Neuromelanin MRI: A Progression Marker in Early PD

Parkinson Disease Clinical Trial

— InsIghtPD  

Official title:

In Vivo Serial Neuromelanin MRI to Assess Depigmentation Rates in the Substantia Nigra of Early Parkinson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05631158
• Other study ID #: 281685
• Status: Recruiting
• Start date: November 1, 2020
• Est. completion date: July 2024

Study information

• Verified date: March 2022
• Source: University of Nottingham
• Contact: Yue (Lily) Xing, PhD
• Phone: 44-01158232877
• Email: Yue.Xing[@]nottingham.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

-Inclusion criteria for patients:

• 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

Inclusion criteria for healthy controls:

• Age =18 to <90years
• Being able and willing to provide informed consent

Exclusion Criteria:

• Exclusion criteria for patients:

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

6. The presence of UK Brain Bank exclusion criteria will be recorded at baseline, allowing for the presence of 1 or 2 exclusion criteria (e.g. dopamine antagonist Drug used; more than one affected relative) (if justified e.g. by abnormal SPECT).

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.

Exclusion criteria for healthy controls:

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.

Related Conditions & MeSH terms

• Disease Progression
• Parkinson Disease
• Progression, Disease

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
United Kingdom	University of Nottingham	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuromelanin signal in PD	The primary outcome measure of this study is the neuromelanin-related signal on dedicated 3T MRI.	6 months
Secondary	Depigmentation rates	differences in depigmentation rates between Parkinson's and controls in extended retrospective cohorts (discovery); to assess whether earlier depigmentation rates can predict longer term clinical change based on commonly used outcome markers in clinical trials	2 years