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Huntington DiseaseNCT05534139

Clinicopathological MRI and CSF Correlates in Huntington's Disease.

An observational study of Huntington Disease, run by Leiden University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In this study the investigators will link brain iron levels obtained from quantitative susceptibility maps of HD patients with specific and well-known clinical CSF markers for iron accumulation, neurodegeneration and neuroinflammation. Read more about this study

Who is it for?
Ages 21 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Huntington Disease
What is being tested?
7T MRI-scan, CSF collection via lumbar puncture and Blood withdrawal
How many people
90 participants
Where
1 siteNetherlands
Study dates
11 Aug 2021to 31 Aug 2024
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Pre-manifest HD gene carrier: * CAG expansion ≥ 40; * UHDRS Total Motor Score (TMS) ≤ 5; * Total Functional Capacity (TFC) = 13; * Diagnostic Confidence Score < 4. Early-manifest HD gene carrier: * CAG expansion ≥ 36; * Diagnostic Confidence Score = 4; * HD stage I: TFC scores between 11 and 13 inclusive. Moderate manifest HD gene carrier: * CAG expansion ≥ 36; * Diagnostic Confidence Score = 4; * HD stage II: TFC scores between 7 and 10 Control subject: * Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36); * No other known cognitive, neurological or psychiatric disorders.

Who may be able to join

  • Native Dutch/Flemish speaker
  • Ability to undergo MRI scanning;
  • Written informed consent must be obtained from the participant.
  • And in addition:
  • If the participant is a pre-manifest HD gene carrier:
  • CAG expansion ≥ 40;
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  • UHDRS Total Motor Score (TMS) ≤ 5;
  • Total Functional Capacity (TFC) = 13;
  • Diagnostic Confidence Score < 4.
  • If the participant is an early-manifest HD gene carrier:
  • CAG expansion ≥ 36;
  • Diagnostic Confidence Score = 4;
  • HD stage I: TFC scores between 11 and 13 inclusive.
  • If the participant is a moderate manifest HD gene carrier:
  • CAG expansion ≥ 36;
  • Diagnostic Confidence Score = 4;
  • HD stage II: TFC scores between 7 and 11 inclusive.
  • If the participant is a control subject:
  • Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36);
  • No other known cognitive, neurological or psychiatric disorders.

Who cannot join

  • Additional major comorbidities not related to HD (e.g. cardiovascular diseases, coagulopathy, hypertension, diabetes mellitus, and/or other neurological disorders);
  • History of severe head injury;
  • Status of the participant after brain surgery;
  • Past erythrocyte transfusions;
  • Use of investigational drugs or participation in a clinical drug trial within 30 days prior to study visit;
  • Current intoxication, drug or alcohol abuse or dependence;
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  • Pregnancy;
  • Inability to understand the information about the protocol;
  • Severe physical restrictions (completely wheelchair dependent);
  • Severe chorea that, in the investigator's judgment, precludes the patient's participation in and completion of the MRI and/or lumbar puncture.
  • Contra-indication to MRI scanning, such as:
  • Claustrophobia;
  • Pacemakers and defibrillators;
  • Nerve stimulators;
  • Intracranial clips;
  • Intraorbital or intraocular metallic fragments;
  • Cochlear implants;
  • Ferromagnetic implants;
  • Hydrocephalus pump;
  • Intra-utrine device (not all types);
  • Permanent make-up;
  • Tattoos above the shoulders (not all).
  • Contraindications for a lumbar puncture, including:
  • Screening blood test results outside normal ranges(white cell count, neutrophil count, lymphocyte count, hemoglobin, platelets, Prothrombin time (PT), activated partial thromboplastin time (APTT), C-reactive protein (CRP) and serum ferritin) if only marginally decreased or increased this will be decided by the clinical PI;
  • Signs and symptoms of increased intracranial pressure which will be confirmed on the 7T MRI (T1 and FLAIR scan) or by a fundoscopy;
  • Local infections of the skin;
  • Use of anti-coagulant drugs within the last 14 days prior lumbar puncture.

Trial locations and contacts

1 site in 1 country.

Nadine van de Zande, MD contact

071562131

n.a.van_de_zande@lumc.nl

Kasper van der Zwaan, drs contact

k.f.van_der_zwaan@lumc.nl

Netherlands1 site, 1 recruiting

  • Leiden University Medical Centre

    Leiden, South Holland

    Nadine van de Zande, MD

    Kasper van der Zwaan, drs

    Recruiting

Other trials in Netherlands

About this study

Official title: Clinicopathological MRI and CSF Correlates of Iron Accumulation, Neurodegeneration and Neuroinflammation in Huntington's Disease.

In this study the investigators will link brain iron levels obtained from quantitative susceptibility maps of HD patients with specific and well-known clinical CSF markers for iron accumulation, neurodegeneration and neuroinflammation. The relationship between iron accumulation and neuroinflammation, and the clinical and genetic characteristics of HD will be investigated. This will provide an important basis for the evaluation of brain iron levels as an imaging biomarker for disease state in HD and their relationship with the salient pathomechanisms of the disease.

Read the detailed description

This investigator-initiated, single-site cross-sectional study looks at iron accumulation using 7T MR-imaging, CSF and blood. This will be achieved in a two-day visit involving clinical assessments, MRI-scanning of the brain, followed by a lumbar puncture the next day, after overnight fasting. Sixty-five volunteers with HD and 25 volunteers without HD will be included. Of these 65 volunteers with HD, 25 will be premanifest, 20 early manifest and 20 moderate manifest, in order to cover the wide-spectrum of Huntington's Disease.

Being tested
7T MRI-scan, CSF collection via lumbar puncture, Blood withdrawal, Clinical measures
Keywords
Huntington's Disease, Iron accumulation, Quantified susceptibility mapping, QSM, 7T-MRI, CSF, Neurodegeneration, Neuroinflammation
Medical subject headings
Huntington Disease, Nerve Degeneration, Neuroinflammatory Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 7T MRI-scanDiagnostic test

    MRI-scanning of the brain using a 7T-MRI scanner

  • CSF collection via lumbar punctureDiagnostic test

    CSF is collected by doing a lumbar puncture

  • Blood withdrawalDiagnostic test

    Blood is collected by doing a blood withdrawal

  • Clinical measuresDiagnostic test

    UHDRS-Total motor score, UHDRS-short problem behaviour assessment, UHDRS-Cognitive assessments

Study groups in NCT05534139
Study groupRoleWhat they receive
Healthy controlsPartner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36); No other known cognitive, neurological or psychiatric disorders.
Receives: Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures
Premanifest HD expanded gene carrierHDGEC before clinical onset: TMS <5, DCL <4, TFC = 13. No other major comorbidity.
Receives: Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures
Early Manifest HD patientHDGEC after clincial onset: TMS >5, DCL = 4. Early stage of disease: TFC 11-13. No other major comorbidity.
Receives: Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures
Moderate Manifest HD patientHDGEC after clincial onset: TMS >5, DCL = 4. Moderate stage of disease: TFC 7-10. No other major comorbidity.
Receives: Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Quantified Susceptibility Mapping

    MRI analysis to quantify iron accumulation

    Measured: At baseline

  2. Iron in CSF

    Amount of iron and ferritin measured in CSF

    Measured: At baseline

Secondary outcomes (6)

  1. Iron in blood

    Amount of iron and ferritin measured in blood

    Measured: At baseline

  2. Clinical motor signs

    Motor signs obtained using the Unified Huntington's Disease Rating Scale - Total Motor Score. This is a scale assessing motor symptoms of HD, ranging from a score of 0 to 124, where higher scores mean a worse outcome.

    Measured: At baseline

  3. Neuroinflammation and neurodegeneration biomarkers in CSF

    a.o.

    • NFL: pg/mL
    • CHIT1: pg/mL
    • IL-6: pg/mL

    Measured: Baseline

  4. Neuroinflammation and neurodegeneration biomarkers in CSF

    • YKL-40: ng/mL

    Measured: Baseline

  5. Cognitive score

    Assessment of cognitive tests.

    Measured: At baseline

  6. Neuropsychiatric symptoms

    Assessment of short Problem Behaviour Assessment. Each symptom is rated for severity on a 5-point scale : 0 = "not at all"; 1 = trivial; 2 = mild; 3 = moderate (disrupting everyday activities) and 4 = severe or intolerable. Each symptom is also scored for frequency on a 5-point scale as follows: 0 = symptom absent; 1 = less than once weekly; 2 = at least once a week; 3 = most days (up to and including some part of everyday); and 4 = all day, every day. Severity and frequency scores are multiplied to produce an overall 'PBA score' for each symptom.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2022
  2. Study start11 Aug 2021
  3. Primary completion31 Aug 2023 (estimated)
  4. Study completion31 Aug 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05534139
Sponsor's protocol ID
P19.030
Status last verified
Sep 2022
First submitted
15 Aug 2022
Last updated
9 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

An observational study of Huntington Disease, run by Leiden University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Nadine van de Zande, MD (071562131, n.a.van_de_zande@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quantified Susceptibility Mapping (time frame: At baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05534139.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2022.

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