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

Amyloid Cardiomyopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03397810
• Other study ID #: 2017-00640
• Status: Recruiting
• Phase: N/A
• Start date: March 15, 2019
• Est. completion date: February 28, 2026

Study information

• Verified date: May 2021
• Source: University Hospital, Geneva
• Contact: René Nkoulou, Dr.
• Phone: +41 22 37 27 196
• Email: rene.nkoulou[@]hcuge.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: February 28, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy
• Amyloidosis
• Cardiomyopathies

Intervention

Radiation:
• low dose radiotherapy
10 Gy in 5 fractions of 2 Gy on 5 consecutive days

Locations

Country	Name	City	State
Switzerland	Geneva University Hospital	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Philippe Meyer

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Safety and adverse event associated with cardiac low dose RT	Assess the number of patients who report adverse events	6 months
Secondary	Modification in echocardiographic global longitudinal strain	Assess intra-individual change in a quantitative measures	6 months
Secondary	Modification in MRI extracellular volumes and T1 values	Assess intra-individual change in a quantitative measures	12 weeks
Secondary	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
Secondary	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