Parkinson's Disease (PD)NCT01888185
Identifying Biomarkers of Parkinson's Disease Using Magnetic Resonance Imaging (MRI)
An observational study of Parkinson's Disease (PD) and Parkinsonism, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease (PD), Parkinsonism, Progressive Supranuclear Palsy (PSP)
- How many people
- 290 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Clinical patients and community volunteers
Who may be able to join
- PD Subjects:
- 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.
- MMSE score of 15 or greater unless a legal representative is present.
- Idiopathic PD according to published criteria.
- History of adequate response to dopaminergic therapy.
- History of asymmetrical symptom onset
Show all 22Show fewer
- MSA Subjects:
- Older than 30 yrs.
- 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.
- MMSE score of 15 or greater unless a legal representative is present.
- MSA according to published criteria.
- History of autonomic \& urinary dysfunction and/or severe cerebellar ataxia.
- PSP Subjects:
- Older than 40 yrs.
- 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.
- PSP according to published criteria.
- Vertical gaze palsy and/or slow vertical gaze/postural instability during first year of diagnosis.
- MMSE score of 15 or greater unless a legal representative is present
- Controls:
- Older than 21 yrs.
- Able and willing to sign the consent form.
- MMSE greater than 24.
Who cannot join
- PD Subjects:
- Unable or does not have a legal representative/unwilling to provide consent.
- Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- History of cerebrovascular diseases or other neurological disorders.
- Major medical problems such as renal or liver failure.
- Unstable, non-PD-related medical conditions.
Show all 36Show fewer
- MMSE score less than 15 unless a legal representative is present
- Use of anticoagulant medications.
- Signs of dementia.
- MSA Subjects:
- Unable or does not have a legal representative /unwilling to provide consent.
- Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- History of cerebrovascular diseases or other neurological disorders.
- Major medical problems such as renal or liver failure.
- Unstable, non-MSA-related medical conditions.
- MMSE score less than 15 unless a legal representative is present
- Use of anticoagulant medications.
- Signs of dementia.
- PSP Subjects:
- Unable or does not have a legal representative /unwilling to provide consent.
- Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- History of cerebrovascular diseases or other neurological disorders.
- Major medical problems such as renal or liver failure.
- Unstable, non-PSP-related medical conditions.
- MMSE score less than 15 unless a legal representative is present
- Use of anticoagulant medications.
- Signs of dementia.
- Controls:
- Unable/unwilling to provide consent.
- Evidence of severe memory impairment or signs of dementia (MMSE < 24).
- Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- History of cerebrovascular diseases or other neurological disorders.
- Major medical problems such as renal or liver failure.
- Unstable medical conditions.
- Use of anticoagulant medications.
- Signs of dementia.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center and College of Medicine
Hershey, Pennsylvania, 17033
About this study
Official title: 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).
Read the detailed description
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.
- Conditions
- Parkinson's Disease (PD), Parkinsonism, Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA)
- Keywords
- Parkinson's, PD, nigrostriatal, substantia nigra, MRI, DTI, FA, R2*, Parkinson's Disease Biomarkers Program, PDBP, ferritin, transferrin, Fe, iron protein, PSP, MSA
- Medical subject headings
- Parkinson Disease, Parkinsonian Disorders, Supranuclear Palsy, Progressive, Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
Substantia Nigra (SN) FA and R2* values in PD subjects will be compared with control subjects and correlated with clinical and behavioral measures.
Measured: 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.
Secondary outcomes (3)
Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes
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.
Measured: Assessed at baseline visit.
Iron(Fe)-related proteins in body fluids as biomarkers of PD
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.
Measured: 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
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.
Measured: From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's Disease (PD)Studies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01888185
- Sponsor's protocol ID
- MSHersheyMC-40726
- Status last verified
- Jan 2020
- First submitted
- 17 Jan 2013
- Last updated
- 3 Jan 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal MRI Markers of Nigrostriatal Pathology in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT01888185
- Acronym / sponsor ID
- MSHersheyMC-40726
- Conditions
- Parkinson's Disease (PD), Parkinsonism, Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA)
- Keywords
- Parkinson's, PD, nigrostriatal, substantia nigra, MRI, DTI, FA, R2*
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 290 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 27 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Clinical patients and community volunteers
Key inclusion criteria (22 listed)
- 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.
- MMSE score of 15 or greater unless a legal representative is present.
- Idiopathic PD according to published criteria.
- History of adequate response to dopaminergic therapy.
- History of asymmetrical symptom onset
Key exclusion criteria (36 listed)
- Unable or does not have a legal representative/unwilling to provide consent.
- Any condition that precludes a routine MRI (e.g., claustrophobia, pacemaker, severe scoliosis, etc.).
- History of cerebrovascular diseases or other neurological disorders.
- Major medical problems such as renal or liver failure.
- Unstable, non-PD-related medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression
Time frame: 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.
3 secondary outcomes
Nigrostriatal diffusion tensor imaging (DTI) and R2* differentiate PD from parkinsonian syndromes
Time frame: Assessed at baseline visit.
Iron(Fe)-related proteins in body fluids as biomarkers of PD
Time frame: 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
Time frame: From baseline until date of death from any cause within 5 years for patient participants who succumb to their disease
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2020.
- Parkinson's Disease Biomarkers Program (PDBP) description of studyLink provided by the sponsor.
- Penn State Hershey Neurology homepageLink provided by the sponsor.
Related trials for Parkinson's Disease (PD)
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingObservational study
Striatal and Extra-Striatal Cholinergic Terminal Density in LRRK2-PD Mutation
Parkinson Disease
Not yet recruiting
Unilateral and Staged Bilateral Pallidothalamic Tractotomy Using Exablate MRgFUS in Advanced Parkinson's Disease.
Parkinson Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson's Disease (PD) and Parkinsonism, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differential roles of fractional anisotropy (FA) and R2* in PD detection and progression (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2020.