Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02009345 |
| Other study ID # |
FH Canada |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 2013 |
| Est. completion date |
November 2028 |
Study information
| Verified date |
October 2023 |
| Source |
McGill University Health Centre/Research Institute of the McGill University Health Centre |
| Contact |
Isabelle Ruel, PhD |
| Phone |
514-934-1934 |
| Email |
isabelle.ruel[@]mail.mcgill.ca |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Familial hypercholesterolemia (FH) is the most frequent genetic lipoprotein disorder
associated with premature CAD. In Canada, the burden of disease is estimated to be
approximately 83,500 patients. The goal of this initiative is to create a registry of
subjects with FH across Canada. Rare diseases of lipoprotein metabolism are also included.
Using a "hub and spoke" model, the registry extends in various communities to link primary
care physicians with provincial academic centers. The registry includes clinical, biochemical
and demographic information. Specimens (plasma/serum and DNA) are collected for biobanking.
The "local" portion of the registry is available for clinicians to manage patient care, and
identify relatives for screening and treatment (cascade screening). The Canada-wide registry,
which is completely anonymized, will be made available to provide advice to general
practitioners and to support collaborative studies in biomedical, clinical, health outcomes
and health economics research. The data extracted for the provincial portion of the database
will allow administrative database research that will provide important information to key
stakeholders and permit allocation of resources. It will also allow a sound and uniform
rationale for the use of novel therapeutic agents and provide expert advice to regulatory
agencies. At the Canadian level, the database will allow clinicians and researchers to
determine the burden of disease and the long-term effects of treatment. Through the creation
of a Canada-wide network of academic clinics, integrating lipid specialists, endocrinologists
and cardiologists, the Canadian FH registry will lead to significant benefits for FH
patients, clinicians and researchers, biopharmaceutical industry and government.
Description:
Familial hypercholesterolemia (FH) is a genetic lipoprotein disorder characterized by
elevations in low-density lipoprotein cholesterol (LDL-C) >95th percentile for age and
gender. Affected individuals may show clinical manifestations (xanthomas, xanthelasmas and
premature arcus corneus) although these manifestations are seen less frequently with early
diagnosis and treatment. Untreated, FH will lead to atherosclerotic cardiovascular disease
(CVD), primarily coronary artery disease (CAD). There are at least three accepted definitions
for FH, based on absolute LDL-C levels (MedPed criteria), the Simon-Broome criteria include a
fixed cut-point for LDL-C, the presence of DNA mutations and xanthomas and the FH Dutch
Criteria (the Netherlands).
There are well-developed FH Registries in the Netherlands, United Kingdom, Spain, France, and
the US, through the newly established US FH Foundation. In the United Kingdom, a report on
the economic advantages of treating FH revealed that lipid-lowering statin therapy would lead
to 101 fewer cardiovascular deaths/1000 patients with FH given treatment. The cost saving
from cardiovascular events is estimated at over $CAN 592 million in the UK if all relatives
of index cases were identified and treated, compared with no treatment given. This cascade
testing strategy has been successfully applied in the Netherlands in families of FH probands
with a detected mutation, thus allowing statin treatment of family members at risk of early
coronary heart disease.
In Canada, the burden of disease is estimated to be approximately 120,000 patients, based on
an allele frequency of LDL-R mutations of 1/311. In the province of Quebec, the allele
frequency is approximately 1/270 and the number of affected subjects is approximately 29,000.
Left untreated, FH men develop cardiovascular disease (CVD) in the third decade of life and
women, in the fourth decade. When identified and treated early, life expectancy is normal.
The purpose of this initiative is to create a registry of subjects with FH across Canada
designed to identify subjects with FH and to improve health and healthcare delivery. Rare
diseases of lipoprotein metabolism (orphan diseases) are also included (SMASH registry;
Systems and Molecular Approach of Severe Hyperlipidemia). This registry includes clinical,
biochemical and demographic information. Specimens (plasma/serum and DNA) are collected for
biobanking. The "local" portion of the registry is available for clinicians to manage patient
care, and identify relatives for screening and treatment (cascade screening). The Canada-wide
registry, which is completely anonymized, will be made available to provide advice to general
practitioners and to support collaborative studies in biomedical, clinical, health outcomes
and health economics research. Access to anonymized data from the registry will be given to
researchers, clinicians, biopharmaceutical industry and government by peer-reviewed process.
The Mission of the Canadian FH Registry is to bring together a multi-disciplinary group of
physicians, basic and clinical researchers to improve the delivery of care to patients with
severe lipoprotein disorders, especially FH, and to foster collaborative research. Our Vision
is to create a Canada-wide network of academic clinics, integrating lipid specialists,
endocrinologists and cardiologists to treat patients with the highest standard of care and to
create a collaborative research environment. Using a "hub and spoke" model, the registry
extends in various communities to link primary care physicians with provincial academic
centers. The Goals are to improve care to patients with FH and to reduce cardiovascular
disease in this population at high risk.
Given the wide geographic distribution of patients with FH, we provide a "hub and spoke"
model specialized care. The hubs are based in each province in centers recognized at the
national level for their expertise in lipoprotein disorders and with advanced laboratory
facilities (medical biochemistry, specialized assays, ultracentrifugation, genetic testing).
Radiating from these centers are clinics that treat patients with FH. We propose a three-tier
registry (local, provincial and Canada-wide). The local database is nominative, used solely
by the clinic or center and contain the information obtained by the local investigators and
used for clinical purposes. The provincial database is de-identified and will be used to
generate province-specific health outcomes, resource utilization, health economics and
comparative epidemiological/genetic/clinical features across provinces. The Canadian database
is also anonymous and will serve to generate country-wide statistics, public awareness and
research collaborations.
All procedures related to the FH registry are standardized. The various steps associated with
the inclusion of patients within the FH Registry are the following: subject with high LDL-C,
secondary causes ruled out, FH Criteria satisfied, consent form signed, clinical evaluation,
baseline lipid profile, demographic info, family history, longitudinal follow-up (annual data
capture). If a patient has a family history of FH, then we start cascade screening. If the FH
criteria are not satisfied at the beginning of the study then the patient is being asked to
enter in the SMASH registry for other severe disorders of the lipid metabolism. DNA isolation
and banking is being performed at individual sites (locally) only. Central biobanking is not
possible for now. The question form mainly includes data on the familial history of elevated
cholesterol levels and CVD, the patient's medical and surgical history, the physical signs of
FH, and the patient's medication profile.
The James Hogg Research Centre at St-Paul's Hospital, UBC, Vancouver is providing the
iCAPTURE platform to be used to capture the data from the FH Canada Registry. This center
maintains multi-level security for all database and computer systems. The security measures
include physical entry to the compute facility and access to the systems within the facility.
The server facility is a single entry electronically card accessible room that is equipped
with video surveillance. Entry is accessible to the authorized personnel only. All hard drive
storage is maintained on a SAN which has data encryption. The database utilizes an Oracle
backend and is firewalled and maintained in a separate non public network, and it is FDA (US
Food and Drug administration), Health Canada, PHIA (Personal Health Information Act) and
PIPEDA (Canada Personal Information Protection and Electronic Documents Act) compliant. All
data is de-identified based on role based access and redacted automatically within the
database. All user access is logged. A unique identifier is assigned to each patient entered
in the database, and parents, siblings and all first-degree relatives of each subject is
entered with a distinct identifier. Completely anonymous data, without any identifier -such
as hospital ID number, date of birth, family relationships will be made available to
researchers, policy makers, governments and industry on a per need basis after a submission
of a written request and approval by the Scientific Board in consultation with the Advisory
Board.
Potential benefits Patients. Patients will have access to expert care in the field of
lipoprotein disorders and CVD prevention. In many cases, optimal treatment of severe
hypercholesterolemia may be best provided by experts in the field. They will have access to
on-going clinical trials and to novel therapies. Furthermore, individual patients will be
offered family screening to identify affected members who would benefit from early diagnosis
and treatment. The identification of new FH cases by cascade screening proves to be both
cost-effective and aligns with the aim of providing personalized medicine for patients with
severe lipoprotein disorders.
Clinicians. The registry will provide the local (i.e. clinic or hospital) framework to
diagnose patients according to accepted international criteria for FH, to follow the subjects
in time and to perform cascade screening (first, second and third-degree relatives), a
cost-effective strategy to screen potentially affected subjects. The registry will also link
clinicians into a network of specialized clinics that favor collaborative
investigator-initiated research and participation in multi-center studies. The availability
of biobanking will allow the storage of plasma/serum and DNA for future research.
Biomedical researchers. The identification of novel genes for FH and other rare lipoprotein
disorders has led to a better understanding of metabolic pathways and eventually the
potential for novel therapeutic targets. In addition, gene-gene and gene-environment
interactions research may shed light on mechanisms of disease. clinical-scientists will have
the opportunity to develop investigator-initiated research, using the pan-Canadian registry
and biobanking resources as a platform. Researchers in health outcomes and health economics,
social, gender and ethnic research will have access to the database in collaboration with
provincial administrative databases.
Biopharmaceutical Industry. The biopharmaceutical industry will have access to a group of
lipid experts across Canada, with links internationally, a harmonized database for subjects
with FH and rare lipoprotein disorders. They will have access to a network of established
clinics with a unified database. Access to the registry database will be provided after
review of the intended research. This data will be important in determining health economics.
Government. This initiative will allow the development of clinical practice guidelines, to
determine resource allocation according to need, the identification of rare (orphan disease)
lipoprotein disorders requiring specific techniques, such as extracorporeal LDL filtration
for homozygous FH. The initiative will allow the framework to set-up collaborative research
under the peer-review system (HSFC, CIHR). Health outcomes and health economic studies will
allow resource allocation and quality control. Finally centralized genetic testing would
provide molecular diagnostics in a cost-effective manner, when required. This initiative will
dovetail with the CIHR C-CHANGE initiative concerning the harmonization of cardiovascular
preventive guidelines in Canada. To data, we are the only country with harmonized CVD
prevention guidelines.
Knowledge translation and training. Individual academic institutions with a strong biomedical
research commitment will offer undergraduate and graduate-level training in the field of
lipid and lipoproteins within a country-wide collaborative research environment. Several
centers will offer post-doctoral fellowships for clinicians and PhDs in lipoprotein
metabolism, health outcomes and health economics research. This training of highly qualified
personnel is expected to contribute to the academic and economic engine of the country. A
formal training course, aligned with the National Lipid Association, will provide
certification on the treatment of lipoprotein disorders. The establishment of clinical
practice guidelines for adult and pediatric patients will enable clinicians to hone their
clinical practice to the highest standard. By using well established conferences across
Canada, the aim will be to integrate novel knowledge into the yearly conference programs
across Canada and to disseminate this information to practicing physicians and health care
professionals.
