An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)
Condition: Thalassemia, Non-transfusional-dependent Thalassemia (NTDT), Myeloplastic Dysplasia (MDS), Other Anemia
MeSH terms: Siderosis; Thalassemia; Iron Overload
Intervention: MRI scan
Intervention description: MRI was used to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively).
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 243.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: iron overload, liver iron concentration (LIC), cardiac siderosis, transfusional siderosis, magnetic resonance imaging (MRI)

Summary:

      Iron, one of the most common elements in nature and the most abundant transition metal in the
      body, is readily capable of accepting and donating electrons. This capability makes iron a
      useful component of various, essential biochemical processes. Despite the essential role of
      iron, the excess of iron is toxic to the human body. It is critical for the human body to
      maintain iron balance, since humans have no physiologic mechanism for actively removing iron
      from the body.

      The development of iron overload occurs when iron intake exceeds the body's capacity to
      safely store the iron in the liver, which is the primary store for iron. Long-term
      transfusion therapy, a life-giving treatment for patients with intractable chronic anemia is
      currently the most frequent cause of secondary iron overload.

      The mounting evidence regarding the mortality and morbidity due to chronic iron overload in
      transfusion dependent anaemias has led to the establishment of guidelines that aim the
      improvement of patient outcomes. Further prospective studies are warranted in order to assess
      the impact of iron overload in patients with acquired anaemias.

      In this study, non-invasive R2- and T2*-MRI techniques were applied to the liver and the
      heart, respectively, to complement the primary variable (serum ferritin) assessed in patients
      with various transfusion-dependent anaemias. The main objective of this study was to assess
      the prevalence and severity of cardiac and liver siderosis in patients with transfusional
      siderosis. This study was also aim to establish possible correlations between cardiac and
      liver iron levels with clinical effects in patients with different transfusion-dependent
      anaemias. Patients were eligible for enrollment irrespective of receiving chelation therapy
      or not (and irrespective of the chelating agent used).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years

          -  Confirmed clinical diagnosis of one of the following disease states: 1.
             Myelodysplastic syndromes, 2. Thalassaemia major, 3.Other anaemias (e.g. NTDT, SCD,
             Diamond-Blackfan anaemia, aplastic anaemia, myeloproliferative disease)

          -  Lifetime history of at least 20 units of red blood cell transfusions AND serum
             ferritin level > 500 ng/ml; patients with NTDT are not required to have a minimum of
             20 units of red blood cell transfusions, but must have serum ferritin level > 300
             ng/ml (serum ferritin for all patients must be measured up to 1 month prior to
             enrollment)

          -  Written informed consent obtained prior to any procedure required by this protocol

        Exclusion Criteria:

        Any condition that does not allow the MRI test to be performed: 1. Cardiac pacemaker, 2.
        Ferromagnetic metal implants other than those approved as safe for use in MR scanners
        (Example: some types of aneurysm clips, shrapnel), 3. Obesity (exceeding the equipment
        limits), 4. Patients who are claustrophobic to MR Women who are pregnant Unwillingness or
        being unable to give consent