vascular damage and inflammation by tape stripping in SSc patients with calcinosis.

  4 months

Study Arms (2)

Sodium metabisulfite cream

ACTIVE COMPARATOR

Sodium metabisulfite prepared in pediatric cold cream (water in oil emulsion) at a concentration of 25% to be applied on calcinosis topically twice daily.

Drug: Topical 25% sodium metabisulfite (SM) in pediatric cold cream

Placebo cream

PLACEBO COMPARATOR

Pediatric cold cream (water in oil emulsion) to be applied on calcinosis topically twice daily.

Drug: Placebo

Interventions

Topical 25% sodium metabisulfite (SM) in pediatric cold cream DRUG

Topical 25% sodium metabisulfite (SM) in pediatric cold cream will be applied twice daily on hand calcinosis.

Also known as: cold cream

Sodium metabisulfite cream

Placebo DRUG

Pediatric cold cream will be applied twice daily on hand calcinosis.

Also known as: cold cream

Placebo cream

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Age \> 18 years of age
• Diagnosis of limited or diffuse cutaneous systemic sclerosis (SSc) according to the revised 2013 ACR/EULAR classification criteria for SSc (21)
• Radiological and physical examination evidence of at least one subcutaneous calcium deposition in the hands that is clinically apparent as part of routine clinical care.
• If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits
• Oral corticosteroids (≤ 5 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to screening and throughout the study
• Oral CCB, alpha-1-antagonists, ACE-inhibitors, angiotensin receptor blockers, and protein-pump inhibitors are permitted if the doses are stable for 4 weeks prior to screening and throughout the study.

You may not qualify if:

• Rheumatic disease other than SSc
• Allergy to sodium metabisulfite
• Pregnant or nursing women
• Concurrent malignancy except non-melanoma skin cancers
• Patients receiving bisphosphonates, warfarin, colchicine, minocycline, intravenous immunoglobulins, or biological agents specifically abatacept or rituximab within 4 weeks of screening
• Patients receiving local treatments for calcinosis of the hands including surgical removal or intralesional steroid injections within 12 weeks of screening or throughout the study.
• Patients who have participated in another clinical trial of an investigative agent within 30 days of screening (or 5 half-lives of the investigational drug, whichever is longer)
• Patients with a history of drug or alcohol abuse within 6 months of screening
• Any medical condition that, in the opinion of the investigator, might interfere with the subject's participation in the study or poses an added risk for the subject
• Inability to comply with study and follow-up procedures

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• Liga Panamericana de Asociaciones de Reumatologia (PANLAR): collaborator

Study Sites (1)

Antonia Valenzuela

Santiago, 8330077, Chile

Location

Related Publications (19)

• Ricardo JW, Sun HY, Gorji M, Sebaratnam DF. Topical sodium thiosulfate as treatment of calcinosis cutis: Case series and systematic review. J Am Acad Dermatol. 2022 Aug;87(2):443-444. doi: 10.1016/j.jaad.2021.09.013. Epub 2021 Sep 16. No abstract available.

  PMID: 34537249 BACKGROUND

• Valenzuela A, Baron M; Canadian Scleroderma Research Group; Herrick AL, Proudman S, Stevens W; Australian Scleroderma Interest Group; Rodriguez-Reyna TS, Vacca A, Medsger TA Jr, Hinchcliff M, Hsu V, Wu JY, Fiorentino D, Chung L. Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study. Semin Arthritis Rheum. 2016 Dec;46(3):344-349. doi: 10.1016/j.semarthrit.2016.05.008. Epub 2016 Jun 2.

  PMID: 27371996 BACKGROUND

• Valenzuela A, Baron M, Rodriguez-Reyna TS, Proudman S, Khanna D, Young A, Hinchcliff M, Steen V, Gordon J, Hsu V, Castelino FV, Schoenfeld S, Li S, Wu JY, Fiorentino D, Chung L. Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis. Semin Arthritis Rheum. 2020 Oct;50(5):891-896. doi: 10.1016/j.semarthrit.2020.06.007. Epub 2020 Jun 17.

  PMID: 32898758 BACKGROUND

• Cruz-Dominguez MP, Garcia-Collinot G, Saavedra MA, Medina G, Carranza-Muleiro RA, Vera-Lastra OL, Jara LJ. Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis. Clin Rheumatol. 2017 Jan;36(1):111-117. doi: 10.1007/s10067-016-3412-9. Epub 2016 Oct 7.

  PMID: 27718018 BACKGROUND

• Bartoli F, Fiori G, Braschi F, Amanzi L, Bruni C, Blagojevic J, Bellando-Randone S, Cometi L, de Souza Mueller C, Guiducci S, Rasero L, Epifani F, Furst DE, Matucci-Cerinic M. Calcinosis in systemic sclerosis: subsets, distribution and complications. Rheumatology (Oxford). 2016 Sep;55(9):1610-4. doi: 10.1093/rheumatology/kew193. Epub 2016 May 30.

  PMID: 27241706 BACKGROUND

• Gauhar R, Wilkinson J, Harris J, Manning J, Herrick AL. Calcinosis preferentially affects the thumb compared to other fingers in patients with systemic sclerosis. Scand J Rheumatol. 2016 Jul;45(4):317-20. doi: 10.3109/03009742.2015.1127412. Epub 2016 Jan 26.

  PMID: 26812367 BACKGROUND

• Valenzuela A, Song P, Chung L. Calcinosis in scleroderma. Curr Opin Rheumatol. 2018 Nov;30(6):554-561. doi: 10.1097/BOR.0000000000000539.

  PMID: 30124603 BACKGROUND

• Gorrepati PL, Smith GP. Treatments for calcinosis cutis in autoimmune connective tissue diseases. J Am Acad Dermatol. 2022 Nov;87(5):1211-1212. doi: 10.1016/j.jaad.2022.03.029. Epub 2022 Mar 22. No abstract available.

  PMID: 35331808 BACKGROUND

• Nigwekar SU. Multidisciplinary approach to calcific uremic arteriolopathy. Curr Opin Nephrol Hypertens. 2015 Nov;24(6):531-7. doi: 10.1097/MNH.0000000000000175.

  PMID: 26371529 BACKGROUND

• Bair B, Fivenson D. A novel treatment for ulcerative calcinosis cutis. J Drugs Dermatol. 2011 Sep;10(9):1042-4.

  PMID: 22052275 BACKGROUND

• Goossens J, Courbebaisse M, Caudron E, Bahans C, Vacquerie V, Melchior J, Salle PV, Moesch C, Daudon M, Frocht V, Richette P, Ea HK, Guigonis V. Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases. Semin Arthritis Rheum. 2017 Dec;47(3):451-455. doi: 10.1016/j.semarthrit.2017.05.013. Epub 2017 Jun 17.

  PMID: 28779847 BACKGROUND

• Baumgartner-Nielsen J, Olesen AB. Treatment of Skin Calcifications with Intra-lesional Injection of Sodium Thiosulphate: A Case Series. Acta Derm Venereol. 2016 Feb;96(2):257-8. doi: 10.2340/00015555-2206. No abstract available.

  PMID: 26258586 BACKGROUND

• Song P, Fett NM, Lin J, Merola JF, Costner M, Vleugels RA. Lack of response to intravenous sodium thiosulfate in three cases of extensive connective tissue disease-associated calcinosis cutis. Br J Dermatol. 2018 Jun;178(6):1412-1415. doi: 10.1111/bjd.15783. Epub 2018 Mar 7.

  PMID: 28667747 BACKGROUND

• Mageau A, Guigonis V, Ratzimbasafy V, Bardin T, Richette P, Urena P, Ea HK. Intravenous sodium thiosulfate for treating tumoral calcinosis associated with systemic disorders: Report of four cases. Joint Bone Spine. 2017 May;84(3):341-344. doi: 10.1016/j.jbspin.2016.10.009. Epub 2016 Dec 7.

  PMID: 27955821 BACKGROUND

• Del Barrio-Diaz P, Moll-Manzur C, Alvarez-Veliz S, Vera-Kellet C. Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy. Br J Dermatol. 2016 Sep;175(3):608-11. doi: 10.1111/bjd.14412. Epub 2016 Apr 17.

  PMID: 26799451 BACKGROUND

• Patra S, Gupta V, Kumar R, Verma KK. Clinical and radiological improvement in idiopathic calcinosis cutis with topical 25% sodium metabisulfite. Int J Dermatol. 2017 Dec;56(12):1464-1465. doi: 10.1111/ijd.13789. Epub 2017 Oct 26. No abstract available.

  PMID: 29076152 BACKGROUND

• Chung L, Valenzuela A, Fiorentino D, Stevens K, Li S, Harris J, Hutchinson C, Assassi S, Beretta L, Lakshminarayanan S, Rodriguez-Reyna TS, Denton CP, Taillefer RG, Herrick AL, Baron M; Scleroderma Clinical Trials Consortium Calcinosis Working Group. Validation of a novel radiographic scoring system for calcinosis affecting the hands of patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2015 Mar;67(3):425-30. doi: 10.1002/acr.22434.

  PMID: 25155948 BACKGROUND

• Valenzuela A, Stevens K, Chung MP, Rodriguez-Reyna TS, Proudman S, Baron M, Castelino FV, Hsu V, Green L, Galdo FD, Li S, Fiorentino D, Chung L. Change in calcinosis over 1 year using the scleroderma clinical trials consortium radiologic scoring system for calcinosis of the hands in patients with systemic sclerosis. Semin Arthritis Rheum. 2022 Apr;53:151980. doi: 10.1016/j.semarthrit.2022.151980. Epub 2022 Feb 10.

  PMID: 35183935 BACKGROUND

• Gamissans M, Giavedoni P, Roe E, Sanchez J, Quintana-Codina M, Garbayo-Salmons P, Vidal D, Riera-Marti N, Lopez-Llunell C, Romani J, Wortsman X. Multicentric Study on High-Frequency Ultrasound Characterization of Calcium Deposits in Dermal and Subcutaneous Calciphylaxis and Calcinosis. J Ultrasound Med. 2022 Aug;41(8):1975-1979. doi: 10.1002/jum.15878. Epub 2021 Nov 10.

  PMID: 34755910 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Calcinosis

Interventions

sodium metabisulfite

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Antonia Valenzuela, MD, MS

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonia Valenzuela, MD, MS

CONTACT

+56223549019; antonia.valenzuela@uc.cl

Carolina Iturriaga, RN

CONTACT

carolina.iturriaga@uc.cl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The research products will be prepared in pediatric cold cream (water in oil emulsion) at a concentration of 25% or placebo, with identical packing and labeling, each identified by an exclusive number ID which will be assigned by a researcher not involved with the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MS, Assistant Professor at Pontificia Universidad Católica de Chile

Model Details: Randomized placebo-controlled trial with subjects allocated to topical 25% sodium metabisulfite or placebo cream twice daily.

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 4, 2023
• Study Start: January 2, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: End of study
• Access Criteria: Upon reasonable request

Locations

CL (1)