Effect of Radiotherapy on ATTR Cardiac Amyloidosis : a Proof of Concept Study

Study Overview
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Brief Summary
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Cardiac amyloidosis is responsible for significant morbidity associated with heart failure, and carries a poor prognosis. Currently there are very limited treatment options for this condition. Radiotherapy has been used successfully to treat amyloidosis elsewhere in the body, however has not been tried in cardiac amyloidosis. Therefore this study aims to assess the effect of radiotherapy on cardiac amyloidosis, to evaluate whether it can successfully reduce the burden of amyloid deposits in the myocardium as assessed by 18F-Amyloid PET.

Detailed Description
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The intervention will involve administration of external beam radiotherapy (5 fractions of 2Gy) focused to the heart. Measurements of effect will be assessed at 12 weeks by: Amyloid PET Cardiac MRI with administration of gadolinium and ultrasound A blood venous sample (cardiac biomarkers) Quality of life assessments

Official Title
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Effect of Radiotherapy on ATTR Cardiac Amyloidosis : a Proof of Concept Study

Conditions
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Amyloid Cardiomyopathy

Intervention / Treatment
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* Radiation: low dose radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >65 y.o. Dyspnoea on exertion (NYHA II or more). Stable elevated cardiac enzymes (ultra sensitive Troponin T > 14 ng/L on consecutive sampling or BNP > 100pg/mL) A positive 99mTc-DPD cardiac scintigraphy (Grade 2 and 3) suggesting an ATTR or wt amyloidosis. Additional imaging also compatible with cardiac amyloidosis (cardiac ultrasound showing basal to apical longitudinal strain gradient and magnetic resonance imaging with elevated T1 value or extracellular volume). Compliance with the informed consent as attested by its signature. Positive baseline 18F-Florbetapir imaging, as assessed visually and quantitatively by a Tissue to Background Ratio > 1.45 Exclusion Criteria: Positive serum protein immunoelectrophoresis with monoclonal gammapathy. Previous external beam radiotherapy including the chest. Claustrophobia Presence of internal non-MR compatible devices Creatinine glomerular filtration rate < 30 ml/min Oncologic disease (excluding skin cancer) active or in remission from less than 5 years

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Singe arm<br>Subjects will receive a low dose radiotherapy focused to the heart | Radiation: low dose radiotherapy<br>* 10 Gy in 5 fractions of 2 Gy on 5 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the degree of amyloid | Assess intra-individual change in a quantitative measure of amyloid deposits on 18F-Amyloid (Standard Uptake Value ratio) SUVR between amyloid PET scans before and after low dose RT | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and adverse event associated with cardiac low dose RT | Assess the number of patients who report adverse events | 6 months | 
| Modification in echocardiographic global longitudinal strain | Assess intra-individual change in a quantitative measures | 6 months | 
| Modification in MRI extracellular volumes and T1 values | Assess intra-individual change in a quantitative measures | 12 weeks | 
| Modification in cardiac biomarker (ultrasensitive troponin T and BNP blood levels) features of cardiac amyloidosis | Assess intra-individual change in a quantitative measures | 6 months | 
| Modification of quality of life | The quality of life will be assessed by the SF-36 short form health survey quality of life scale | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac amyloidosis, radiotherapy