Clinicopathological MRI and CSF Correlates in Huntington's Disease.

NCT05534139 | Unknown

• 1 other identifier: P19.030
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Huntington Disease

Keywords

Huntington's Disease; Iron accumulation; Quantified susceptibility mapping; QSM; 7T-MRI; CSF; Neurodegeneration; Neuroinflammation

Outcome Measures

Primary Outcomes (2)

• Quantified Susceptibility Mapping

  MRI analysis to quantify iron accumulation

  At baseline

• Iron in CSF

  Amount of iron and ferritin measured in CSF

  At baseline

Secondary Outcomes (6)

• Iron in blood

  At baseline

• Clinical motor signs

  At baseline

• Neuroinflammation and neurodegeneration biomarkers in CSF

  Baseline

• Neuroinflammation and neurodegeneration biomarkers in CSF

  Baseline

• Cognitive score

  At baseline

Study Arms (4)

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.

Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures

Premanifest HD expanded gene carrier

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

Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures

Early Manifest HD patient

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

Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures

Moderate Manifest HD patient

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

Diagnostic Test: 7T MRI-scan; Diagnostic Test: CSF collection via lumbar puncture; Diagnostic Test: Blood withdrawal; Diagnostic Test: Clinical measures

Interventions

7T MRI-scan DIAGNOSTIC_TEST

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

Early Manifest HD patient; Healthy controls; Moderate Manifest HD patient; Premanifest HD expanded gene carrier

CSF collection via lumbar puncture DIAGNOSTIC_TEST

CSF is collected by doing a lumbar puncture

Early Manifest HD patient; Healthy controls; Moderate Manifest HD patient; Premanifest HD expanded gene carrier

Blood withdrawal DIAGNOSTIC_TEST

Blood is collected by doing a blood withdrawal

Early Manifest HD patient; Healthy controls; Moderate Manifest HD patient; Premanifest HD expanded gene carrier

Clinical measures DIAGNOSTIC_TEST

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

Early Manifest HD patient; Healthy controls; Moderate Manifest HD patient; Premanifest HD expanded gene carrier

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Brighton & Sussex Medical School: collaborator
• University of Ulm: collaborator

Study Sites (1)

Leiden University Medical Centre

Leiden, South Holland, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood and CSF (collected in a fasted state)

MeSH Terms

Conditions

Huntington Disease; Nerve Degeneration; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation

Study Officials

• Susanne de Bot, MD PhD

  Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: September 9, 2022
• Study Start: August 11, 2021
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2024
• Last Updated: September 9, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)