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Unravelling the Alteration of Brain Structure and Function in Parkinson´s Disease With Ultra-high Field MRI (7TPD)

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ClinicalTrials.gov Identifier: NCT03866044
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : March 7, 2019
Sponsor:
Collaborator:
Bispebjerg Hospital
Information provided by (Responsible Party):
Danish Research Centre for Magnetic Resonance

Brief Summary:

Parkinson's Disease (PD) is a neurodegenerative disease characterized by a range of disabling motor- and non-motor symptoms caused by a loss of neurons in neuromodulatory brainstem nuclei. Typical motor symptoms include bradykinesia, rigidity and tremor. Non-motor symptoms are diverse and include REM sleep behaviour disorder, hyposmia, autonomic dysfunction, depression, apathy and cognitive impairment. The motor symptoms can in some degree be attributed to degeneration of the substantia nigra (SN) and a deficiency of dopamine (DA) availability, and DA replacement therapy can partially alleviate motor symptoms. The role of nigral degeneration on non-motor symptoms is however less clear. In addition to nigral degeneration, the noradrenergic (NA) locus coeruleus (LC) also undergoes severe degeneration in PD. Again, it is unclear how LC degeneration contributes to motor and non-motor symptoms.

Ultra-high resolution structural magnetic resonance imaging (MRI) provides the opportunity to assess alterations of the affected nuclei in detail and functional MRI (fMRI) can map activation in the neuronal populations as a measure of DA and NA function.


Condition or disease
Parkinson Disease

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Unravelling the Alteration of Brain Structure and Function in Parkinson´s Disease With Ultra-high Field MRI
Actual Study Start Date : September 19, 2018
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : August 1, 2020

Resource links provided by the National Library of Medicine


Group/Cohort
Parkinson's Disease (PD)

Patients with Parkinson's Disease meeting the following criteria:

Inclusion criteria:

  • Aged 18 or more.
  • Clinically established or probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease
  • Signed informed consent

Exclusion criteria:

  • Pregnancy or breastfeeding
  • History of other neurologic or psychiatric disease
  • Pacemaker or other implanted electronic devices
  • Claustrophobia
Healthy participants

Healthy participants age- and sex-matched to the PD group.

Inclusion criteria:

  • Age- and sex-matched to PD group (aged 18 or more)
  • Signed informed consent

Exclusion criteria:

  • Pregnancy or breastfeeding
  • History of neurologic or psychiatric disease
  • Pacemaker or other implanted electronic devices
  • Claustrophobia



Primary Outcome Measures :
  1. SN contrast ratio on neuromelanin sensitive images [ Time Frame: Baseline ]
    Mean SI(SN)/mean SI(cerebral peduncles), SI=signal intensity. We expect that PD patients will have decreased SN contrast ratio compared with age-matched healthy participants and that SN contrast ratio will correlate with UPDRS-3 subscore.

  2. SN volume on neuromelanin sensitive images [ Time Frame: Baseline ]

    Voxels in SN with mean SI > SI+2 standard deviations(cerebral peduncles) , SI=signal intensity).

    We expect that PD patients will have decreased SN volume compared with age-matched healthy participants and that SN volume will correlate with UPDRS-3 subscore.


  3. LC contrast ratio on neuromelanin sensitive images [ Time Frame: Baseline ]
    Mean SI(LC)/mean SI(pontine tegmentum), SI=signal intensity. We expect that PD patients will have decreased LC contrast ratio compared with age-matched healthy participants and that LC contrast ratio will correlate with NMSS, LARS and BDI-II scores.

  4. LC volume on neuromelanin sensitive images [ Time Frame: Baseline ]

    Voxels in LC with mean SI > SI+4 standard deviations(pontine tegmentum), SI=signal intensity).

    We expect that PD patients will have decreased LC volume compared with age-matched healthy participants and that LC volume will correlate with NMSS, LARS and BDI-II scores.


  5. Total SN iron accumulation: SWI [ Time Frame: Baseline ]
    SN mean signal intensity on SWI. We expect that PD patients will have lower mean SN SWI signal intensity compared to healthy.

  6. Total SN iron accumulation: R2* [ Time Frame: Baseline ]
    SN mean R2* values (unit=1/s). We expect that PD patients will have higher mean SN R2* values compared to healthy.

  7. Total SN iron accumulation: QSM [ Time Frame: Baseline ]
    SN mean QSM values (unit=ppb). We expect that PD patients will have higher mean SN QSM values compared to healthy.

  8. Nigrosome-1 iron accumulation: SWI [ Time Frame: Baseline ]
    Nigrosome-1 signal visibility on SWI assessed by blinded raters. We expect that iron accumulation in nigrosome-1 will be greater in PD patients leading to a loss of discrimination on SWI.

  9. Nigrosome-1 iron accumulation: R2* [ Time Frame: Baseline ]
    Mean R2* values in the nigrosome-1 region (unit=1/s). We expect that PD patients will have higher R2* values in the nigrosome-1 region.

  10. Nigrosome-1 iron accumulation: QSM [ Time Frame: Baseline ]
    Mean QSM values in the nigrosome-1 region (unit=ppb). We expect that PD patients will have higher QSM values in the nigrosome-1 region.

  11. Functional brain activation pattern in the LC, SN, VTA, and striatum [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]

    Revealed by task related blood oxygenation level dependent (BOLD) signal changes.

    We expect that functional activation in these regions will be attenuated in PD patients corresponding to their loss of brainstem nuclei integrity (see hypotheses).


  12. Motor disease severity [ Time Frame: Baseline ]
    Unified Parkinson's Disease Rating Scale (UPDRS)-3 subscore (Motor severity, range 0-108, higher values = worse outcome). Measured while subjects are taking their usual medication.

  13. Overall disease severity [ Time Frame: Baseline ]
    Total Unified Parkinson's Disease Rating Scale (UPDRS) score (sum of all 4 subscores listed below, range 0-199, higher values = worse outcome), UPDRS-1 (Cognitive and mental disease severity, range 0-16, higher values = worse outcome), UPDRS-2 (disease severity in relation to activities of daily living, range 0-52, higher values = worse outcome) and UPDRS-3 (Motor severity, range 0-108, higher values = worse outcome), UPDRS-4 (Complications of therapy, range 0-23, higher values = worse outcome) subscores. Measured while subjects are taking their usual medication.

  14. Non-motor disease severity [ Time Frame: Baseline ]
    Total Non-Motor Symptom Scale (NMSS) score (range 0-360, higher values = worse outcome). Measured while subjects are taking their usual medication.

  15. Modified Hoehn and Yahr Staging [ Time Frame: Baseline ]
    Modified Hoehn and Yahr Staging (Crude measure of disease severity, range 0-5, higher score = worse outcome). Measured while subjects are taking their usual medication.

  16. Schwab and England Activities of Daily Living Scale [ Time Frame: Baseline ]
    Schwab and England Activities of Daily Living Scale (Measure of ADL function, range 100-0%, higher score = better outcome). Measured while subjects are taking their usual medication.

  17. Apathy [ Time Frame: Baseline ]
    Total Lille Apathy Rating Scale (LARS) score (range -36-36, higher score = better outcome).

  18. Mood [ Time Frame: Baseline ]
    Total Beck's Depression Inventory-II (BDI-II) score (range 0-63, lower score = better outcome).

  19. Autonomic emotional-arousal response: Pupillary response [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]

    Change in pupil size in response to emotionally arousing stimuli compared with non-arousing stimuli (unit=difference in mm).

    We expect that PD patients will have a smaller difference in pupillary response between arousing and non-arousing stimuli compared to healthy participants.


  20. Autonomic emotional-arousal response: Skin conductance response [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]

    Change in skin conductance (unit=micro Siemens) in response to emotionally arousing stimuli compared with non-arousing stimuli.

    We expect that PD patients will show an attenuated skin conductance response to arousing stimuli compared to healthy participants.


  21. Behavioural outcome measures: Choices [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]
    Learning in reinforcement learning paradigm: Choices, reaction times, parameters describing degree of action-value vs. stimulus value learning from computational model.

  22. Behavioural outcome measures: Reaction times [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]
    Learning in reinforcement learning paradigm: Reaction times (unit=ms) describing degree of action-value vs. stimulus value learning from computational model.

  23. Behavioural outcome measures: Model parameters [ Time Frame: ON & OFF PD medication in a period within 24 weeks from baseline. ]
    Learning in reinforcement learning paradigm: Model parameters describing degree of action-value vs. stimulus value learning from computational model.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Participants will be recruited from the ambulatory care at the Department of Neurology, Bispebjerg Hospital and through private practicing neurologists. As part of the clinical assessment relevant patients with PD will be asked if they would be interested in participating in the study. Also, letters with invitation to participate in the study will be sent to patients with PD in treatment at the clinics. Participants will also be recruited from the general population via advertisements.
Criteria
  1. Parkinson's Disease (PD) group

    Inclusion criteria:

    • Aged 18 or more.
    • Clinically established or probable PD according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease
    • Signed informed consent

    Exclusion criteria:

    • Pregnancy or breastfeeding
    • History of other neurologic or psychiatric disease
    • Pacemaker or other implanted electronic devices
    • Claustrophobia
  2. Healthy participants age- and sex-matched to the PD group:

Inclusion criteria:

  • Age- and sex-matched to PD group (aged 18 or more)
  • Signed informed consent

Exclusion criteria:

  • Pregnancy or breastfeeding
  • History of neurologic or psychiatric disease
  • Pacemaker or other implanted electronic devices
  • Claustrophobia

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): NCT03866044


Contacts
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Contact: Christopher F Madelung, MD 38620436 christopher.fugl.madelung.01@regionh.dk
Contact: Hartwig R Siebner, DMSci 38626541 hartwig.roman.siebner@regionh.dk

Locations
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Denmark
Danish Research Centre For Magnetic Resonance, Copenhagen University Hospital Hvidovre Recruiting
Hvidovre, Denmark, 2650
Contact: Christopher F Madelung, MD    38620436    christopher.fugl.madelung.01@regionh.dk   
Contact: Hartwig R Siebner, DMSci    38626541    hartwig.roman.siebner@regionh.dk   
Principal Investigator: Hartwig R Siebner, DMSci         
Sub-Investigator: Christopher F Madelung, MD         
Sub-Investigator: David Meder, PhD         
Department of Neurology, Copenhagen University Hospital Bispebjerg Recruiting
København, Denmark, 2400
Contact: Annemette Løkkegaard, MD, PhD         
Sub-Investigator: Annemette Løkkegaard, MD, PhD         
Sponsors and Collaborators
Danish Research Centre for Magnetic Resonance
Bispebjerg Hospital
Investigators
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Principal Investigator: Hartwig R Siebner, DMSci Danish Research Centre for Magnetic Resonance

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Responsible Party: Danish Research Centre for Magnetic Resonance
ClinicalTrials.gov Identifier: NCT03866044     History of Changes
Other Study ID Numbers: H-18021857
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases