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Status unknownNCT03330353PMPSPUpdated Nov 7, 2017

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

An observational study in PSP - Progressive Supranuclear Palsy, PD - Parkinson's Disease and AD - Alzheimer's Disease, sponsored by Massachusetts General Hospital. Status unknown at 1 site in United States. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2017-11-07.

Sponsored by Massachusetts General Hospital · Observational

The sponsor has not verified this record recently (last verified Nov 2017), so the status shown — last known as Recruiting — may be out of date.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
56
Ages
55 Years and older
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • PSP - Progressive Supranuclear Palsy
  • PD - Parkinson's Disease
  • AD - Alzheimer's Disease
  • ALS (Amyotrophic Lateral Sclerosis)
03

In context

Supranuclear Palsy, Progressive

166 studies on the registry are indexed under Supranuclear Palsy, Progressive; 49 are open to participants now.

This study's planned enrollment of 56 is below the median of 200 across 64 observational studies indexed under Supranuclear Palsy, Progressive.

Browse Supranuclear Palsy, Progressive studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,582 studies on the registry; 451 are open to participants now.

Of its 221 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.

Browse Massachusetts General Hospital studies →

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Subjects diagnosed with PSP and age-matched control subjects

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
56 participants (estimated)
Patient registry
No

Groups and cohorts

  • Neurodegenerative Diseases

    Individuals with neurodegenerative diseases

    Diagnostic Test: Pupillometry

Interventions

  • Diagnostic testPupillometry

    Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases

06

What researchers measure

Primary outcomes

  1. Maximal Pupil Constriction

    The smallest pupil size following light stimulation. This parameter primarily represents rapid phase extrinsic ipRGC activity driven by rods and cones through synaptic input.

    Time frame: 2 years

  2. Post-illumination pupil response (PIPR)

    Measured pupil diameter over a period of 20 seconds, from 10 to 30 seconds after the offset of light stimulation.

    Time frame: 2 years

07

Study locations

1 of 1 sites recruiting
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
    Recruiting
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 18, 2017
  • Informed consent form · Oct 20, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Coded data will be shared with co-investigators

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Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Nov 2017 (actual). Primary completion is estimated for Oct 2019, 23 months after the start.

Of 37 observational studies under Supranuclear Palsy, Progressive, half reached primary completion within 81 months of starting (the median), counting those still running; a quarter within 54. This study's planned 23 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 19, 2017
First posted
Nov 6, 2017
StartActual
Nov 1, 2017
Primary completionEst.
Oct 1, 2019
CompletionEst.
Oct 1, 2019
Last update
Nov 7, 2017
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Nov 7, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03330353
Lead sponsor
Massachusetts General Hospital
Collaborators
NeurOptics Inc, University of Toronto
Responsible party
Shirley Wray (Professor of Neurology, Harvard Medical School, Massachusetts General Hospital) — Principal investigator
First posted
Nov 6, 2017
Start date
Nov 1, 2017
Primary completion
Oct 1, 2019 (estimated)
Completion
Oct 1, 2019 (estimated)
Last update
Nov 7, 2017

Study contacts

Shirley H Wray, MD, PhD
Contact
wray@helix.mgh.harvard.edu
617-726-5539
Shirley H Wray, MD, PhD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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