Trial record 2 of 7 for:    Open Studies | "Pneumoconiosis"

An Epidemiological Study to Assess Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study) (MACS1631)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01736540
First received: November 26, 2012
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

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 will be 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 is to assess the prevalence and severity of cardiac and liver siderosis in patients with transfusional siderosis. This study will also aim to establish possible correlations between cardiac and liver iron levels with clinical effects in patients with different transfusion-dependent anaemias. Patients will be eligible for enrollment irrespective of receiving chelation therapy or not (and irrespective of the chelating agent used).


Condition Intervention
Thalassemia, Non-transfusion Dependent Thalassemia, Myelodysplastic Syndromes, Myelofibrosis, Other Anemia
Radiation: Single arm MRI test

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Epidemiological Study to Assess the Prevalence of Iron Overload Using MRI in Patients With Transfusional Siderosis (TIMES Study)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Prevalence and severity of liver and cardiac iron overload in patients with transfusional siderosis (MDS, thalassaemia major and other anaemias). [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    Hepatic and cardiac iron overload in patients with transfusional siderosis (MDS, thalassaemia major and other anaemias) will be measured using MRI to measure both liver and cardiac iron loading (R2 by FerriScan and T2*, respectively). Values will be compared to published thresholds of iron overload to determine severity of transfusion siderosis in the patient population studied.


Secondary Outcome Measures:
  • Measurement of iron overload due to transfusion therapy comparing chelation-naïve and chelation-treated patient subgroups. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    The severity of iron overload due to transfusion therapy will be assessed based on chelation status of each patient (i.e. chelation-naïve and chelation-treated patient subgroups).

  • Levels of cardiac and liver siderosis in different populations of patients requiring regular blood transfusions (e.g. thalassaemia major vs. NTDT, thalassaemia major vs. MDS). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Levels of cardiac and liver siderosis will be compared between patient subgroups, according to their primary diagnosis leading to anaemia (e.g. thalassaemia major vs. NTDT, thalassaemia major vs. MDS).

  • Relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    The relationship between serum ferritin, cardiac and liver iron with cardiac and hepatic events will be assessed all patient subgroups.

  • Relationship between BMS and cardiac T2*. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Relationship between BMS and cardiac T2* will be assessed comparing all patient groups.

  • Haematologic parameters and transfusion requirement in patients with acquired anaemias with history of receiving chelation therapy. [ Time Frame: 12 months - retrospective ] [ Designated as safety issue: No ]
    haematologic parameters and transfusion requirement in patients with acquired anaemias with history of receiving chelation therapy will be assessed, in order to evaluate possible impact of chelation on transfusion independence.

  • Quality of life and different disease states, levels of iron overload and different chelation regimens. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Quality of life will be assessed comparing different disease states, levels of iron overload and different chelation regimens.

  • Adherence of patients according to different chelation regimens. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Adherence of patients according to different chelation regimens (adherence questionnaire will only be recorded for patients receiving chelating agents).

  • Treatment decisions based on MRI results. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Treatment decisions will be recorded after the investigator evaluates the MRI results, in order to assess the impact of such diagnostic test on the overall clinical management of patients with iron overload.


Estimated Enrollment: 250
Study Start Date: February 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single arm MRI test
All patients will be subjected to the non-invasive hepatic and cardiac MRI test to measure iron overload.
Radiation: Single arm MRI test
All patients will be subjected to the non-invasive hepatic and cardiac MRI test to measure iron overload.

Detailed Description:

This study is designed to collect information about a large cohort of patients with anaemias including MDS, aplastic anemia, Diamond-Blackfan, myeloproliferative disorder, as well as haemoglobinopathies (e.g. thalassaemia major, SCD) or other anaemias requiring chronic red blood cell transfusions.

Clinical data will be collected retrospectively (if available), unless specified by this protocol (e.g. serum ferritin within less than one month prior to enrollment). All assessments required for this protocol should be performed after the patient informed consent is signed. The data will be gathered by all study centers and will be combined in one central database.

Data will be recorded using an electronic case report form (eCRF) at each study site. Adverse events and serious adverse events will be recorded for all patients from the date of signed patient informed consent until the MRI tests are performed.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736540

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Australia, New South Wales
Novartis Investigative Site Active, not recruiting
Camperdown, New South Wales, Australia, 2050
Novartis Investigative Site Not yet recruiting
Liverpool, New South Wales, Australia, 2170
Novartis Investigative Site Recruiting
St Leonards, New South Wales, Australia, 2065
Novartis Investigative Site Not yet recruiting
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Novartis Investigative Site Recruiting
South Brisbane, Queensland, Australia, 4101
Novartis Investigative Site Recruiting
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Novartis Investigative Site Recruiting
Adelaide, South Australia, Australia, 5000
Novartis Investigative Site Recruiting
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Novartis Investigative Site Recruiting
East Bentleigh, Victoria, Australia, 3165
Australia, Western Australia
Novartis Investigative Site Not yet recruiting
Nedlands, Western Australia, Australia, 6009
Novartis Investigative Site Recruiting
Perth, Western Australia, Australia, 6000
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01736540     History of Changes
Other Study ID Numbers: CICL670AAU05
Study First Received: November 26, 2012
Last Updated: May 1, 2014
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration

Additional relevant MeSH terms:
Pneumoconiosis
Primary Myelofibrosis
Anemia
Myelodysplastic Syndromes
Preleukemia
Siderosis
Thalassemia
Iron Overload
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Lung Injury
Occupational Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014