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Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)

2020. január 2. frissítette: Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center

Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease

This study is designed to determine if magnetic resonance imaging (MRI) measures can be used to diagnose and monitor the progression of Parkinson's disease (PD) while distinguishing between PD and parkinsonisms [conditions that are PD look-a-like diseases such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA)] when combined with changes in certain proteins in body fluids that are related to iron (Fe).

A tanulmány áttekintése

Részletes leírás

The lack of in vivo biomarker(s) reflecting Parkinson's disease (PD)-related cell loss and associated pathoetiological/physiological processes in nigrostriatal structures has hindered discovery research and limited the ability to evaluate disease-modifying therapies. Recent research has generated excitement for using DTI and R2* MRI measures as biomarker(s) for PD-related pathology in nigrostriatal pathways, but they fall short by the lack of understanding of their clinical implications and biological/pathological underpinnings. Working closely with the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Biomarkers Program (PDBP), the proposed work will investigate multimodal MRI techniques in combination with fluid-based iron (Fe) protein profiles to serve as in vivo markers for PD-related nigrostriatal pathology that can be used as biomarkers for diagnosing PD, following its progression, and gaining mechanistic understanding of PD pathoetiology and pathophysiology.

Tanulmány típusa

Megfigyelő

Beiratkozás (Tényleges)

290

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi helyek

    • Pennsylvania
      • Hershey, Pennsylvania, Egyesült Államok, 17033
        • Penn State Milton S. Hershey Medical Center and College of Medicine

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

21 év (Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Igen

Tanulmányozható nemek

Összes

Mintavételi módszer

Nem valószínűségi minta

Tanulmányi populáció

Clinical patients and community volunteers

Leírás

Inclusion Criteria:

PD Subjects:

  1. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
  2. MMSE score of 15 or greater unless a legal representative is present.
  3. Idiopathic PD according to published criteria.
  4. History of adequate response to dopaminergic therapy.
  5. History of asymmetrical symptom onset

MSA Subjects:

  1. Older than 30 yrs.
  2. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
  3. MMSE score of 15 or greater unless a legal representative is present.
  4. MSA according to published criteria.
  5. History of autonomic & urinary dysfunction and/or severe cerebellar ataxia.

PSP Subjects:

  1. Older than 40 yrs.
  2. Able and willing to sign the consent form at time of initial enrollment or if the subject is decisionally impaired and has a legal representative that is able and willing to sign a consent form at the time of the enrollment. If the subject becomes decisionally impaired during the course of the study, their legal representative may sign an addendum to consent for continued participation.
  3. PSP according to published criteria.
  4. Vertical gaze palsy and/or slow vertical gaze/postural instability during first year of diagnosis.
  5. MMSE score of 15 or greater unless a legal representative is present

Controls:

  1. Older than 21 yrs.
  2. Able and willing to sign the consent form.
  3. MMSE greater than 24.

Exclusion Criteria:

PD Subjects:

  1. Unable or does not have a legal representative/unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-PD-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

MSA Subjects:

  1. Unable or does not have a legal representative /unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-MSA-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

PSP Subjects:

  1. Unable or does not have a legal representative /unwilling to provide consent.
  2. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  3. History of cerebrovascular diseases or other neurological disorders.
  4. Major medical problems such as renal or liver failure.
  5. Unstable, non-PSP-related medical conditions.
  6. MMSE score less than 15 unless a legal representative is present
  7. Use of anticoagulant medications.
  8. Signs of dementia.

Controls:

  1. Unable/unwilling to provide consent.
  2. Evidence of severe memory impairment or signs of dementia (MMSE < 24).
  3. Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
  4. History of cerebrovascular diseases or other neurological disorders.
  5. Major medical problems such as renal or liver failure.
  6. Unstable medical conditions.
  7. Use of anticoagulant medications.
  8. Signs of dementia.

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

Kohorszok és beavatkozások

Csoport / Kohorsz
Parkinson's Disease (PD)
Patients with a clinical diagnosis of PD (in various stages)
Progressive supranuclear palsy (PSP)
Patients with a clinical diagnosis of PSP (in various stages)
Multiple system atrophy (MSA)
Patients with a clinical diagnosis of MSA (in various stages)
Controls
Age and gender-matched adults free from neurological disease

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
Időkeret: Change in roles of FA and R2* assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
Substantia Nigra (SN) FA and R2* values in PD subjects will be compared with control subjects and correlated with clinical and behavioral measures.
Change in roles of FA and R2* assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes
Időkeret: Assessed at baseline visit.
DTI and R2* measures in both SN and striatal structures in PD, PSP, MSA and control subjects will be compared to assess sensitivity and specificity of individual and combined MRI measures in diagnosing PD.
Assessed at baseline visit.
Iron(Fe)-related proteins in body fluids as biomarkers of PD
Időkeret: Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
The protein profile in blood, urine, and cerebral spinal fluid (CSF), and their relationships to clinical and MRI measure will be interrogated with the focus being on Fe-related proteins such as hepcidin, ferritin, and transferrin.
Change assessed between baseline and 18 months. Change assessed between baseline and 36 months. Change assessed between 18 and 36 months.
MRI and postmortem pathological correlation
Időkeret: From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease
Postmortem brain analysis on patients who succumb to their disease during the study will be performed in order to inform the relationship of the biomarkers to clinical diagnosis (PD, PSP, MSA) and clinical milestones as well as to inform the pathological underpinnings of the R2* and DTI measures. In addition to standard postmortem diagnostic tests (alpha-synuclein, beta-amyloid, tau, and ubiquitin), total Fe staining, ferritin, hepcidin, tyrosine hydroxylase positive neurons, myelin and glial derived growth factors (glial cell markers) will be assessed in nigrostriatal structures in order to correlate these levels with MRI measures.
From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Publikációk és hasznos linkek

A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete

2012. december 1.

Elsődleges befejezés (Tényleges)

2019. december 1.

A tanulmány befejezése (Tényleges)

2019. december 31.

Tanulmányi regisztráció dátumai

Először benyújtva

2013. január 17.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2013. június 25.

Első közzététel (Becslés)

2013. június 27.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2020. január 3.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2020. január 2.

Utolsó ellenőrzés

2020. január 1.

Több információ

Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .

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