Keywords:Huntington's Disease (HD) , Observational , Prospective Registry , Multi-national , Mutli-center
Enroll-HD is an observational, open-ended, prospective, multi-national, multi-centre study without experimental treatment.
Objective 1: To improve the understanding of the dynamic phenotypic spectrum and the disease mechanisms of HD by:
a. collecting natural history data covering the cognitive, behavioral and motor domains permitting estimates of rates of progression in HD and allowing insights into the neurobiology of HD,
b. collecting data and biologic samples to identify genetic and environmental factors influencing and/or modifying the HD phenotype and disease progression, and
c. promoting interrogatory studies that may provide clues to the pathogenesis of HD.
Objective 2: To promote the development of evidence-based guidelines to inform clinical decision making and improve health outcomes for the participant/family unit by:
a. assisting in the identification of beneficial interventions (clinical, pharmaco-therapeutic, non-pharmacologic),
b. facilitating the dissemination and implementation of currently proposed best clinical practices,
c. providing a platform for conducting outcome research, and
d. promoting exploratory data analysis projects that may identify processes to further improve the healthcare of affected individuals and their families.
Objective 3: To provide a platform to support the design and conduct of clinical trials by:
a. providing a resource to identify, develop and qualify novel assessment tools, clinical endpoints and biomarkers,
b. collecting longitudinal data to inform disease modeling studies, and
c. facilitating the identification of potential trial participants informing the selection of potential trial participants using data to estimate and quantify slopes/rates of disease progression (providing “run-in” data).
To achieve these objectives suitably de-identified and coded clinical information and biological samples collected from study participants will be made available to investigators for research purposes in accordance with procedures adopted by the steering committee.
Individuals eligible to participate in Enroll-HD are classified into two major categories:
1. Carriers: This group comprises the primary study population and consists of individuals who carry the HD gene expansion mutation.
2. Controls: This group comprises the comparator study population and consists of individuals who do not carry the HD expansion mutation. These two major categories can be further subdivided into six different subgroups of eligible individuals:
a. Manifest/Motor-manifest HD: Carriers with clinical features that are regarded in the opinion of the investigator as diagnostic of HD.
b. Pre-Manifest/-Motor-manifest HD: Carriers without clinical features regarded as diagnostic of HD.
c. Genotype Unknown: This group includes a first or second degree relative, i.e., related by blood to a carrier, who has not undergone predictive testing for HD and therefore has an undetermined carrier status.
d. Genotype Negative: This group includes a first or second degree relative, i.e., related by blood to a carrier, who has undergone predictive testing for HD and is known not to carry the HD expansion mutation.
e. Family Control: Family members or individuals not related by blood to carriers (e.g., spouses, partners, caregivers).
f. Community Controls: Individuals unrelated to HD carriers who did not grow up in a family affected by HD. Data collected from community controls will be used for generation of normative data for sub-studies.
Participant status will be captured in the study database using 2 variables: 1) Investigator Determined Status: this will be based on clinical signs and symptoms and genotyping performed as part of medical care, and will be updated at every visit and 2) Research Genotyping Status: this will be based on genotyping conducted as part of Enroll-HD study procedures. Based on research genotyping, participants will be reclassified under this variable from Genotype Unknown to ‘Carriers' or 'Controls’. Investigators and participants will be blinded to this reclassification.
1. Individuals who do not meet inclusion criteria,
2. Individuals with choreic movement disorders in the context of a negative test for the HD gene mutation.
3. For Community Controls: those individuals with a major central nervous system disorder will be excluded (e.g. stroke, Parkinson disease, Multiple Sclerosis, etc.).