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Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy (PMPSP)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03330353
Recruitment Status : Unknown
Verified November 2017 by Shirley Wray, Massachusetts General Hospital.
Recruitment status was:  Recruiting
First Posted : November 6, 2017
Last Update Posted : November 7, 2017
Sponsor:
Collaborators:
NeurOptics Inc.
University of Toronto
Information provided by (Responsible Party):
Shirley Wray, Massachusetts General Hospital

Brief Summary:

The specific aim of this study is to investigate rod, cone and melanopsin driven pupillary light response in individuals with progressive supranuclear palsy (PSP), age-matched healthy controls and individuals with other neurodegenerative diseases using chromatic pupillometry, with special interest in assessing melanopsin-driven post-illumination pupil response (PIPR) as an identifier for PSP.

The study addresses the following hypotheses:

  1. Chromatic pupil responses, including rod/cone-driven rapid phase constriction and melanopsin-driven PIPR, are reduced in subjects with PSP compared to age-matched normal healthy control subjects,
  2. Pupil parameters of the melanopsin-driven PIPR are abnormal in PSP subjects without supranuclear palsy, which is indicative of a subclinical physiological deficit of the OPN in the early stages of PSP.

If these hypotheses are upheld, chromatic pupillometry to measure the PIPR promises to be a reliable in vivo, non-invasive, convenient and inexpensive technique to detect asymptomatic pupillomotor impairment in advance of diagnostic oculomotor signs and deterioration of cognitive function.


Condition or disease Intervention/treatment
PSP - Progressive Supranuclear Palsy PD - Parkinson's Disease AD - Alzheimer's Disease ALS (Amyotrophic Lateral Sclerosis) Diagnostic Test: Pupillometry

Detailed Description:

In 1963, Richardson, Steele and Olszewski published a landmark clinical report on 8 cases of supranuclear ophthalmoplegia, pseudobulbar palsy, nuchal dystonia and dementia and established the syndrome of heterogeneous system degeneration as a clinicopathological entity now known as PSP. The disease has a characteristic onset in the sixth decade (range 45 to 75 years) with some combination of impaired balance, abrupt falls, visual disturbances, slurred speech, dysphasia and vague changes in personality.

Slowing of voluntary vertical saccades, either down, up or both are a diagnostic marker of PSP and later impairment of voluntary horizontal saccades are characteristic in more than half of the cases. However, a proportion of PSP patients do not demonstrate these eye signs for a year or more after the onset of the disease.

This pilot study will use chromatic pupillometry to determine whether such a novel methodology may be used as an objective in vivo identifier of PSP. The rationale for the study is based in part on:

  1. Clinicopathological correlation between the key clinical signs of a supranuclear gaze palsy with pathological verification that the degenerative process affects the pretectum and rostral midbrain,
  2. The melanopsin-signaling pathway from ipRGCs (intrinsically photosensitive retinal ganglion cells) in the eye projects to the OPN (olivary pretectal nucleus) in the midbrain,
  3. Chromatic pupillometry is a non-invasive technique suitable for elderly subjects with or without dementia.

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Study Type : Observational
Estimated Enrollment : 56 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Functional Assessment of the Melanopsin-Containing Retinal Ganglion Cells in Progressive Supranuclear Palsy Using Chromatic Pupillometry
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : October 1, 2019


Group/Cohort Intervention/treatment
Neurodegenerative Diseases
Individuals with neurodegenerative diseases
Diagnostic Test: Pupillometry
Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases




Primary Outcome Measures :
  1. Maximal Pupil Constriction [ Time Frame: 2 years ]
    The smallest pupil size following light stimulation. This parameter primarily represents rapid phase extrinsic ipRGC activity driven by rods and cones through synaptic input.

  2. Post-illumination pupil response (PIPR) [ Time Frame: 2 years ]
    Measured pupil diameter over a period of 20 seconds, from 10 to 30 seconds after the offset of light stimulation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects diagnosed with PSP and age-matched control subjects
Criteria

Inclusion Criteria:

  1. Individuals that meet the clinical criteria for PSP. Core features include:

    • Recurrent falls and unsteady gait
    • Axial and nuchal rigidity
    • Pseudobulbar palsy
    • Bilateral lid retraction
    • Supranuclear vertical gaze palsy
    • Atrophy of the midbrain tegmentum (the hummingbird sign on brain MRI,
  2. Individuals that fit the criteria for the second PSP phenotype (which resembles PD) that has asymmetric findings, tremors and poor responses to treatment with Levodopa,
  3. Individuals that meet the clinical criteria for PD with:

    • Progressive bradykinesia
    • Postural instability and frequent falls
    • Festinating gait with loss of associated movements
    • Cogwheel rigidity and mask-like face
    • Rest tremor,
  4. Individuals who carry a diagnosis of Alzheimer' disease who present with progressive impairment of memory and cognitive domains such as language and visuospatial perception.

Diagnoses will be confirmed by the review of health/medical records of patients recruited from the Frontotemporal Disorders Unit clinic. In the case of participants recruited from research studies, diagnoses will be confirmed by the review of the research diagnoses indicated on the individuals' research records.

Exclusion Criteria:

  1. Individuals who are frail or in questionable health,
  2. Individuals with cataracts or with posterior pole ocular pathology such as age-related macular degeneration and optic neuropathies, including open angle high intraocular pressure glaucoma,
  3. Individuals with photophobia (i.e., painful light sensitivity) when exposed to bright light, including those with ophthalmological conditions such as keratitis (herpes simplex), uveitis or Achromatopsia,
  4. Individuals with advanced dementia with inability to sit erect, hold the eyes open, incontinence,
  5. Individuals with epilepsy,
  6. Individuals diagnosed with major depression or other severe psychiatric disorders

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): NCT03330353


Contacts
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Contact: Shirley H Wray, MD, PhD 617-726-5539 wray@helix.mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Shirley H Wray, MD, PhD, FRCP    617-726-5539    wray@helix.mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
NeurOptics Inc.
University of Toronto
Investigators
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Principal Investigator: Shirley H Wray, MD, PhD Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Shirley Wray, Massachusetts General Hospital:
Informed Consent Form  [PDF] October 20, 2017


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Responsible Party: Shirley Wray, Professor of Neurology, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03330353    
Other Study ID Numbers: 2017p001603
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: November 7, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Coded data will be shared with co-investigators

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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
Alzheimer Disease
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Supranuclear Palsy, Progressive
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dementia
Tauopathies
Neurocognitive Disorders
Mental Disorders
Paralysis
Neurologic Manifestations
Signs and Symptoms
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Eye Diseases