A novel, hybrid, single- and multi-site clinical trial design for CLN3 disease, an ultra-rare lysosomal storage disorder

Clin Trials. 2019 Oct;16(5):555-560. doi: 10.1177/1740774519855715. Epub 2019 Jun 11.


Background: Travel burden often substantially limits the ability of individuals to participate in clinical trials. Wide geographic dispersion of individuals with rare diseases poses an additional key challenge in the conduct of clinical trials for rare diseases. Novel technologies and methods can improve access to research by connecting participants in their homes and local communities to a distant research site. For clinical trials, however, understanding of factors important for transition from traditional multi-center trial models to local participation models is limited. We sought to test a novel, hybrid, single- and multi-site clinical trial design in the context of a trial for Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 disease), a very rare pediatric neurodegenerative disorder.

Methods: We created a "hub and spoke" model for implementing a 22-week crossover clinical trial of mycophenolate compared with placebo, with two 8-week study arms. A single central site, the "hub," conducted screening, consent, drug dispensing, and tolerability and efficacy assessments. Each participant identified a clinician to serve as a collaborating "spoke" site to perform local safety monitoring. Study participants traveled to the hub at the beginning and end of each study arm, and to their individual spoke site in the intervening weeks.

Results: A total of 18 spoke sites were established for 19 enrolled study participants. One potential participant was unable to identify a collaborating local site and was thus unable to participate. Study start-up required a median 6.7 months (interquartile range = 4.6-9.2 months). Only 33.3% (n = 6 of 18) of spoke site investigators had prior clinical trial experience, thus close collaboration with respect to study startup, training, and oversight was an important requirement. All but one participant completed all study visits; no study visits were missed due to travel requirements.

Conclusions: This study represents a step toward local trial participation for patients with rare diseases. Even in the context of close oversight, local participation models may be best suited for studies of compounds with well-understood side-effect profiles, for those with straightforward modes of administration, or for studies requiring extended follow-up periods.

Trial registration: ClinicalTrials.gov NCT01399047.

Keywords: Rare disease; central institutional review board; neuronal ceroid lipofuscinosis; trial design; trial infrastructure; trial innovation; trial networks.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Clinical Trials as Topic / organization & administration*
  • Cross-Over Studies
  • Ethics Committees, Research / organization & administration
  • Health Services Accessibility / organization & administration*
  • Humans
  • Multicenter Studies as Topic*
  • Neuronal Ceroid-Lipofuscinoses / therapy
  • Rare Diseases / therapy

Associated data

  • ClinicalTrials.gov/NCT01399047