- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03330353
Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy (PMPSP)
Functional Assessment of the Melanopsin-Containing Retinal Ganglion Cells in Progressive Supranuclear Palsy Using Chromatic Pupillometry
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:
- 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,
- 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.
Study Overview
Status
Conditions
Intervention / Treatment
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:
- 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,
- The melanopsin-signaling pathway from ipRGCs (intrinsically photosensitive retinal ganglion cells) in the eye projects to the OPN (olivary pretectal nucleus) in the midbrain,
- Chromatic pupillometry is a non-invasive technique suitable for elderly subjects with or without dementia.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Shirley H Wray, MD, PhD
- Phone Number: 617-726-5539
- Email: wray@helix.mgh.harvard.edu
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114
- Recruiting
- Massachusetts General Hospital
-
Contact:
- Shirley H Wray, MD, PhD, FRCP
- Phone Number: 617-726-5539
- Email: wray@helix.mgh.harvard.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
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,
- 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,
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,
- 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:
- Individuals who are frail or in questionable health,
- 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,
- 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,
- Individuals with advanced dementia with inability to sit erect, hold the eyes open, incontinence,
- Individuals with epilepsy,
- Individuals diagnosed with major depression or other severe psychiatric disorders
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Neurodegenerative Diseases
Individuals with neurodegenerative diseases
|
Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 years
|
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.
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Shirley H Wray, MD, PhD, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Eye Diseases
- Neurologic Manifestations
- Neurocognitive Disorders
- Neuromuscular Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Dementia
- Tauopathies
- Cranial Nerve Diseases
- Ocular Motility Disorders
- Paralysis
- Ophthalmoplegia
- Parkinson Disease
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- Alzheimer Disease
- Supranuclear Palsy, Progressive
Other Study ID Numbers
- 2017p001603
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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