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Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

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ClinicalTrials.gov Identifier: NCT03572114
Recruitment Status : Not yet recruiting
First Posted : June 28, 2018
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:
To generate pilot data to investigate the potential to use in vivo iron- and neuromelanin-quantification as imaging tools for the diagnostic evaluation of movement disorders with predominant dystonia / parkinsonism. To this end we are planning to compare the MR imaging neuromelanin and iron-pattern and content in midbrain, striatum and further brain structures in clinically similar entities and respective, sex- and age-matched healthy controls.

Condition or disease Intervention/treatment
Sporadic Dystonia Dystonia, Familial Parkinson Disease, Juvenile Neurodegeneration With Brain Iron Accumulation 5 Mitochondrial Diseases Diagnostic Test: 3Tesla MRI Behavioral: Burke-Fahn-Marsden Dystonia Rating scale Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III Behavioral: Beck Depression Inventory Behavioral: MoCA: Montreal Cognitive Assessment:

Detailed Description:

Iron- or Neuromelanin-sensitive MR-imaging has not been consistently applied to the study of syndromes presenting with predominant dystonia/parkinsonism yet. We are planning to study the following groups, as they can often be very difficult to be distinguished from PD and in particular young-onset PD, on clinical grounds only:

  • Dopa-responsive dystonia (DRD) can present similar to young-onset PD, but carries a completely different prognosis, necessitating different treatment requirements due to fundamentally different underlying physiology.
  • Sporadic and Inherited dystonias (i.e. due to TorsinA (DYT1) and other gene mutations) often present with dystonia, particularly affecting the leg, which is clinically indistinguishable from young-onset PD.
  • Young-onset PD, i.e. PD presenting with motor symptoms before 45 years of age, caused by a familiar gene mutation (PARKIN, Pink, DJ-1, PLA2G6, FBX07, ATP13A2, VPS13C, RAB39B, Lubag), often presents with predominant dystonia, particularly with leg-onset.
  • NBIAs present with dystonia/parkinsonism: while basal ganglia iron accumulation is a known hallmark feature of the condition [3], the characteristics of neuromelanin regulation are unknown.
  • Mitochondrial disease presenting with dystonia / parkinsonism (such as for example Leigh syndrome due to mutations in the Surf-1 gene or mutations m.3243A>G or POLG) [4]
  • Respective age- and sex-matched healthy controls This study is designed to produce pilot data on these disease entities. By potentially accelerating the diagnostic process and identification of disease entities, neurologists might be able to deliver more selective and dedicated treatment.

Furthermore, combining Neuromelanin- and iron-specific imaging will offer the possibility to study the condition- specific dynamics of iron homeostasis in these rare conditions.

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Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Imaging Neuromelanin and Iron in Dystonia/Parkinsonism
Estimated Study Start Date : July 1, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021


Group/Cohort Intervention/treatment
Sporadic Dystonia
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Familial Dystonia
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Parkinson´s disease, juvenile
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Neurodegeneration with brain iron acc.
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

mitochondrial disease
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Healthy Controls
3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment
Diagnostic Test: 3Tesla MRI
  1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content
  2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes).
  3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo)
  4. conventional FLAIR sequence

Behavioral: Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia

Behavioral: MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society

Behavioral: Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression

Behavioral: MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism




Primary Outcome Measures :
  1. neuromelanin content [ Time Frame: up to 8 weeks ]
    absolute amount of neuromelanin in midbrain, striatum and other areas of the brain


Secondary Outcome Measures :
  1. neuromelanin association [ Time Frame: up to 8 weeks ]
    correlate neuromelanin quantification with demographic and clinical details

  2. iron association [ Time Frame: up to 8 weeks ]
    correlate neuromelanin quantification with demographic and clinical details

  3. Iron content [ Time Frame: up to 8 weeks ]
    absolute amount of iron in midbrain, striatum and other areas of the brain



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients from the National Hospital of Neurology, Queen Square, movement disorder outpatient clinic;
Criteria

Inclusion Criteria:

  • clinical diagnosis of parkinsonism and/or dystonia due to
  • dopa-responsive dystonia
  • sporadic or inherited/genetic dystonia
  • young-onset Parkinson's disease
  • NBIA
  • Mitochondrial disease

    • OR healthy controls
    • 18 to 60 years of age
    • able to give informed consent

Exclusion Criteria:

  • Inability to tolerate 35min in an MRI machine
  • Participated in a clinical drug trial up to 28 days before inclusion into the present study
  • Contra-indications to 3T MRI on MRI safety grounds, such as presence of contra-indicated medical implants, as according to the established routine operating procedures for clinical MRI in the Lysholm Department of Neuroradiology at the National Hospital for Neurology and Neurosurgery.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03572114


Contacts
Layout table for location contacts
Contact: Sebastian R Schreglmann, MD 0203448 8604 skgtsrs@ucl.ac.uk
Contact: Bhatia P Kailash, MD, DM, FRCP 0203448 4252 k.bhatia@ucl.ac.uk

Sponsors and Collaborators
University College, London
Investigators
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Principal Investigator: Bhatia P Kailash, MD, DM, FRCP UCL, Institute of Neurology, Sobell Department
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT03572114    
Other Study ID Numbers: 18/0075
IRAS ID 243171 ( Other Identifier: UCL R&D )
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Dystonia
Dystonic Disorders
Parkinsonian Disorders
Pantothenate Kinase-Associated Neurodegeneration
Mitochondrial Diseases
Nerve Degeneration
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dyskinesias
Neurologic Manifestations
Pathologic Processes
Metabolic Diseases
Neuroaxonal Dystrophies
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn