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HDClarity: a Multi-site Cerebrospinal Fluid Collection Initiative to Facilitate Therapeutic Development for Huntington's Disease (HDClarity)

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ClinicalTrials.gov Identifier: NCT02855476
Recruitment Status : Recruiting
First Posted : August 4, 2016
Last Update Posted : August 15, 2019
Sponsor:
Collaborator:
CHDI Foundation, Inc.
Information provided by (Responsible Party):
Edward Wild, University College, London

Tracking Information
First Submitted Date July 26, 2016
First Posted Date August 4, 2016
Last Update Posted Date August 15, 2019
Actual Study Start Date January 2017
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 3, 2016)
Number of CSF samples banked [ Time Frame: Up to 3 years ]
The primary aim of HDClarity is the generation of a CSF sample repository to facilitate therapeutic development for HD.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02855476 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: August 3, 2016)
  • Huntingtin protein level in cerebrospinal fluid [ Time Frame: Up to 3 years ]
    The concentration of mutant and total huntingtin level in CSF will be quantified and its relationship to disease severity assessed
  • Kynurenine metabolites in cerebrospinal fluid [ Time Frame: Up to 3 years ]
    The concentration of metabolites of the kynurenine pathway in CSF will be quantified and their relationship to disease severity assessed
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title HDClarity: a Multi-site Cerebrospinal Fluid Collection Initiative to Facilitate Therapeutic Development for Huntington's Disease
Official Title HDClarity: a Multi-site Cerebrospinal Fluid Collection Initiative to Facilitate Therapeutic Development for Huntington's Disease
Brief Summary HDClarity will seek at least 1200 research participants at different stages of Huntington's disease (HD). The primary objective is to collect a high quality CSF sample for evaluation of biomarkers and pathways that will enable the development of novel treatments for HD. The secondary objective is to generate a high quality plasma sample collection matching the CSF collections, which will also be used to evaluate biomarkers and pathways of relevance to HD research and development.
Detailed Description

All participants will attend a screening and sampling visit. During the screening visit, medical history, and clinical and phenotypic data will be obtained. Participants who meet the eligibility requirements are willing to continue in the study, will return for a sampling visit during which ≤20ml CSF and approximately 50ml blood will be collected following an overnight fast: blood will be obtained via venipuncture and CSF will be obtained via lumbar puncture using local anaesthetic if required. Some participants may be invited to return for an Optional Repeat Sampling Visit approximately 4-8 weeks later.

When participants have completed the Initial Sampling Visit, and Optional Repeat Sampling Visit, if relevant, their participation in HDClarity will be considered completed. However, participants may be invited to participate in the study multiple times, allowing at least 11 months between Screening Visits.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
CSF, serum, plasma (participant DNA available via Enroll-HD)
Sampling Method Non-Probability Sample
Study Population A minimum of 1200 male and female participants, aged between 21 and 75 years, inclusive, will be enrolled in the study. Eligible participants include healthy controls, people who are in the early pre-manifest and late pre-manifest stage of HD, and people diagnosed with early HD, moderate HD or advanced HD.
Condition Huntington's Disease
Intervention Not Provided
Study Groups/Cohorts
  • Early Pre-manifest HD
    Huntington's disease gene expansion carriers who not have clinical diagnostic motor features of HD
  • Late Pre-manifest HD
    Huntington's disease gene expansion carriers who not have clinical diagnostic motor features of HD, but who have a higher burden of disease compared to the Early Pre-manifest HD cohort
  • Early Manifest HD
    Huntington's disease gene expansion carriers who have clinical diagnostic motor features of HD defined as Stage I or Stage II HD
  • Moderate Manifest HD
    Huntington's disease gene expansion carriers who have clinical diagnostic motor features of HD defined as Stage III HD
  • Late Manifest HD
    Huntington's disease gene expansion carriers who have clinical diagnostic motor features of HD defined as Stage IV-V HD
  • Controls
    Have no known family history of HD; or have known family history of HD but have been tested for the huntingtin gene glutamine codon (CAG) expansion and are not at genetic risk for HD.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 16, 2019)
1200
Original Estimated Enrollment
 (submitted: August 3, 2016)
600
Estimated Study Completion Date April 1, 2021
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. All eligible participants:

    a. Are 21-75 years of age, inclusive; and b. Are capable of providing informed consent or have a legal representative authorized to give consent on behalf of the participant; and c. Are capable of complying with study procedures, including fasting, blood sampling and lumbar puncture; and d. Are participating in the Enroll-HD study; and e. Will have had an Enroll-HD visit within two months of the Screening Visit.

  2. For the Healthy Control group, participants eligible are persons who meet the following criteria:

    a. Have no known family history of HD; or b. Have known family history of HD but have been tested for the huntingtin gene CAG expansion and are not at genetic risk for HD (CAG < 36).

  3. For the Early Pre-manifest HD group, participants eligible are persons who meet the following criteria:

    a. Do not have clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4; and b. Have CAG expansion ≥ 40; and c. Have burden of pathology score, computed as (CAG - 35.5) × age, < 250.

  4. For the Late Pre-manifest HD group, participants eligible are persons who meet the following criteria:

    1. Do not have clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4; and
    2. Have CAG expansion ≥ 40; and
    3. Have burden of pathology score, computed as (CAG - 35.5) x age, ≥ 250.
  5. For Early Manifest HD group, participants eligible are persons who meet the following criteria:

    1. Have clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4; and
    2. Have CAG expansion ≥ 40; and
    3. Have Stage I or Stage II HD, defined as UHDRS Total Functional Capacity (TFC) scores between 7 and 13 inclusive.
  6. For Moderate Manifest HD group, participants eligible are persons who meet the following criteria:

    1. Have clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4; and
    2. Have CAG expansion ≥ 40; and
    3. Have Stage III HD, defined as UHDRS TFC scores between 3 and 6, inclusive.
  7. For Advanced Manifest HD group, participants eligible are persons who meet the following criteria:

    1. Have clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4; and
    2. Have CAG expansion ≥ 40; and
    3. Have Stage IV HD, defined as UHDRS TFC scores between 0 and 2, inclusive.

Exclusion Criteria:

1. For all groups, participants are ineligible if they meet any of the following exclusion criteria:

  1. Use of investigational drugs or participation in a clinical drug trial within 30 days prior to Sampling Visit; or
  2. Current intoxication, drug or alcohol abuse or dependence; or
  3. If using any medications or nutraceuticals, the use of inappropriate (e.g., non prescribed) or unstable dose within 30 days prior to Sampling Visit; or
  4. Significant medical, neurological or psychiatric co-morbidity likely, in the judgment of the Site Principal Investigator, to impair participant's ability to complete study procedures, or likely to reduce the utility of the samples and data for the study of HD; or
  5. Needle phobia, frequent headache, significant lower spinal deformity or major surgery; or
  6. Antiplatelet or anticoagulant therapy within the 14 days prior to Sampling Visit, including but not limited to: aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban; or
  7. Clotting or bruising disorder; or
  8. Screening blood test results more than 10% outside the lab's normal range for the following: white cell count, neutrophil count, lymphocyte count, hemoglobin (Hb), platelets, prothrombin time (PT) and activated partial thromboplastin time (APTT), or any combination of blood test results that the Site Principal Investigator deems to be of clinical significance; or
  9. Screening blood test results for C-reactive protein (CRP)>2× upper limit of normal; or
  10. Predictable non-compliance as assessed by Site Principal Investigator; or
  11. Inability or unwillingness to undertake any of the study procedures; or
  12. Exclusion during history or physical examination, final decision to be made by the Site Principal Investigator; including but not limited to:

i. any reason to suspect abnormal bleeding tendency, e.g. easy bruising, petechial rash; or ii. any reason to suspect new focal neurological lesion, e.g. new headache, optic disc swelling, asymmetric focal long tract signs; or iii. any other reason that, in the clinical judgment of the Site Principal Investigator, it is felt that lumbar puncture performed per this protocol and associated manuals is unsafe without brain imaging.

m. Serious Adverse Event (SAE) related to study procedures during or following any previous HDClarity Sampling Visit (if applicable), or SAE related to any other lumbar puncture in the previous 12 months.

Sex/Gender
Sexes Eligible for Study: All
Ages 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Stefanie Gosling, BSc +44 203 108 7482 hdclarity-cc@enroll-hd.org
Contact: Gail Owen, PhD +44 1273 640 688 g.owen@ucl.ac.uk
Listed Location Countries Canada,   Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02855476
Other Study ID Numbers 15/0519
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: The cerebrospinal fluid (CSF) and plasma samples collected in this study will be the basis of future biomarker analysis studies. A Scientific Advisory Committee which will decide how the samples will be analysed.
Responsible Party Edward Wild, University College, London
Study Sponsor University College, London
Collaborators CHDI Foundation, Inc.
Investigators
Principal Investigator: Edward J Wild, MA, MB BChir, MRCP, PhD University College, London
PRS Account University College, London
Verification Date April 2019