Data Analytics from Enroll‐HD, a Global Clinical Research Platform for Huntington's Disease

Abstract

Background: The study of complex neurodegenerative diseases is moving away from hypothesisdriven biological methods toward large scale multimodal approaches, requiring standardized collaborative efforts. Enroll-HD exemplifies such an integrated clinical research platform, designed and implemented to meet the research and clinical needs of Huntington's disease (HD). The aim of this study was to describe the unique organization of Enroll-HD and report baseline data analyses of its core study. Methods: The Enroll-HD platform incorporates electronic data capture, biosampling, and a longitudinal observational study spanning four continents (ClinicalTrials.gov Identifier: NCT01574053). The primary study population includes HD gene expansion carriers (HDGECs; CAG expansion ≥36), subdivided into manifest/ premanifest HD. The control population consists of genotype-negative first-degree relatives and family controls not genetically related. The study includes 10 core clinical assessments covering motor, cognitive, and behavioral domains. Results: This data set comprises 1,534 participants (HDGEC = 1,071; controls = 463). Participant retention was high; 42 participants prematurely withdrew from the study. Mean AE standard deviation SD CAG repeat size was 43.5 AE 3.5 for HDGECs and 19.8 AE 3.4 for controls. Motor and behavioral assessments identified numerical differences between controls and HDGECs (manifest > premanifest > controls). Functional and independence assessments were generally similar for the premanifest and control groups with overlap in range of scores obtained. For the majority of cognitive tests, there were large differences between participants with manifest HD and all other groups. Conclusions: These first data from the Enroll-HD clinical research platform demonstrate the maturity and potential of the platform in collecting high-quality, clinically relevant data. Future data sets will be substantially larger as the platform expands longitudinally and regionally.

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

“…Nevertheless, the progression measures show the expected relationship with change in TMS and TFC in both TRACK-HD and REGISTRY indicating their clinical relevance. However, future development of the progression statistic and confirmation of the genetic association in subjects from ongoing large studies such as ENROLL (27), with data collected more systematically than in REGISTRY but in less detail than TRACK-HD, would be ideal.…”

Statin use and delayed onset of Huntington's disease

“…In addition to manifest HD patients, the database includes individuals with premotor HD, genotype‐negative individuals, and family control participants without HD. Enroll‐HD annually collects information on all research participants regarding current and past medications, and data are scrutinized for quality and accuracy using a risk‐based monitoring approach …”

Validation of a prognostic index for Huntington's disease

“…Resources for trial recruitment include clinical research platforms, such as Enroll‐HD . Enroll‐HD has an embedded observational study with regular visits at which clinical data are collected.…”