Natural History Study in Huntington Disease Gene Expansion Carriers (HDGECs) - SHIELD HD (SHIELD HD)

Natural History Study in Prodromal and Manifest Huntington Disease Gene Expansion Carriers (HDGECs) - SHIELD HD

SHIELD HD is an international, multisite, prospective, longitudinal cohort natural history study to assess the natural history of HD and its biomarkers that are associated with modulation of the number of cytosine-adenine-guanine (CAG) repeats in the mutant Huntingtin (HTT) gene.

Approximately 60 patients will be enrolled into the study and followed for up to 24 months at clinical sites in North America and Europe.

The results of this study will inform assessments for a future interventional treatment trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Huntington Disease

Detailed Description

The rationale for this study is to obtain longitudinal information related to Somatic Instability and DNA damage response genes in HDGECs at various stages of the disease. Established assessments of disease progression will also be recorded.

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • North York General Hospital
    • Toronto, Ontario, Canada, M3B 257
      • Centre for Movement Disorders
• France
  • Paris, France, 75013
    • ICM - Institut du Cerveau et de la Moelle épinière
• Germany
  • Muenster, Germany
    • George-Huntington-Institut (GHI)
• United Kingdom
  • London, United Kingdom
    • University College London - Institute of Neurology & The National Hospital for Neurology and Neurosurgery
• United States
  • California
    • San Diego, California, United States, 920161
      • University of California, San Diego (UCSD)
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Washington
    • Spokane, Washington, United States, 99202
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 63 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Huntington disease (HD), genetically confirmed by direct DNA testing, either obtained previously or performed at Screening

Description

Key Inclusion Criteria

Patients who meet all of the following criteria will be eligible to participate in the study:

1. Capacity to comprehend the study objectives and procedures
2. Documentation of genetically confirmed disease by direct DNA testing, defined as a CAG repeat length ≥39 in the HTT gene
3. Ability to undergo and tolerate MRI scans
4. Ability to tolerate blood draws and lumbar punctures

Key Exclusion Criteria

Patients who meet any of the following criteria will be excluded from participation in the study:

1. Any conditions, including severe chorea and dementia, that would prevent either writing or performing pen and paper, tablet, or computer based tasks as determined by the Investigator
2. Treatment with an investigational drug within 30 days prior to screening or within 5 half lives of the investigational drug, whichever is longer
3. History of gene therapy or cell transplantation or any other experimental brain surgery

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DDR gene expression	To assess deoxyribonucleic acid (DNA) damage repair (DDR) gene expression in accessible biofluids and disease trajectories for established and novel biomarkers and clinical outcomes.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare rates of change in biomarkers for disease progression	To compare the rates of change for different outcomes and cytosine adenine guanine (CAG) age product (CAP) Scores.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional biomarkers to be examined	The exploratory objectives of this study are to be determined and may include the examination of additional biomarkers present in CSF, plasma, and whole blood, including but not limited to mutant HTT (mHTT) protein, cytokines, and others, as well as clinical markers of progression.	2 years

Collaborators and Investigators

• Sponsor: CHDI Foundation, Inc.
• Collaborators: Medpace, Inc.
• Investigators: Principal Investigator: Anne Rosser, PhD FRCP, Cardiff University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 19, 2020
• Primary Completion (ANTICIPATED): April 1, 2023
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: May 20, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (ACTUAL): May 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: HD
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: TTX N1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No