Pathophysiology of Dilated Cardiomyopathy

NCT02001961 | Withdrawn DMC

• 1 other identifier: 12CC23
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Dilated Cardiomyopathy

Keywords

Fibrosis; collagen metabolism; paediatric, dilated cardiomyopathy; biomarkers; T1 mapping; MRI

Outcome Measures

Primary Outcomes (1)

• Fibrosis

  Higher fibrosis score (ECV) in heart failure patients in comparison to control subjects

  6 months

Secondary Outcomes (2)

• Biomarkers

  6 months

• Disease Severity

  6 months

Study Arms (2)

Heart failure

Patients will be recruited from the heart failure clinic by their consultant. These will include patients who are due to have a MRI scan for clinical reasons and those who volunteer to participate. Voluntary subjects will be over 8 years.

Control

Control subjects will be identified after being referred for an MRI scan and being allocated to a non-cardiac MRI with gadolinium contrast.

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

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)

You may qualify if:

• Established diagnosis of DCM for 3 months
• Ability to cooperate with MRI scan without general anaesthesia (volunteers over 8 years), or any age if cardiac MRi clinically indicated
• Provides written, informed consent

You may not qualify if:

• Estimated GFR \<30mls/min
• Contraindication to MRI (see appendix 1)
• Chronic inflammation/ malignancy/ connective tissue disease
• Structural congenital heart disease/ previous cardiac surgery
• History of heart failure or congenital heart disease
• Contraindication to MRI (see below)
• Chronic inflammation/ malignancy/ connective tissue disease
• Previous malignancy
• Central nervous system aneurysm clips
• Implanted neural stimulator
• Implanted cardiac pacemaker or defibrillator
• Cochlear implant
• Ocular foreign body e.g. metal shavings
• Other implanted medical devices e.g. drug infusion ports
• Insulin pump

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead

Study Sites (1)

Great Ormond Street Hospital NHS Trust

London, WC1N 3JH, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma (\>400 UL) will be collected in heparinised tubes plasma will be extracted and the cell fraction discarded. Plasma will be stored at 80°C prior to transport on dry ice, via protected courier.

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Fibrosis

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Burch, MD

  Great Ormond Street Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2013
• First Posted: December 5, 2013
• Study Start: January 1, 2014
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2015
• Last Updated: January 20, 2022

Record last verified: 2022-01

Locations

GB (1)