Clinical trial NCT03397810: Effect of Radiotherapy on ATTR Cardiac Amyloidosis : a Proof of Concept Study
Official title: Effect of Radiotherapy on ATTR Cardiac Amyloidosis : a Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amyloid Cardiomyopathy
Keywords: cardiac amyloidosis
radiotherapy
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2018-01-12
Enrollment: 36
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of the degree of amyloid
timeFrame: 12 weeks
Secondary outcomes:
measure: Safety and adverse event associated with cardiac low dose RT
timeFrame: 6 months
measure: Modification in echocardiographic global longitudinal strain
timeFrame: 6 months
measure: Modification in MRI extracellular volumes and T1 values
timeFrame: 12 weeks
measure: Modification in cardiac biomarker (ultrasensitive troponin T and BNP blood levels) features of cardiac amyloidosis
timeFrame: 6 months
measure: Modification of quality of life
timeFrame: 6 months
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospital
Study officials:
References: