TRANSCEND

The TRANSCEND study will include patients seen at the NAC with all types of ATTR amyloidosis.

ATTR amyloidosis: filling in the gaps in our knowledge

Hereditary ATTR amyloidosis

The FAP World Transplant Registry (FAP WTR) was established in 1995, in order to compile data on survival of patients who undergo liver transplantation for hereditary ATTR amyloidosis (previously known as FAP) and to determine the optimal time for liver transplantation. Most patients worldwide who have undergone liver transplantation for hereditary ATTR amyloidosis carry a single TTR mutation, Val30Met, which is rare in the UK. There is a relative lack of data on the natural history of hereditary ATTR amyloidosis in association with the other disease-causing TTR gene mutations.

We now know that liver transplantation does not prevent continued build-up of ATTR amyloid in the heart. There is a need for careful cardiac follow-up of patients who have undergone liver transplantation for hereditary ATTR amyloidosis, to enhance our understanding of this process.

'Wild-type' ATTR amyloidosis and amyloid cardiomyopathy

Newly available cardiac imaging techniques (cardiac magnetic resonance imaging and DPD scintigraphy) have resulted in greatly increased diagnoses of cardiac ATTR amyloidosis. There has been a 40-fold increase in the number of referrals of patients to the NAC with ‘wild-type’ ATTR amyloidosis over the past decade.

ATTR amyloidosis may be a relatively common cause of heart failure in the elderly. There is a need to follow these patients systematically in order to learn about the natural history of this emerging condition, and to increase awareness of the condition throughout the UK.

Quality of life (QOL)

At present there are no standard, accepted measures of QOL for ATTR amyloidosis. TRANSCEND aims to establish and validate such measures, by following QOL throughout the disease course. QOL measures will also be important when assessing the effects of new drugs for ATTR amyloidosis.

New treatments

There are several drugs for ATTR amyloidosis currently in various stages of development. To arrange future clinical trials of these drugs, and to assess their effects, there is an urgent need for increased understanding of the natural course of both cardiac and nervous system disease caused by amyloid.

What the study involves for patients

Patients will undergo all the standard assessments that are usually performed at the NAC. There are no additional tests performed on patients (it is an observational study); the important difference is that we will systematically and carefully record all data in a special database for analysis. These include:

1. Baseline assessment evaluation of the medical history, neurological and cardiac assessment, physical examination, blood tests, specialised cardiac imaging tests, functional tests and QOL assessment.
2. Ongoing assessments include recording hospital admissions and changes in drug dosages. A member of the NAC study team will conduct a telephone consultation with any patient who has been admitted to their local hospital.
3. Annual review at the NAC including weight, blood tests, specialised cardiac imaging (echocardiography and cardiac MRI scan), functional tests such as 6 minute walking distance and performance status assessment, neuropathy scoring (where relevant), and QOL assessment.

All these assessments are routinely undertaken at the NAC as part of standard clinical care.

Who can take part in the trial

All patients diagnosed with ATTR amyloidosis assessed at the NAC are eligible for the trial if they are capable of providing written, informed consent..

Study aims

The TRANSCEND study aims to do for ATTR amyloidosis what the ALchemy study has done for AL amyloidosis.

The ALchemy study, which has been running since 2009, follows all patients diagnosed with systemic AL amyloidosis at the NAC. The data gathered has contributed greatly to our knowledge and understanding of the full spectrum of this disease in the UK. Some of our standard clinical management protocols have been adjusted in the light of the information gathered in this study.

The TRANSCEND study aims to achieve similar goals for ATTR amyloidosis by following all patients diagnosed with this condition at the NAC. It is a prospective study, which means that patients will be followed from the time of diagnosis. It is observational, meaning that there are no additional interventions for patients and the goal is systematic and careful data collection. 

As discussed above, there have not previously been large scale trials following patients with all types of ATTR amyloidosis. Our understanding of the condition is rapidly evolving, with a significant recent increase in the frequency with which ‘wild-type’ ATTR amyloidosis is diagnosed. The only way we can fill in the gaps in our knowledge of this condition is by carefully following large numbers of patients over time.

The study itself will not involve any alterations in standard clinical practice. However, it is likely that understanding gained from this study may eventually influence and improve clinical management of patients.

Timing

The TRANSCEND study is ongoing.