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Retinal Abnormalities as Biomarker of Disease Progression and Early Diagnosis of Parkinson Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02640339
Recruitment Status : Recruiting
First Posted : December 28, 2015
Last Update Posted : December 3, 2019
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date December 22, 2015
First Posted Date December 28, 2015
Last Update Posted Date December 3, 2019
Study Start Date February 2016
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 22, 2015)
  • Retinal nerve fiber layer (RNFL) thickness [ Time Frame: Every 6 months from baseline to 3 years ]
    The results of the RNFL thickness will be expressed in microns in different zones around the optic nerve: temporal, superior, nasal, inferior and global.
  • Retinal ganglion cell layer (GCL) thickness [ Time Frame: Every 6 months from baseline to 3 years ]
    The results of the GCL thickness will be expressed in microns in different zones around the fovea region: temporal- superior, superior, nasal-superior, nasal inferior, inferior, temporal inferior and global.
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02640339 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: December 22, 2015)
  • • Visual Acuity [ Time Frame: Every 6 months from baseline to 3 years ]
    Will be expressed in decimal units
  • • Color Discrimination [ Time Frame: Every 6 months from baseline to 3 years ]
    Will be expressed in decimal units.
  • • Pupillometry [ Time Frame: Every 6 months from baseline to 3 years ]
    Measures will include pupil diameter (expressed in millimeters, in dark and light conditions and the amplitude and velocity of the pupillary response.
  • • Videonystagmography [ Time Frame: Every 6 months from baseline to 3 years ]
    Saccadic velocity and amplitude (expressed in m/seg and degrees) will be measured.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Retinal Abnormalities as Biomarker of Disease Progression and Early Diagnosis of Parkinson Disease
Official Title Retinal Abnormalities as Biomarker of Disease Progression and Early Diagnosis of Parkinson Disease
Brief Summary
  • To determine whether retinal abnormalities, as measured by high definition optical coherence tomography (HD-OCT) and visual electrophysiology techniques can be used as a clinical biomarker to monitor disease progression overtime in patients with Parkinson disease.
  • To establish whether these measures can be used to identify patients with PD in the premotor phase.
  • To define the rate of progression of retinal abnormalities in PD (both in the motor and premotor stages) for potential use as a clinical outcome measure
Detailed Description

The retina is actually brain tissue and is considered part of the central nervous system (CNS). It is the only part of the CNS that can be visualized directly and non-invasively. There is already a body of evidence that retinal neurons accumulate alpha-synuclein and degenerate in Parkinson disease (PD). Whether retinal imaging could be useful as an objective biomarker to track disease progression and response to disease-modifying treatments in patients with PD is not known.

While there are a variety of imaging techniques available (e.g., PET, SPECT, MRI), none of them has emerged as a fully reliable method to accurately measure clinical progression in PD.

The structure of the retina can be studied easily in vivo using spectral domain high definition optical coherence tomography (OCT), a non-invasive imaging technique with a resolution of ~1 microns (0.001 mm). OCT quantifies the thickness of the different retinal layers. The primary aim of this proposal is to determine whether OCT is a reliable clinical measure that can objectively measure clinical progression in PD.

Our group has shown recently that OCT can be used as a means to measure progressive neuronal loss in the retina in patients with a synucleinopathy closely related to PD (multiple system atrophy, MSA). In MSA, retinal degeneration was closely associated with disease severity and progressively worsened overtime in a predictable fashion, sufficient for biostatistical modeling. We now want to find out if this is also true in PD.

There is a panel of non-motor clinical features that increase the risk of developing PD. We propose to measure retinal nerve fiber density in these patients considering them as "pre-motor" PD and follow their clinical evolution overtime. If OCT proves useful as a means to identify pre-motor PD, such a result would present an important therapeutic window to intervene with disease modifying drugs and to prevent the development of CNS deficits.

We plan to determine whether retinal morphology can be correlated with visual function using complementary measures of visual electrophysiology techniques, including pattern electroretinogram (PERG) and photopic negative response (PhNR). These techniques have been used in patients with PD and other synucleinopathies, and do map closely to retinal function abnormalities. But, there is little data describing how these functional measure of the retina progression over time in PD.

We hypothesize that patients with PD have specific patterns of damage in retinal structure and function, that this pattern can be identified in the premotor phase, We believe that OCT can be used as an objective biomarker of premotor diagnosis and disease progression.

INNOVATION:

The structure of the retina presents an ideal opportunity to image the CNS overtime with OCT. As a widely available clinical technique that correlates closely with functional measures of visual electrophysiology, OCT is being increasingly used in multiple sclerosis and other neurodegenerative disorders. If successful, this work may provide a significant tool for the diagnosis of PD in the pre-motor phase and could be used as a clinical outcome measure in disease-modifying trials. To achieve these objectives, we will take advantage of the infrastructure used in the ongoing NIH-funded Natural History of Autonomic Disorders study (ClnicalTrials.gov: NCT01799915), which prospectively follows patients with synucleinopathies with standardized neurological measures overtime. The proposal will provide measures of retinal structure in conjunction with measures of disease severity in a group of patients with well-defined PD. By measuring retinal structure in a group of patients considered high risk for developing PD (namely REM sleep behavior disorder -RBD, and isolated autonomic failure) we will determine the usefulness of OCT as a mean to identify PD in the premotor phase.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population We will select patients from our clinic and take advantage of the infrastructure used in the ongoing NIH-funded Natural History of Autonomic Disorders study (ClnicalTrials.gov: NCT01799915), which prospectively follows patients with synucleinopathies with standardized neurological measures overtime.
Condition
  • Parkinson Disease
  • Multiple System Atrophy
  • REM Sleep Behavior Disorder
  • Pure Autonomic Failure
  • Dementia With Lewy Bodies
Intervention Not Provided
Study Groups/Cohorts
  • Parkinson Disease
    Parkinson's disease is a progressive disorder of the nervous system that affects movement. It develops gradually, with alpha-synuclein deposits in neurons which aggregate into Lewy bodies.
  • Mutiple system atrophy
    is a degenerative neurological disorder. MSA is associated with the degeneration of nerve cells in specific areas of the brain. This cell degeneration causes problems with movement, balance, and autonomic functions of the body such as bladder control or blood-pressure regulation. Neuronal death probably occurs as a consequence of alpha-synuclein aggregation in oligodendroglia.
  • REM sleep behavior disorder
    a sleep disorder in which you physically act out vivid, often unpleasant dreams with vocal sounds and sudden, often violent arm and leg movements
  • dementia with Lewy bodies

    causes a progressive decline in mental abilities.

    It may also cause visual hallucinations, which generally take the form of objects, people or animals that aren't there. This can lead to unusual behavior such as having conversations with deceased loved ones.

    Another indicator of Lewy body dementia may be significant fluctuations in alertness and attention, which may include daytime drowsiness or periods of staring into space. And, like Parkinson's disease, Lewy body dementia can result in rigid muscles, slowed movement and tremors.

  • Pure autonomic failure
    Pure autonomic failure is dysfunction of many of the processes controlled by the autonomic nervous system, such as control of blood pressure•Blood pressure may decrease when people stand, and they may sweat less and may have eye problems, retain urine, become constipated, or lose control of bowel movements
  • Healthy controls
    Healthy normals with no neurological involvement
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: December 22, 2015)
170
Original Estimated Enrollment Same as current
Estimated Study Completion Date February 2021
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Subjects with PD, MSA and DLB that fulfill current diagnostic criteria.

  • Subjects with RBD that have polysomnography-confirmed diagnosis showing evidence of lack of muscle atonia and dream enacting behaviors during REM sleep.
  • Subjects with isolated autonomic failure (i.e., no motor deficits) that have evidence of neurogenic orthostatic hypotension and other features of autonomic failure without clinical evidence of cognitive impairment.
  • Control subjects with no history of neurological or ophthalmological disorders.

Exclusion Criteria:

  • Subjects with glaucoma, retinopathy, or significant media opacification (e.g., cataracts).
  • Subjects with a history of eye surgery or eye trauma
  • Inability to comply with the requirements of the study
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Jose M Martinez, MA 212 263 7225 jose.martinez@nyumc.org
Contact: Lucy J Norcliffe-Kaufmann, PhD. 212 263 7225 lucy.norcliffe-kaufmann@nyumc.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02640339
Other Study ID Numbers 15-01391
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party NYU Langone Health
Study Sponsor NYU Langone Health
Collaborators Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Horacio C Kaufmann, MD NYU Langone Health
PRS Account NYU Langone Health
Verification Date December 2019