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

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ClinicalTrials.gov Identifier: NCT03582800

Recruitment Status : Recruiting

First Posted : July 11, 2018

Last Update Posted : March 16, 2023

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View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

University Hospital, Limoges

Tracking Information

First Submitted Date ^ICMJE

June 13, 2018

First Posted Date ^ICMJE

July 11, 2018

Last Update Posted Date

March 16, 2023

Actual Study Start Date ^ICMJE

January 6, 2020

Estimated Primary Completion Date

March 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

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.

Change History

Current Secondary Outcome Measures ^ICMJE

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

Original Secondary Outcome Measures ^ICMJE

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

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Subcutaneous Injection of Sodium Thiosulfate for Ectopic Calcifications or Ossifications. A Pilot Study

Official Title ^ICMJE

Subcutaneous Injection of Sodium Thiosulfate for Ectopic Calcifications or Ossifications. A Pilot Study

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).

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

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

Condition ^ICMJE

Systemic Sclerosis
Dermatomyositis
iPPSD2

Intervention ^ICMJE

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.

Study Arms ^ICMJE

Experimental: Treated

M0-M6: run-in phase (control) M6-M12: STS treatment phase

Intervention: Drug: STS

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

March 2023

Estimated Primary Completion Date

March 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

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

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

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

Listed Location Countries ^ICMJE

France

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03582800

Other Study ID Numbers ^ICMJE

I17004 (ITS-PILOT)

Has Data Monitoring Committee

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

University Hospital, Limoges

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

University Hospital, Limoges

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Vincent GUIGONIS, MD

University Hospital, Limoges

PRS Account

University Hospital, Limoges

Verification Date

March 2023

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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