Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

Mitochondrial Diseases Clinical Trial

Official title:

Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03572114
• Other study ID #: 18/0075
• Secondary ID: IRAS ID 243171
• Status: Not yet recruiting
• Start date: July 1, 2018
• Est. completion date: July 1, 2021

Study information

• Verified date: June 2018
• Source: University College, London
• Contact: Sebastian R Schreglmann, MD
• Phone: 0203448 8604
• Email: skgtsrs[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dystonia
• Dystonia, Familial
• Dystonic Disorders
• Mitochondrial Diseases
• Nerve Degeneration
• Neurodegeneration With Brain Iron Accumulation 5
• Pantothenate Kinase-Associated Neurodegeneration
• Parkinson Disease
• Parkinson Disease, Juvenile
• Parkinsonian Disorders
• Sporadic Dystonia

Intervention

Diagnostic Test:
• 3Tesla MRI
A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes). 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo) conventional FLAIR sequence

Behavioral:
• Burke-Fahn-Marsden Dystonia Rating scale
internationally standardized examination/quantification of dystonia
• MDS-United Parkinsons Disease Rating Scale, Part III
most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society
• Beck Depression Inventory
internationally standardized examination to quantify traits of anxiety and depression
• MoCA: Montreal Cognitive Assessment:
internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	neuromelanin content	absolute amount of neuromelanin in midbrain, striatum and other areas of the brain	up to 8 weeks
Secondary	neuromelanin association	correlate neuromelanin quantification with demographic and clinical details	up to 8 weeks
Secondary	iron association	correlate neuromelanin quantification with demographic and clinical details	up to 8 weeks
Secondary	Iron content	absolute amount of iron in midbrain, striatum and other areas of the brain	up to 8 weeks