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N3iPD: Nigrosomal Iron Imaging in Parkinson's Disease

Sponsor
University of Nottingham (Other)
Overall Status
Unknown status
CT.gov ID
NCT03022357
Collaborator
Michael J. Fox Foundation for Parkinson's Research (Other), National Institute for Health Research, United Kingdom (Other)
145
Enrollment
3
Locations
35
Duration (Months)
48.3
Patients Per Site
1.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: Patient assessment
  • Radiation: DATScan
  • Radiation: Orbital X-Ray
  • Other: Magnetic Resonance Imaging (MRI)

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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
145 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Nigrosomal Iron Imaging in Parkinson's Disease
Study Start Date :
Jun 1, 2016
Anticipated Primary Completion Date :
Apr 1, 2019
Anticipated Study Completion Date :
May 1, 2019

Outcome Measures

Primary Outcome Measures

  1. Presence or absence of "swallow tail" on nigrosome MRI at 3T [12 months]

    Does absence of "swallow tail" on nigrosome MRI at 3T correlate with final diagnosis of Parkinson's Disease 12 months after initial presentation of clinically uncertain diagnosis? Is this correlation as accurate as that of DatScan? Is nigrosome MRI at 3T at least 80% sensitive and 80% specific to predict the final clinical diagnosis of Parkinson's disease vs. other movement disorders in patients with indeterminate or atypical parkinsonian features? Is the "swallow tail" and accurate marker of early Parkinson's disease.

Eligibility Criteria

Criteria

Ages Eligible for Study:
21 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Royal Derby Hospital Derby Derbyshire United Kingdom DE22 3NE
2 Imperial College London London United Kingdom SW7 2AZ
3 University of Nottingham Nottingham United Kingdom NG7 2RD

Sponsors and Collaborators

  • University of Nottingham
  • Michael J. Fox Foundation for Parkinson's Research
  • National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Dorothee Auer (Principal Investigator), University of Nottingham
  • Principal Investigator: Stefan Schwarz (Co-Principal Investigator), University of Nottingham

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
University of Nottingham
ClinicalTrials.gov Identifier:
NCT03022357
Other Study ID Numbers:
  • 16048
First Posted:
Jan 16, 2017
Last Update Posted:
Oct 12, 2018
Last Verified:
Jan 1, 2017
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Parkinson Disease

Study Results

No Results Posted as of Oct 12, 2018