Improvement of MRI assessed cerebral Perfusion and oxygenation by luspatercept-induced Anemia Correction in non-transfusion dependent Thalassemia
- Conditions
- on-transfusion dependent beta-thalassmiaMedDRA version: 20.0Level: LLTClassification code: 10074356Term: Non-transfusion dependent thalassemia Class: 10010331MedDRA version: 20.1Level: LLTClassification code: 10054660Term: Thalassemia beta Class: 10010331Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2023-504908-28-01
- Lead Sponsor
- Amsterdam UMC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
NTDT beta-thalassemia, Baseline Hb level of = 10.0 based on the mean Hb level 24 weeks before initiation of luspatercept g/dL, = 18 years of age, = 5 RBC units transfused in the 24 weeks prior to inclusion in the study, Participants, who if female and of childbearing potential, are using highly effective methods of contraception from study start to 30 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 30 days after the last dose of study drug., Participant has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each participant; the participant’s legal representative or legal guardian, and the participant’s assent must be obtained).
No informed consent has been given., Contra-indication for MRI or acetazolamide, Female who is breast feeding or pregnant., Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4 × ULN., Severe renal dysfunction (estimated glomerular filtration rate <30mL/min)., History of malignancy within the past 2 years prior to participation requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)., History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent, including but not limited to the following: 1. Unstable angina pectoris or myocardial infarction or elective coronary intervention. 2. Congestive heart failure requiring hospitalization. 3. Uncontrolled clinically significant arrhythmias., Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device)., Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess whether luspatercept can improve the cerebral oxygen metabolism (CMRO2) in patients with non-transfusion-dependent thalassemia (NTDT) with Hb increase of = 1 g/dL;Secondary Objective: To assess the effect of luspatercept treatment on CMRO2 in NTDT patients, To assess the effect of luspatercept treatment on cerebral blood flow (CBF) in patients with NTDT, To assess the effect of luspatercept treatment on processing speed as measure of neurocognitive impairment, To assess the effect of luspatercept treatment on cardiac parameters of pulmonary hypertension (NTproBNP and TRV);Primary end point(s): Cerebral metabolic rate of oxygen (CMRO2) is measured by MRI technique by T2 relaxation under spin tagging (TRUST).
- Secondary Outcome Measures
Name Time Method Secondary end point(s):CBF will be measured by time-encoded CASL.;Secondary end point(s):Transthoracic echocardiography will be performed in order to assess the TRV. These assessments will be performed at baseline, and 27 weeks later. If transthoracic echocardiography to assess the TRV has been performed within one year before the first study visit (prior to inclusion of the patient in the study), that previously performed transthoracic echocardiography will be used as baseline transthoracic echocardiography for this study.;Secondary end point(s):General laboratory analysis will be performed on venous blood samples at baseline, every three weeks after start of treatment until week 27. Analysis consists of hemoglobin, leukocyte and platelet count, renal and liver assessments and NT-proBNP.