Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582800
Recruitment Status : Not yet recruiting
First Posted : July 11, 2018
Last Update Posted : October 15, 2019
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 October 15, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2018)
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 Same as current
Change History Complete list of historical versions of study NCT03582800 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • 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
 (submitted: June 27, 2018)
  • 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 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 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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 27, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2022   (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 No
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 No
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
Responsible Party University Hospital, Limoges
Study Sponsor  ICMJE University Hospital, Limoges
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vincent GUIGONIS, MD University Hospital, Limoges
PRS Account University Hospital, Limoges
Verification Date October 2019

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