Safety and feasibility of research lumbar puncture in Huntington’s disease: the HDClarity cohort and bioresource

Abstract

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington's disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objectives: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity (NCT02855476) is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e. CSF was collected), amounting to 10,610mL of CSF and 8,200mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusions: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now established as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.

Lumbar puncture safety and tolerability in premanifest and manifest Huntington’s disease: a multi-analysis cross-sectional study

“…The HDClarity study (NCT02855476) 5 is an ongoing, international, multi-site, longitudinal CSF collection initiative aiming to recruit 1200 participants. The primary objective is to collect high-quality CSF samples for the evaluation of biomarkers and pathways that will enable the development of novel treatments for HD.…”

“…A recent study by Rodrigues et al 5 addressed for the first time the safety profile of LP in a cohort of patients with Huntington's disease and controls who took part in the largest CSF collection initiative, HDClarity. They found that the adverse events rate in their cohort was similar to that reported in other neurological diseases or the general population and that age, gender, BMI, and disease burden score (DBS), as a surrogate of disease status, did not show association with the rate of post LP headache.…”

Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities

“…CSF huntingtin quantification remains limited by the sensitivity of current mHTT assays -many far from clinical motor onset individuals have unquantifiably low levels 11,99 , making therapeutic lowering difficult to assess; and the difficulty of quantifying wtHTT either independently or through inference from the total HTT level based on current assays 100 . More broadly, the HD biomarker field lacks well-powered replication studies, but the HDClarity bioresource has a large and expanding CSF and plasma collection for this purpose 101 .…”