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

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ClinicalTrials.gov Identifier: NCT03582800
Recruitment Status : Not yet recruiting
First Posted : July 11, 2018
Last Update Posted : July 11, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Systemic Sclerosis Dermatomyositis iPPSD2 Drug: STS Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intralesional Sodium Thiosulfate for Ectopic Calcifications or Ossifications. A Pilot Study
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022


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.





Primary Outcome Measures :
  1. 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 calcifications / ossifications 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.


Secondary Outcome Measures :
  1. Change of the volume of the treated calcifications / ossifications [ Time Frame: Month 0, Month 6 and Month 12 ]
    Calculation of volume of the treated calcifications / ossifications 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.

  2. Adverse events [ Time Frame: Month 12 ]
    Collection of adverse events (clinical and biological): causality, severity, and seriousness during the STS treatment.

  3. 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.

  4. 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 Newborn Pain and Discomfort Scale (EDIN) ≥ 3 (6 months- 2 years old) between M0-M6 and M6-M12

  5. 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

  6. 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

  7. 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 quality of life of the newborn (QualIN) score ≥ 10% (6 months - 2 years old) between M0-M6 and M6-M12

  8. 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

  9. 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



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Ages Eligible for Study:   6 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 6 months 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582800


Contacts
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Contact: Vincent GUIGONIS, MD 555056358 ext +33 vincent.guigonis@unilim.fr
Contact: Claire BAHANS claire.bahans@chu-limoges.fr

Locations
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France
CHU de BORDEAUX Not yet recruiting
Bordeaux, France, 33000
Contact: Marie-Elise TRUCHETET, MD       marie-elise.truchetet@chu-bordeaux.fr   
Principal Investigator: Marie-Elise TRUCHETET, MD         
ApHp - Hôpital Bicêtre Not yet recruiting
Le Kremlin-Bicêtre, France, 94270
Contact: Agnès LINGLART, MD       agnes.linglart@aphp.fr   
Principal Investigator: Agnès LINGLART, MD         
CHU de Limoges Not yet recruiting
Limoges, France, 87042
Contact: Vincent GUIGONIS, MD       vincent.guigonis@unilim.fr   
Contact: Claire BAHANS       claire.bahans@chu-limoges.fr   
Principal Investigator: Vincent GUIGONIS, MD         
Sub-Investigator: Anne-Laure FAUCHAIS, MD         
Sub-Investigator: Pascalle VERGNE-SALLE, MD         
Sub-Investigator: Didier MORIAU, MD         
CHU de MONTPELLIER Not yet recruiting
Montpellier, France, 34000
Contact: Alain LE QUELLEC, MD       a-lequellec@chu-montpellier.fr   
Principal Investigator: Alain LE QUELLEC, MD         
ApHp - hôpital Lariboisière Not yet recruiting
Paris, France, 75000
Contact: Korng EA, MD       korngea@yahoo.fr   
Principal Investigator: Korng EA, MD         
Sponsors and Collaborators
University Hospital, Limoges
Investigators
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Principal Investigator: Vincent GUIGONIS, MD University Hospital, Limoges

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Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT03582800     History of Changes
Other Study ID Numbers: I17004 (ITS-PILOT)
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: July 11, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Limoges:
Sodium thiosulfate
Ectopic calcification
Ectopic Ossification

Additional relevant MeSH terms:
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Sodium thiosulfate
Scleroderma, Systemic
Scleroderma, Diffuse
Calcinosis
Dermatomyositis
Cardiac Complexes, Premature
Connective Tissue Diseases
Skin Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Polymyositis
Myositis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Pathologic Processes
Antidotes
Protective Agents
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Chelating Agents