Nigrosomal Iron Imaging in Parkinson's Disease

NCT ID: NCT03022357

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 145 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-05-31

Brief Summary

Prospective observational study to compare sensitivity of 3T functional Magnetic Resonance Imaging (3T fMRI) at diagnosing Parkinson's Disease (PD) against the benchmark DaTScan diagnostic test and clinical diagnosis at follow up.

Detailed Description

Idiopathic Parkinson's is characterized by loss of midbrain dopaminergic neurons preferentially affecting the nigrosomes of the pars compacta of the substantia nigra (SNpc). At the time of clinical diagnosis, an estimated 50-70% of the neurons of the SNpc are lost. Non-invasive imaging of cell loss in the nigrosomes containing the SNpc dopaminergic neurons would be clinically desirable for accurate diagnosis in clinically uncertain cases of parkinsonism, especially in the early stages of Parkinson's. Investigators recently discovered that high resolution susceptibility weighted MRI at 7T and 3T demonstrates iron related signal loss of the NS1 in Parkinson's. These studies proved the feasibility and potential of in vivo nigrosome MRI as new diagnostic tool for Parkinson's. Further support of and confidence in our novel diagnostic concept comes from similar observations by other research groups.

Project goals To establish whether nigrosome MRI is an alternative to DatScanTM in the diagnosis of early Parkinson's in patients with diagnostic uncertainty.

To establish whether nigrosomal iron predicts the severity of Parkinson's. As a secondary aim the investigators will study if nigrosomal iron load as determined by susceptometry correlates to disease severity (MDS-UPDRS).

TRIAL / STUDY OBJECTIVES AND PURPOSE

PURPOSE

• To establish whether nigrosome MRI is an alternative to DatScan in the diagnosis of early Parkinson's
• To establish whether nigrosomal iron predicts the severity of Parkinson's.

PRIMARY OBJECTIVE Validation of NS1 MRI as a qualitative diagnostic marker in early Parkinson's

• To investigate whether the presence or absence of the swallow tail on nigrosome MRI at 3T is as accurate as DatScan and at least 80% sensitive and 80% specific to predict the final clinical diagnosis of Parkinson's vs. other movement disorder in patients with indeterminate or atypical parkinsonian features.

Hypothesis 1: That the swallow tail sign is an accurate marker of early Parkinson's

SECONDARY OBJECTIVES Biomarker discovery based on quantitative nigrosome iron markers in Parkinson's • To investigate whether diagnostic performance of nigrosome MRI can be further improved through quantitative assessment of nigrosomal iron and combination with neuromelanin metrics.

Hypothesis 2: That nigrosomal iron metrics further improve the detection of early Parkinson's

• To assess how well disease severity can be predicted by iron content in the nigrosome and by a combination of iron content and the size of the neuromelanin-rich nigra volume.

Hypothesis 3: That nigrosomal iron metrics are closely associated with severity of early Parkinson's

The investigators will be recruiting 145 patients with diagnostic uncertainty of Parkinson's Disease. These patients will undergo a MRI and DATscans and will be clinically examined. They will then be followed-up (clinical examination) in 12 months, identifying if they can be confirmed as having Parkinson's Disease, in order to compare the sensitivity and specificity of nigrosome1 detected by MRI with DATScan, potentially allowing a non-invasive and much less expensive means of diagnosing Parkinson's Disease.

Conditions

Parkinson Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Patient assessment

Clinical examination, Examination, Questionnaires

Intervention Type: OTHER

DATScan

In small subgroup

Intervention Type: RADIATION

Orbital X-Ray

If foreign body in eye needs exclusion

Intervention Type: RADIATION

Magnetic Resonance Imaging (MRI)

MRI scanning of all subjects

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Ability to give informed consent
• Age > 21 to < 90 years
• Clinical symptoms suspicious for a diagnosis of Parkinson's disease but clinical uncertainty with regards to a definite diagnosis:

• Clinical symptoms not meeting all of the required UK brain bank diagnostic criteria for the diagnosis of PD
• 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 NHS clinical diagnostic workup to investigate a suspicion for a parkinsonian movement disorder type disease or referred for a research DatScan as part of this study for the diagnostic workup to investigate a suspicion for a parkinsonian movement disorder type disease.

Exclusion Criteria

• Participants with any known contraindication to MRI such as:

• Intracranial aneurysm clips
• Cardiac pacemakers and defibrillators
• Cochlear implants.
• MR-incompatible metal implant or tattoo
• Patients with a significant head tremor
• Claustrophobia
• Pregnant women
• Participants that are felt to be unfit for the MRI scan according to the judgement of medically qualified personnel, either on the research team, or the patient's clinical team. (eg. due to back pain, claustrophobia, acute sickness etc.) This includes patients with signs of impaired temperature regulation such as an extremely high fever.
• (only for those planned for research DatScan) Participants in which a DatScan nuclear medical study can't be performed due to

• Severe allergy to iodide compounds
• Thyroid gland dysfunction

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dorothee Auer (Principal Investigator)

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Stefan Schwarz (Co-Principal Investigator)

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

Royal Derby Hospital

Derby, Derbyshire, United Kingdom

Site Status: NOT_YET_RECRUITING

Imperial College London

London, , United Kingdom

Site Status: NOT_YET_RECRUITING

University of Nottingham

Nottingham, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Dorothee Auer

Role: CONTACT

dorothee.auer@nottingham.ac.uk

01158 231178

Stefan Schwarz

Role: CONTACT

stefan.schwarz@nottingham.ac.uk

029 2074 7747

Facility Contacts

Rob Skelly

Role: primary

rob.skelly@nhs.net

01332 340131

Antonio M Batisda

Role: primary

a.martin-bastida@imperial.ac.uk

+44 (0)20 7589 5111

Dorothee Auer

Role: primary

dorothee.auer@nottingham.ac.uk

Stefan Schwarz

Role: backup

stefan.schwarz@nottingham.ac.uk

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Related Links

http://www.ncbi.nlm.nih.gov/books/NBK48502/

NICE Guideline (UK). Diagnosing Parkinson's disease. 2006 \[cited 2015 Jul 31\]

Other Identifiers

16048

Identifier Type: -

Identifier Source: org_study_id