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

May 7, 2021 updated by: Philippe Meyer
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.

Study Overview

Status

Recruiting

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Geneva, Switzerland, 1205
        • Recruiting
        • Geneva University Hospital
        • Contact:
        • Principal Investigator:
          • René Nkoulou
        • Sub-Investigator:
          • Philippe Meyer
        • Sub-Investigator:
          • Thomas Zillli
        • Sub-Investigator:
          • Valentina Garibotto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

63 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the degree of amyloid
Time Frame: 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
12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2019

Primary Completion (Anticipated)

February 28, 2026

Study Completion (Anticipated)

February 28, 2026

Study Registration Dates

First Submitted

January 4, 2018

First Submitted That Met QC Criteria

January 11, 2018

First Posted (Actual)

January 12, 2018

Study Record Updates

Last Update Posted (Actual)

May 11, 2021

Last Update Submitted That Met QC Criteria

May 7, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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