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Study to Measure Cerebrospinal Fluid Mutant Huntingtin Protein in Participants With Early Manifest Stage I or Stage II Huntington's Disease

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ClinicalTrials.gov Identifier: NCT03664804
Recruitment Status : Active, not recruiting
First Posted : September 11, 2018
Last Update Posted : August 5, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
The study is designed as a multi-site, prospective, 15-month longitudinal, cohort study measuring CSF mHTT in participants with early manifest Stage I or Stage II Huntington's disease (HD).

Condition or disease Intervention/treatment Phase
Huntington's Disease Other: No Study Drug was Administered in this Study Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Multi-Site, Prospective, Longitudinal, Cohort Study Measuring Cerebrospinal Fluid-Mutant Huntingtin Protein in Patients With Huntington's Disease
Actual Study Start Date : December 5, 2018
Estimated Primary Completion Date : September 18, 2020
Estimated Study Completion Date : September 18, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Participants with Early Manifest Stage I or II HD
No study drug was administered in this study
Other: No Study Drug was Administered in this Study
No study drug was administered in this study




Primary Outcome Measures :
  1. Change from Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test, and IS [ Time Frame: Baseline to 15 Months ]
    cUHDRS = composite Unified Huntington's Disease Rating Scale TFC = Total Functional Capacity Scale TMS = Total Motor Scale SDMT = Symbol Digit Modalities Test SWR = Stroop Word Reading IS = Independence Scale

  2. Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
    CSF = Cerebrospinal Fluid NfL = Neurofilament Light Chain

  3. Change from Baseline in Brain Atrophy Endpoints (e.g., Whole Brain Volume Decline, Caudate Volume Decline) as Determined by Brain MRI, at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]

Secondary Outcome Measures :
  1. Within-Participant Change from Baseline in CSF mHTT Levels at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
    mHTT=Mutant Huntingtin Protein

  2. Association of Change from Baseline in Clinical Measures (cUHDRS, TFC, TMS, SDMT, SWR, and IS) at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
  3. Association of Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
  4. Association of Change from Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Capacity to consent to participate in the study as assessed using the Evaluation to Sign Consent tool and investigator judgment
  • Age 25 to 65 years, inclusive, at the time of signing Informed Consent Form
  • Early manifest, Stage I or Stage II HD (defined as TFC of 7-13, inclusive)
  • Genetically confirmed disease (CAG repeat length ≥ 36 in huntingtin gene by direct DNA testing)
  • Body mass index ≥18 and ≤32 kg/m2; total body weight >50 kg
  • Ability to undergo and tolerate MRI scans
  • Ability to tolerate blood draws and lumbar puncture
  • Ability and willingness to comply with all aspects of the protocol, including completion of interviews and questionnaires and carrying/wearing of a digital monitoring device
  • Stable medical, psychiatric, and neurological status for at least 12 weeks prior to screening and at the time of enrollment
  • Signed study companion consent for participation, if a study companion is available
  • For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the observational period

Exclusion Criteria:

  • Any condition, including severe chorea, that would prevent either writing or performing pen and paper or smartphone-based tasks
  • History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening
  • Current active psychosis, confusional state, or violent behavior
  • Any serious medical condition or clinically significant laboratory, vital sign, or electrocardiogram abnormalities at screening that, in the investigator's judgement, precludes the participant's safe participation in and completion of the study
  • Pregnant or breastfeeding, or intending to become pregnant during the study
  • Positive for hepatitis C virus antibody or hepatitis B surface antigen at screening
  • Known HIV infection
  • Current or previous use of an antisense oligonucleotide (including small interfering RNA)
  • Current use of antipsychotics prescribed for psychosis, cholinesterase inhibitors, memantine, amantadine, or riluzole including use within 12 weeks of enrollment
  • Treatment with an investigational drug within 30 days prior to screening or 5 half-lives of the investigational drug, whichever is longer
  • Antiplatelet or anticoagulant therapy within the 14 days prior to screening or anticipated use during the study, including, but not limited, to aspirin (unless ≤81mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban
  • History of bleeding diathesis or coagulopathy; platelet count < lower limit of normal unless stable and assessed by the Investigator and Sponsor Medical Monitor to be not clinically significant
  • Malignancy within 5 years prior to screening, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
  • History of gene therapy or cell transplantation or any other experimental brain surgery
  • Concurrent or planned concurrent participation in any clinical study without approval of the Medical Monitor
  • Presence of implanted shunt for the drainage of CSF or an implanted CNS catheter
  • Pre-existing structural brain lesion as assessed by MRI scan

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664804


Locations
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United States, California
University of California Davis Medical System
Sacramento, California, United States, 95817
United States, Colorado
Rocky Mountain Movement Disorders Center
Englewood, Colorado, United States, 80113
United States, District of Columbia
Georgetown University; Research Division, Psychiatry
Washington, District of Columbia, United States, 20007
United States, Kansas
Hereditary Neurological Disease Centre (HNDC)
Wichita, Kansas, United States, 67226
United States, Maryland
John Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Texas
The University of Texas Health Science Center at Houston; McGovern Medical School
Houston, Texas, United States, 77030
Canada, British Columbia
The University of British Columbia; The Centre for Huntington Disease
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
Centre for Movement Disorders (Neuropharm Consulting Inc.)
Markham, Ontario, Canada, L6B 1C9
Germany
Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
Berlin, Germany, 10117
St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum
Bochum, Germany, 44791
Universitätsklinikum Ulm; Klinik für Neurologie
Ulm, Germany, 89081
United Kingdom
NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
Birmingham, United Kingdom, B15 2FG
Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
Cardiff, United Kingdom, CF24 4HQ
National Hospital For Neurology and Neurosurgery
London, United Kingdom, WC1N 3BG
Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03664804     History of Changes
Other Study ID Numbers: BN40422
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: August 5, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders