Clinicopathological MRI and CSF Correlates in Huntington's Disease.

NCT ID: NCT05534139

Last Updated: 2022-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-08-11

Study Completion Date

2024-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Huntington Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Healthy controls

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.

7T MRI-scan

Intervention Type DIAGNOSTIC_TEST

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

CSF collection via lumbar puncture

Intervention Type DIAGNOSTIC_TEST

CSF is collected by doing a lumbar puncture

Blood withdrawal

Intervention Type DIAGNOSTIC_TEST

Blood is collected by doing a blood withdrawal

Clinical measures

Intervention Type DIAGNOSTIC_TEST

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

Premanifest HD expanded gene carrier

HDGEC before clinical onset: TMS \<5, DCL \<4, TFC = 13. No other major comorbidity.

7T MRI-scan

Intervention Type DIAGNOSTIC_TEST

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

CSF collection via lumbar puncture

Intervention Type DIAGNOSTIC_TEST

CSF is collected by doing a lumbar puncture

Blood withdrawal

Intervention Type DIAGNOSTIC_TEST

Blood is collected by doing a blood withdrawal

Clinical measures

Intervention Type DIAGNOSTIC_TEST

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

Early Manifest HD patient

HDGEC after clincial onset: TMS \>5, DCL = 4. Early stage of disease: TFC 11-13. No other major comorbidity.

7T MRI-scan

Intervention Type DIAGNOSTIC_TEST

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

CSF collection via lumbar puncture

Intervention Type DIAGNOSTIC_TEST

CSF is collected by doing a lumbar puncture

Blood withdrawal

Intervention Type DIAGNOSTIC_TEST

Blood is collected by doing a blood withdrawal

Clinical measures

Intervention Type DIAGNOSTIC_TEST

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

Moderate Manifest HD patient

HDGEC after clincial onset: TMS \>5, DCL = 4. Moderate stage of disease: TFC 7-10. No other major comorbidity.

7T MRI-scan

Intervention Type DIAGNOSTIC_TEST

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

CSF collection via lumbar puncture

Intervention Type DIAGNOSTIC_TEST

CSF is collected by doing a lumbar puncture

Blood withdrawal

Intervention Type DIAGNOSTIC_TEST

Blood is collected by doing a blood withdrawal

Clinical measures

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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7T MRI-scan

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

Intervention Type DIAGNOSTIC_TEST

CSF collection via lumbar puncture

CSF is collected by doing a lumbar puncture

Intervention Type DIAGNOSTIC_TEST

Blood withdrawal

Blood is collected by doing a blood withdrawal

Intervention Type DIAGNOSTIC_TEST

Clinical measures

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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;
* 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.

Exclusion Criteria

* 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;
* 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.
Minimum Eligible Age

21 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Brighton & Sussex Medical School

OTHER

Sponsor Role collaborator

University of Ulm

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Susanne T de Bot, MD, PhD

MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Susanne de Bot, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Neurology

Locations

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Leiden University Medical Centre

Leiden, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Nadine van de Zande, MD

Role: CONTACT

071562131

Kasper van der Zwaan, drs

Role: CONTACT

Facility Contacts

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Nadine van de Zande, MD

Role: primary

Kasper van der Zwaan, drs

Role: backup

Other Identifiers

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P19.030

Identifier Type: -

Identifier Source: org_study_id

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