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

November 3, 2017 updated by: Shirley Wray, Massachusetts General Hospital

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:

  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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

51 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects diagnosed with PSP and age-matched control subjects

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Neurodegenerative Diseases
Individuals with neurodegenerative diseases
Diagnostic test: Pupillometry
Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Toronto
NeurOptics Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Shirley H Wray, MD, PhD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017p001603

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Coded data will be shared with co-investigators

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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