Neuromelanin MRI: A Progression Marker in Early PD

NCT ID: NCT05631158

Last Updated: 2022-11-30

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

135 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-01

Study Completion Date

2024-07-31

Brief Summary

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Prospective observational study to qualify NM-MRI as progression marker in early Parkinson's.

Detailed Description

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Parkinson's is the second most common neurodegenerative disorder with progressive, disabling motor and non- motor symptoms for which effective symptomatic, but non disease-modifying treatment is available. Neuromelanin- containing neurons in the substantia nigra undergo neurodegeneration during Parkinson's disease. There is considerable heterogeneity in the progression of cell loss and clinical symptoms with major research interest in identifying prognostic subtypes.

A non-invasive biomarker that can track the loss of the neuromelanin-containing neurons would be highly desirable to (i) study subtype-specific trajectories of SN depigmentation, (ii) track disease progression in early Parkinson's to assist in stratifying groups and outcome assessment in clinical intervention trials, and (iii) enable patients and their families to better manage their condition including informed forward planning. Neuromelanin MRI (NM-MRI) is a new approach sensitive to the neuromelanin-iron complex, with proven association with the tissue changes of the number of the neuromelanin-containing neurons. Its diagnostic value was established in several studies case-control, but there is a lack of standardisation, multi-centre studies and prospective diagnostic trials. To date only a small, single arm retrospective study reported serial NM loss in Parkinson's.

Building on our previous work, the proposed research entails the development of an early progression biomarker for Parkinson's disease that is pathologically relevant, non-invasive, and uses MRI which is a widely available imaging method for detection. The experimental approach combines advanced computational imaging, retrospective use and extension of existing cohorts with a new dedicated prospective serial study using NM-MRI in uncertain parkinsonism, de novo and early Parkinson and healthy controls using latest MRI technology.

Conditions

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Parkinson Disease Progression, Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Early Parkinson's disease

All the participants will undergo five clinical examination, four MRI scans and one fasting blood test in total in this serial study.

MRI

Intervention Type DIAGNOSTIC_TEST

The clinical examination includes a short physical exam, a brief history of allergies, previous diseases and medications, and disease-related questionnaires.

All the participants will undergo 4 serial MRI scans: one MRI scan at the baseline visit, 6, 12, 18 months follow-up visit, respectively to record the changes in the brain, which include the neuromelanin scan.

For future proving the value of our study, we will also collect and store blood samples at the initial visit.

Healthy Controls

This cohort will undergo the same procedure of the patient's group.

MRI

Intervention Type DIAGNOSTIC_TEST

The clinical examination includes a short physical exam, a brief history of allergies, previous diseases and medications, and disease-related questionnaires.

All the participants will undergo 4 serial MRI scans: one MRI scan at the baseline visit, 6, 12, 18 months follow-up visit, respectively to record the changes in the brain, which include the neuromelanin scan.

For future proving the value of our study, we will also collect and store blood samples at the initial visit.

Interventions

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MRI

The clinical examination includes a short physical exam, a brief history of allergies, previous diseases and medications, and disease-related questionnaires.

All the participants will undergo 4 serial MRI scans: one MRI scan at the baseline visit, 6, 12, 18 months follow-up visit, respectively to record the changes in the brain, which include the neuromelanin scan.

For future proving the value of our study, we will also collect and store blood samples at the initial visit.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Blood test Physical examination

Eligibility Criteria

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Inclusion Criteria

* For Parkinson's patients and early-onset Parkinson's:

1. Diagnosis of Parkinson's disease, based on UK Brain Bank criteria and made within the preceding 3 years ('recent onset cases'); or
2. diagnosed at under 50 years ('under 50 years cases')
* For clinical symptoms suspicious for a diagnosis of PD but clinical uncertainty with regard to a definite diagnosis:

1. clinical symptoms not meeting all of the required UK Brain Bank diagnostic criteria for the diagnosis of PD; or
2. clinical features not typically associated with PD and therefore raising the possibility of a different type disorder/movement disorder referred for a DaTSCAN as part of the National Health Service (NHS) clinical diagnostic work-up to investigate a suspicion for a parkinsonian movement disorder-type disease, or referred for a research DaTSCAN as part of existing N3iPD and PaMIR studies for the diagnostic work-up to investigate a suspicion for a parkinsonian movement disorder-type disease.
* Age ≥18 to \<90years
* Being able and willing to provide informed consent


* Age ≥18 to \<90years
* Being able and willing to provide informed consent

Exclusion Criteria

1. The patient has severe comorbid illness that would prevent full study participation
2. The patient has features indicating another type of degenerative parkinsonism, e.g. progressive supranuclear palsy
3. Drug-induced parkinsonism (Drug-unmasked PD is allowed)
4. Symmetrical lower body parkinsonism attributable to significant cortical and/or subcortical cerebrovascular disease (patients with 'incidental' small vessel disease on brain imaging are allowed).
5. Negative or normal functional imaging of the presynaptic dopamine system
7. Any contraindication to Magnetic Resonance (MR) scanning.
8. Any major neurological (other than PD), psychiatric or cardiovascular disease or history of brain injury.
9. Medical illness or medication that may affect brain morphometry or function.
10. Patient who is pregnant and/or breastfeeding.


1. Subject has severe comorbid illness that would prevent study participation
2. Subject already has a diagnosis of Parkinson's disease
3. Any contraindication to Magnetic Resonance (MR) scanning
4. Subject who is pregnant and/or breastfeeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Nottingham

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Nottingham

Nottingham, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Yue (Lily) Xing, PhD

Role: CONTACT

Phone: 44-01158232877

Email: [email protected]

Dorothee Auer, MD PhD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Yue (Lily) Xing, PhD

Role: primary

Other Identifiers

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281685

Identifier Type: -

Identifier Source: org_study_id