Biomarker Profiling in Individuals at Risk for Prion Disease

We are doing this research to identify biomarkers in individuals who are at-risk for familial prion disease. We hope to use these biomarkers to predict timing of disease onset in pre-symptomatic individuals and to guide the direction of future clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Prion Diseases; Familial Fatal Insomnia; CJD (Creutzfeldt Jakob Disease); GSS; FFI

Detailed Description

This study aims to measure biomarkers longitudinally in individuals at risk of developing genetic prion disease to identify clinical assays and molecular markers that: can inform our understanding of pre-clinical pathology, predict timing of disease onset in pre-symptomatic individuals, and enable development and evaluation of novel treatment efficacy in pre-symptomatic or early symptomatic individuals.

Participation in the study involves annual visits to the clinic site in Charlestown, MA. Study visits include: a medical exam, blood draws, cognitive tests and questionnaires, spinal fluid collection, and (optional) MRI.

Travel support and stipend is provided for interested individuals.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Sophia D'Alessandro; Phone Number: 617-726-4026; Email: sedalessandro@mgh.harvard.edu
• Study Contact Backup: Name: Alison McManus, DNP; Email: ajmcmanus@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Recruiting
      • Alzheimer's Clinical and Translational Research Unit
      • Principal Investigator: Steven E Arnold, MD
      • Contact: Sophia D'Alessandro; Phone Number: 617-726-4026; Email: sedalessandro@mgh.harvard.edu
      • Contact: Alison McManus, DNP; Phone Number: 6176434848; Email: AJMCMANUS@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

100 people ages 18-85 with history of genetic prion disease and 50 non-carrier healthy controls

Description

Inclusion Criteria:

1. 1. Aged 18 - 85,

2. One of the following:

   1. Known carrier of pathogenic PRNP mutation
   2. History of probable or definite prion disease in biological parent and other family members
   3. Non-carrier family members and/or unrelated previously enrolled negative control volunteers
3. Medically safe to undergo blood draw, lumbar puncture and cognitive testing,
4. Adequate visual and auditory acuity to complete cognitive testing,
5. Fluent in English,
6. At least 5 years of education,
7. Capable of providing informed consent and following study procedures,
8. No contraindications to MRI scanning as determined via the Martinos Center MRI Screening process (for PRNP mutation carriers ONLY)

Exclusion Criteria:

1. Any CNS disease other than asymptomatic or early prion disease, such as clinical stroke, brain tumor, multiple sclerosis, significant head trauma with persistent neurological or neurocognitive deficits, Alzheimer's disease, Parkinson's disease, frontotemporal lobar degeneration or other known neurodegenerative disease,
2. History of alcohol or other substance abuse or dependence within the past two years,
3. Any significant systemic illness or unstable medical condition or pregnancy that could represent safety risk or affect participation in the study,
4. Coagulopathy or anti-coagulant therapy (such as Coumadin) increasing the risk for phlebotomy or lumbar puncture resulting in PT/PTT and INR within 1.5 standard deviation over the upper normal limit.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Individuals with a family history of Prion disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF YKL40	Levels of YKL40	1 year
CSF Tau	Levels of Tau	1 year
CSF Nfl	Levels of Nfl	1 year
CSF GFAP	Levels of GFAP	1 year
CSF Prion protein	Levels of Prion protein	1 year
CSF Prion biomarkers	RT-QuIC levels	1 year
Cognition	NIH Toolbox measures of cognition	1 year

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Broad Institute of MIT and Harvard
• Investigators: Principal Investigator: Steven E Arnold, MD, MGH

Publications and helpful links

General Publications

• Vallabh SM, Mortberg MA, Allen SW, Kupferschmid AC, Kivisakk P, Hammerschlag BL, Bolling A, Trombetta BA, Devitte-McKee K, Ford AM, Sather LE, Duffy G, Rivera A, Gerber J, McManus AJ, Minikel EV, Arnold SE. Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion. Neurology. 2024 Jul 23;103(2):e209506. doi: 10.1212/WNL.0000000000209506. Epub 2024 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Neurodegenerative Diseases; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Central Nervous System Infections; Sleep Initiation and Maintenance Disorders; Insomnia, Fatal Familial; Prion Diseases
• Other Study ID Numbers: 2017P000214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No