Subcutaneous Injection of Sodium Thiosulfate for Ectopic Calcifications or Ossifications. A Pilot Study (ITS-PILOT)

December 4, 2023 updated by: University Hospital, Limoges

Ectopic soft tissue calcifications or ossifications can complicate the course of numerous diseases; most of them are rare or very rare. Even if the clinical, radiological and pathological presentation of ectopic calcifications and ossifications are different, the same hypotheses are discussed considering their hypothetical pathophysiology. Indeed, high calcium phosphate product, local cellular lesions and abnormal transdifferentiation of mesenchymal cells are regularly evoked when pathophysiology of such calcifications or ossifications are discussed. Apart from several case reports that have not been confirmed so far, no medical treatments are available, leading to significant pain and impairment of quality of life for patients. Therefore, only surgical treatment can be proposed when the volume or the consequences of these calcifications/ossifications become too important.

Sodium thiosulfate (STS) is currently used as a cyanide poisoning antagonist and a chemoprotectant against adverse effects of several chemotherapies such as Cisplatin. Numerous case reports and several studies have revealed the potential interest of STS in the treatment of uremic induced vascular or soft tissues calcifications. Recently, our group has developed an expertise in the use of STS for the treatment of ectopic soft tissue calcifications or ossifications. Considering these promising preliminary data, and their limits, we developed a strategy to treat soft tissue calcifications or ossifications based on a local administration of STS. The first results of this therapeutic strategy are highly promising and the local or systemic safety is satisfactory so far. These preliminary data also reported by others deserve to be confirmed in a prospective study.

We propose in this project to conduct a prospective open controlled phase II trial in order to assess the efficacy and the safety of intralesional administration of STS for the treatment of calcifications secondary to dermatomyositis or systemic sclerosis and ectopic ossifications secondary to pseudo-hypoparathyroidism 1a type (PHP1A/iPPSD2) (inactivating parathyroid hormone / parathyroid-hormone-related peptid (PTH/PTHrP) signalling disorder).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33000
      • Bron, France, 69500
        • Not yet recruiting
        • Hospice Civil de Lyon
        • Principal Investigator:
          • Justine BACCHETTA, MD
        • Contact:
      • Le Kremlin-Bicêtre, France, 94270
        • Recruiting
        • APHP - Hôpital Bicêtre
        • Contact:
        • Principal Investigator:
          • Agnès LINGLART, MD
      • Limoges, France, 87042
        • Recruiting
        • Chu de Limoges
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vincent GUIGONIS, MD
        • Sub-Investigator:
          • Anne-Laure FAUCHAIS, MD
        • Sub-Investigator:
          • Pascalle VERGNE-SALLE, MD
        • Sub-Investigator:
          • Didier MORIAU, MD
      • Paris, France, 75000
        • Recruiting
        • APHP - Hôpital Lariboisière
        • Contact:
        • Principal Investigator:
          • Korng EA, MD
      • Rouen, France, 76031
        • Not yet recruiting
        • Chu de Rouen
        • Contact:
        • Principal Investigator:
          • Mireille CASTANET, MD
      • Toulouse, France, 31000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient presenting with:

    • ectopic ossification secondary to iPPSD2 or
    • ectopic calcification secondary to dermatomyositis or
    • ectopic calcification secondary to systemic sclerosis
  • Patient aged 2 years or over
  • Indication of STS infusion validated by a multidisciplinary committee, based on the significant morbidity and/or functional impact of the targeted calcification/ossification
  • Patient with no planned surgery of the calcifications/ossifications for the twelve coming months
  • Women of childbearing potential on highly effective contraception (such as hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence)
  • Men with women of childbearing potential partners should use condoms during the whole treatment period and until 91 days after the last injection.
  • Informed consent signed by the patient / parents
  • Patient affiliated to the social security system

Exclusion Criteria:

  • Allergy to STS or one of the excipients used
  • Contraindication to local injection of STS
  • Anticoagulant therapy
  • Pregnant, parturient or breastfeeding woman
  • Patient deprived of freedom by a court judgment or an administrative decision
  • Patient undergoing psychiatric care under coercion
  • Legally protected adult patients (guardianship / curatorship)
  • Patient unable to give consent
  • Patient placed under judicial protection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treated
M0-M6: run-in phase (control) M6-M12: STS treatment phase
Drug: STS

M0-M6 (run-in phase): medical care and follow-up as usual

M6-M12 (STS phase):

  • Patients with iPPSD2 will be treated with subcutaneous infusion using a portable pump.
  • Patients with dermatomyositis or systemic sclerosis will be treated with repeated injections every two weeks.

Patients will receive a maximal total number of 11 STS injections. M12: final visit (V5): clinical evaluation, photograph and CT scan of the treated lesion, pain and quality of life evaluation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of the percentage of volume of the treated calcifications / ossifications
Time Frame: between Month 6 and Month 12
Calculation of percentage of volume evolution of the treated calcification / ossification between the beginning and the end of STS treatment, in each of the three diseases (dermatomyositis, systemic sclerosis and iPPSD2), evaluated on CT-scan measurements.
between Month 6 and Month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of the volume of the treated calcifications / ossifications
Time Frame: Month 0, Month 6 and Month 12
Calculation of volume of the treated calcification / ossification at (i) inclusion, the end of the run-in period (6 month) and after 6 months of local injections of STS in each disease (12 month), evaluated on CT-scan measurements.
Month 0, Month 6 and Month 12
Adverse events
Time Frame: Month 12
Collection of adverse events (clinical and biological): causality, severity, and seriousness during the STS treatment.
Month 12
Change of the Hounsfield density of the treated ectopic calcifications/ossifications
Time Frame: Month 0, Month 6 and Month 12
Hounsfield density analysis of the treated ectopic calcifications/ossifications at inclusion, the end of the run-in period (6 month) and after 6 months of local injections of STS (12 month), evaluated on CT-scan measurements.
Month 0, Month 6 and Month 12
Change of the percentage of patient with a clinically pertinent variation in pain
Time Frame: Between Month0 and Month 6 and Between Month 6 and Month 12
Calculation of Percentage of patients with a clinically pertinent variation in pain evaluated with pain scales: difference in hetero-evaluation scale of pain in children (HEDEN) ≥ 2 (2-7 years old) between M0-M6 and M6-M12
Between Month0 and Month 6 and Between Month 6 and Month 12
Change of the percentage of patient with a clinically pertinent variation in pain
Time Frame: Between Month0 and Month 6 and Between Month 6 and Month 12
Calculation of Percentage of patients with a clinically pertinent variation in pain evaluated with pain scales: difference in visual analogue pain intensity scale (VAS) score ≥ 2 (> 7 years old) between M0-M6 and M6-M12
Between Month0 and Month 6 and Between Month 6 and Month 12
Change of the percentage of patients with a clinically pertinent variation in quality of life
Time Frame: Between Month0 and Month 6 and Between Month 6 and Month 12
Calculation of percentage of patients with a clinically pertinent variation in quality of life : difference in PedsQL ≥ 5 (2-18 years old, using appropriates reports) between M0-M6 and M6-M12
Between Month0 and Month 6 and Between Month 6 and Month 12
Change of the percentage of patients with a clinically pertinent variation in quality of life
Time Frame: Between Month0 and Month 6 and Between Month 6 and Month 12
Calculation of percentage of patients with a clinically pertinent variation in quality of life : difference in Short Form 36 (SF36) score ≥ 20 (> 18 years old) between M0-M6 and M6-M12
Between Month0 and Month 6 and Between Month 6 and Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Limoges

Investigators

  • Principal Investigator: Vincent GUIGONIS, MD, University Hospital, Limoges

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2020

Primary Completion (Estimated)

June 6, 2025

Study Completion (Estimated)

June 6, 2025

Study Registration Dates

First Submitted

June 13, 2018

First Submitted That Met QC Criteria

June 27, 2018

First Posted (Actual)

July 11, 2018

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

December 4, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I17004 (ITS-PILOT)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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