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

Not Applicable

Recruiting

• Conditions: Amyloid Cardiomyopathy
• Interventions: Radiation: low dose radiotherapy

• Registration Number: NCT03397810
• Lead Sponsor: Philippe Meyer

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2018-01-04
• Study First Submitted QC: 2018-01-11
• Study First Posted: 2018-01-12
• Study Start: 2019-03-15
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-07
• Last Update Posted: 2021-05-11
• Primary Completion: 2026-02-28
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Singe arm	low dose radiotherapy	Subjects will receive a low dose radiotherapy focused to the heart

Primary Outcome Measures

Name	Time	Method
Assessment of the degree of amyloid	12 weeks	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Geneva University Hospital; 🇨🇭 Geneva, Switzerland