Enroll -HD: A Prospective Registry Study in a Global Huntington's Disease Cohort

• ClinicalTrials.gov Identifier: NCT01574053
• Recruitment Status: Recruiting
• First Posted: April 10, 2012
• Last Update Posted: February 28, 2024
• Sponsor: CHDI Foundation, Inc.
• Information provided by (Responsible Party): CHDI Foundation, Inc.

Tracking Information

• First Submitted Date: April 6, 2012
• First Posted Date: April 10, 2012
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: July 2012
• Estimated Primary Completion Date: January 2062 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2024)

• Motor Assessments: Unified Huntington's Disease Rating Scale (UHDRS) 99 Motor, UHDRS '99 Diagnostic Confidence Level [ Time Frame: through study completion, an average of 1 year ]
  The motor section of the UHDRS assesses motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. UHDRS 99 Motor, UHDRS Diagnostic Confidence Level.
• Functional Assessments: UHDRS '99 Total Functional Capacity, UHDRS '99 Functional Assessment Scale, UHDRS '99 Independence Scale [ Time Frame: through study completion, an average of 1 year ]
  The Total Functional Capacity, Functional Assessment and Independence Subscales of the UHDRS '99 will be used to assess participants' functional status. The Total Functional Capacity scale has established psychometric properties including inter-rater reliability and validity, based on radiographic measures of disease progression.
• Problem Behaviors Assessment-Short (PBA-s) [ Time Frame: through study completion, an average of 1 year ]
  The Problem Behavioral Assessment Short Version (PBA-s) will be used to perform behavioral assessments. This instrument measures frequency and severity of symptoms related to altered affect, thought content and coping styles.
• Cognitive Assessments: Symbol Digit Modality Test; Stroop Color Naming; Stroop Word Reading; Categorical Verbal Fluency [ Time Frame: through study completion, an average of 1 year ]
  Cognition will be assessed using the Categorical Verbal Fluency Test, Symbol Digit Modality Test and Stroop Color and Word Reading Test. Verbal fluency is a commonly used neuropsychological test which examines the ability to spontaneously produce words orally within a fixed time span. For category fluency, words must be produced according to semantic constraints. The measure of performance used will be the number of correctly generated words within 60 seconds.

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Enroll -HD: A Prospective Registry Study in a Global Huntington's Disease Cohort
• Official Title: Enroll -HD: A Prospective Registry Study in a Global Huntington's Disease Cohort
• Brief Summary: Enroll-HD is a longitudinal, observational, multinational study that integrates two former Huntington's disease (HD) registries-REGISTRY in Europe, and COHORT in North America and Australasia-while also expanding to include sites in Latin America. More than 30,000 participants have now enrolled into the study. With annual assessments and no end date, Enroll-HD has built a large and rich database of longitudinal clinical data and biospecimens that form the basis for studies developing tools and biomarkers for progression and prognosis, identifying clinically-relevant phenotypic characteristics, and establishing clearly defined endpoints for interventional studies. Periodic cuts of the database are now available to any interested researcher to use in their research - visit www.enroll-hd.org/for-researchers/access-data/ to learn more.
• Detailed Description: The primary objective of Enroll-HD is to develop a comprehensive repository of prospective and systematically collected clinical research data (demography, clinical features, family history, genetic characteristics) and biological specimens (blood) from individuals with manifest HD, unaffected individuals known to carry the HD mutation or at risk of carrying the HD mutation, and control research participants (e.g., spouses, siblings or offspring of HD mutation carriers known not to carry the HD mutation). Enroll-HD is conceived as a broad-based and long-term project to maximize the efficiencies of non-clinical research and participation in clinical research. With more than 150 active clinical sites in 23 countries, Enroll-HD is now the largest HD database available and is accessible to any interested researcher - visit www.enroll-hd.org/for-researchers/access-data/ to learn more.
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: 1 Year

Biospecimen

Retention:   Samples With DNA

Description:

Blood

• Sampling Method: Non-Probability Sample
• Study Population: Patients with HD and their family members are recruited from specialty clinics (Human Genetics, Neurology, Psychiatry) that advise and treat people affected by HD. In addition, in some areas community clinics and neurologists who see HD patients recruit participants for this study. Participants also receive information about the study through websites, clinical practices, support groups, advocacy newsletters, etc. and place a direct request to be considered for participation in the study. Community controls are identified by study site staff (using advertisements, flyers and newsletters) with the support of the Enroll-HD operational staff.
• Condition: Huntington's Disease
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Landwehrmeyer GB, Fitzer-Attas CJ, Giuliano JD, Goncalves N, Anderson KE, Cardoso F, Ferreira JJ, Mestre TA, Stout JC, Sampaio C. Data Analytics from Enroll-HD, a Global Clinical Research Platform for Huntington's Disease. Mov Disord Clin Pract. 2016 Jun 22;4(2):212-224. doi: 10.1002/mdc3.12388. eCollection 2017 Mar-Apr.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 9, 2024): 35000
• Original Estimated Enrollment (submitted: April 9, 2012): 15000
• Estimated Study Completion Date: January 2062
• Estimated Primary Completion Date: January 2062 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Carriers: This group comprises the primary study population and consists of individuals who carry the HD gene expansion mutation.
• Controls: This group comprises the comparator study population and consists of individuals who do not carry the HD expansion mutation.

These two major categories can be further subdivided into six different subgroups of eligible individuals:

• Manifest/Motor-manifest HD: Carriers with clinical features that are regarded in the opinion of the investigator as diagnostic of HD.
• Pre-Manifest/-Motor-manifest HD: Carriers without clinical features regarded as diagnostic of HD.
• Genotype Unknown: This group includes a first or second degree relative (i.e., related by blood to a carrier) who has not undergone predictive testing for HD and therefore has an undetermined carrier status.
• Genotype Negative: This group includes a first or second degree relative (i.e., related by blood to a carrier) who has undergone predictive testing for HD and is known not to carry the HD expansion mutation.
• Family Control: Family members or individuals not related by blood to carriers (e.g., spouses, partners, caregivers).
• Community Controls: Individuals unrelated to HD carriers who did not grow up in a family affected by HD. Data collected from community controls will be used for generation of normative data for sub-studies.

Participant status will be captured in the study database using 2 variables: 1) Investigator Determined Status: this will be based on clinical signs and symptoms and genotyping performed as part of medical care, and will be updated at every visit; and 2) Research Genotyping Status: this will be based on genotyping conducted as part of Enroll-HD study procedures. Based on research genotyping, participants will be reclassified under this variable from Genotype Unknown to 'Carriers' or 'Controls'. Investigators and participants will be blinded to this reclassification.

Exclusion Criteria:

• Individuals who do not meet inclusion criteria,
• Individuals with choreic movement disorders in the context of a negative test for the HD gene mutation.
• For Community Controls: those individuals with a major central nervous system disorder will be excluded (e.g. stroke, Parkinson's disease, multiple sclerosis, etc.).

Participants under 18 may be eligible to participate (if they have juvenile-onset HD).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Noopur Modi; Info@Enroll-HD.org

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Canada, Chile, Colombia, Denmark, France, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, Portugal, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT01574053
• Other Study ID Numbers: Enroll -HD
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: CHDI Foundation, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CHDI Foundation, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bernhard G Landwehrmeyer, MD, PhD; University of Ulm
• Study Director: Jamie Levey; CHDI Foundation, Inc.

• PRS Account: CHDI Foundation, Inc.
• Verification Date: February 2024