Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02001961 |
| Other study ID # |
12CC23 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2014 |
| Est. completion date |
June 2015 |
Study information
| Verified date |
January 2022 |
| Source |
Great Ormond Street Hospital for Children NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This will be a cross-sectional, observational study.
Null hypothesis:
There is no difference in the amount of extracellular volume (ECV or scarring) in the hearts
of patients with heart failure as compared to control subjects.
Heart failure occurs when the heart muscle has become too weak to work properly. It is
associated with an increase in the amount of connective tissue (collagen) which replaces dead
heart muscle cells (scarring). Currently a biopsy of the muscle is the only way to measure
the amount of scarring. This is invasive and rarely done in children. Because of this, it is
difficult to measure the amount of scarring in a particular patient or disease process, which
is important for improving our understanding and treatment of the disease.
Cardiac magnetic resonance imaging (MRI) is a non-invasive imaging tool which is routinely
used to look at areas of local scarring in heart muscle. Because the scarring is so
widespread in paediatric patients, we have not been able to use this method previously. Now
new imaging techniques allow us to look at widespread scarring but these have not yet been
validated in children.
We plan to use late gadolinium enhancement (T1 mapping) to measure the amount of scarring in
patients with heart failure (we have evidence that their heart biopsies show increased
amounts of scar tissue) and children having MRI scans for other reasons. We will use measures
of function including echocardiography and 6 minute walk test to compare to the amount of
scarring. This will help us to know whether the amount of scarring will be clinically useful.
We will look at the amount of various proteins in the blood of patients and control subjects
which are related to the scarring and cell death processes. We already use blood tests to
monitor heart failure and these tests may help us to refine our testing and improve timing of
treatment (e.g. transplantation).
This study will help us to design further research in this field.
Description:
All patients will be under the care of Great Ormond Street Hospital.
Patient Groups:
There will be three main patient groups:
1. Heart Failure Patients (MRI Clinically indicated)
2. Heart Failure Patients (Voluntarily recruited from clinic)
1. 8-16 years of age
2. Non-GA only
3. Control subjects (Clinically indicated brain MRI with contrast)
Patient recruitment
We will include Great Ormond Street patients in this trial who are known to the heart failure
team because they have been diagnosed with DCM for at least 3 months. They will have an
established diagnosis of heart failure and will be under regular follow up. Where possible,
we will attempt to align the research study review date with that of the patient's regular
annual review.
We will include patients who are to have a cardiac MRI scan with contrast for clinical
reasons. These patients will be of any age and will have the scan under GA if appropriate, In
addition, we will recruit patients from heart failure clinic who are not due to have scans
for clinical reasons. These patients will be between 8-16 years to allow cooperation with the
MRI scan protocol without the need for general anaesthetic (GA).
Age-matched control patients will be those having routine MRI with contrast for non-cardiac
MRI scans. They will also have blood tests for cardiac biomarkers at the time of insertion of
the cannula for contrast injection. These will be patients identified as requiring gadolinium
contrast for neurological imaging. They will include patients who are awake and those sedated
or under GA. These patients will mainly be having routine brain MRI with contrast for
epilepsy.
Both groups will be fully consented.
Heart Failure Patients:
We will recruit patients being referred for cardiac MRI scanning for clinical reasons as well
as inviting patients to volunteer for an MRI. Patients who do not require a cardiac MRI for
clinical reasons will be over the age of 8 years to allow for cooperation with the MRI
without general anaesthesia. Patients under follow up by the heart failure team will be
contacted by their primary care consultant in the first instance to introduce the study and
invite the patient to participate. It will be made clear there is no obligation to join the
study and their treatment will be unaffected by their decision. They will be free to withdraw
consent at any time. The patients will be invited to phone the study coordinator (DP) to ask
questions, express willingness to participate or to decline. Non-responders will be sent one
further letter of invitation.
Control subjects:
Patients being referred to the MRI department at Great Ormond Street Hospital will be
identified once they have been allocated to a neurological MRI protocol with gadolinium
enhancement. The radiologist allocating the patient will contact the patients' primary
consultant to inform them about the study and request permission to contact the family. The
family will be contacted once permission has been given, first by phone and then information
sheets will be provided. The patients will be invited to phone the study coordinator (DP) to
ask questions, express willingness to participate or to decline. Non-responders will be sent
one further letter of invitation.
Travel costs will be reimbursed where these are incurred specifically for participation in
the study.
Consent:
Written, informed consent will be obtained from all participants if they choose to take part
in this study. Information sheets will also be provided to the patients' GP and their
cardiology physician, if they are under separate cardiology follow-up. Patients will be free
to withdraw at any time.
Risks & Burdens from the study protocol
The main risk arising from our study relates to the insertion of an IV line and
administration of a gadolinium-based contrast agent. Such contrast agents are widely used in
clinical practice and are extremely safe when administered within standard dosage guidelines.
There are, however, potential complications of allergic reaction and development of
Nephrogenic Systemic Fibrosis (NSF). Such allergic reactions are rare and when they occur,
the majority are mild.
To mitigate this risk we will exclude patients with a previous history of allergic response
to gadolinium-containing agents as well as those with a severe atopic history or history of
renal impairment. There are no known cases of NSF in patients with normal renal function(1).
We will measure renal function in all patients within 1 month of the study.
For patients being scanned specifically for the study, we will select patients over 8 years
of age, to avoid the need for general anaesthetic. We will attempt to select mainly patients
who require MRI scanning with contrast for clinical indications. The control group will only
consist of those having MRI for clinical indications. In this case, the only burden will be
increased time in the scanner of around 20 minutes to obtain the sequences required. Evidence
from our institution shows that the increased duration of general anaesthetic is not harmful
and does not lead to complications or adverse events.
We will obtain blood samples for serum bio-marker measurement and haematocrit at the time of
IV line insertion so this does not represent an additional intervention for the patient. We
will use local anaesthetic cream or spray as requested by the patient and will use play and
distraction techniques to minimise distress.
There are no potential adverse effects of a properly conducted transthoracic echocardiogram.
The 6 minute walk test will only be employed if the patient is able and willing to
participate.
There are no potential adverse effects of a properly conducted MRI scan. The magnetic field
and RF pulses are not known to cause any physical harm in properly selected subjects. Such
selection will involve careful screening of the patients' medical history for any surgery or
accidents that might have introduced metal to their bodies e.g. cerebral artery aneurysm
clips or a metal foreign body in an eye. This will require a review of the patient's notes
once consent has been given and a written checklist at the time of MRI scan. Such patients
are not scanned in standard clinical practice and would also be excluded from the study.
Therefore, there is no realistic potential for pain, discomfort, distress, inconvenience or
detrimental change to lifestyle anticipated for the participants from the MRI scan itself.
1. Dillman, J.R., J.H. Ellis, R.H. Cohan, P.J. Strouse, and S.C. Jan, Frequency and severity
of acute allergic-like reactions to gadolinium-containing i.v. contrast media in children and
adults. AJR Am J Roentgenol, 2007. 189(6): p. 1533-8.
Unexpected clinical findings
If new abnormalities or medical issues come to light as a result of the study investigations,
the patient's GP and hospital consultant will be informed. Medical follow-up of these issues
will be through the patient's usual medical carers.
