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

Primary Purpose

Amyloid Cardiomyopathy

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

low dose radiotherapy

About this trial

This is an interventional treatment trial for Amyloid Cardiomyopathy focused on measuring cardiac amyloidosis, radiotherapy

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Geneva University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Singe arm

Arm Description

Subjects will receive a low dose radiotherapy focused to the heart

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Safety and adverse event associated with cardiac low dose RT

Assess the number of patients who report adverse events

Modification in echocardiographic global longitudinal strain

Assess intra-individual change in a quantitative measures

Modification in MRI extracellular volumes and T1 values

Assess intra-individual change in a quantitative measures

Modification in cardiac biomarker (ultrasensitive troponin T and BNP blood levels) features of cardiac amyloidosis

Assess intra-individual change in a quantitative measures

Modification of quality of life

The quality of life will be assessed by the SF-36 short form health survey quality of life scale

Full Information

NCT ID

NCT03397810

First Posted

January 4, 2018

Last Updated

May 7, 2021

Sponsor

Philippe Meyer

1. Study Identification

Unique Protocol Identification Number

NCT03397810

Brief Title

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

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Recruiting

Study Start Date

March 15, 2019 (Actual)

Primary Completion Date

February 28, 2026 (Anticipated)

Study Completion Date

February 28, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Philippe Meyer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyloid Cardiomyopathy

Keywords

cardiac amyloidosis, radiotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Singe arm

Arm Type

Experimental

Arm Description

Subjects will receive a low dose radiotherapy focused to the heart

Intervention Type

Radiation

Intervention Name(s)

low dose radiotherapy

Intervention Description

10 Gy in 5 fractions of 2 Gy on 5 consecutive days

Primary Outcome Measure Information:

Title

Assessment of the degree of amyloid

Description

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

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Safety and adverse event associated with cardiac low dose RT

Description

Assess the number of patients who report adverse events

Time Frame

6 months

Title

Modification in echocardiographic global longitudinal strain

Description

Assess intra-individual change in a quantitative measures

Time Frame

6 months

Title

Modification in MRI extracellular volumes and T1 values

Description

Assess intra-individual change in a quantitative measures

Time Frame

12 weeks

Title

Modification in cardiac biomarker (ultrasensitive troponin T and BNP blood levels) features of cardiac amyloidosis

Description

Assess intra-individual change in a quantitative measures

Time Frame

6 months

Title

Modification of quality of life

Description

The quality of life will be assessed by the SF-36 short form health survey quality of life scale

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

René Nkoulou, Dr.

Phone

+41 22 37 27 196

rene.nkoulou@hcuge.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Philippe Meyer, Dr.

Phone

+41 22 37 27 225

philippe.meyer@hcuge.ch

Facility Information:

Facility Name

Geneva University Hospital

City

Geneva

ZIP/Postal Code

1205

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

René Nkoulou, Dr.

rene.nkoulou@hcuge.ch

First Name & Middle Initial & Last Name & Degree

René Nkoulou

First Name & Middle Initial & Last Name & Degree

Philippe Meyer

First Name & Middle Initial & Last Name & Degree

Thomas Zillli

First Name & Middle Initial & Last Name & Degree

Valentina Garibotto

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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