PSP - Progressive Supranuclear PalsyPMPSPNCT03330353
Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy
An observational study of PSP - Progressive Supranuclear Palsy and PD - Parkinson's Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- PSP - Progressive Supranuclear Palsy, PD - Parkinson's Disease, AD - Alzheimer's Disease
- What is being tested?
- Pupillometry
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 1 Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects diagnosed with PSP and age-matched control subjects
Who may be able to join
- 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
Show all 16Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Shirley H Wray, MD, PhD, FRCP, 617-726-5539, wray@helix.mgh.harvard.edu
About this study
Official title: 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:
Read more
- 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.
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:
- 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.
- Conditions
- PSP - Progressive Supranuclear Palsy, PD - Parkinson's Disease, AD - Alzheimer's Disease, ALS (Amyotrophic Lateral Sclerosis)
- Being tested
- Pupillometry
- Medical subject headings
- Supranuclear Palsy, Progressive, Parkinson Disease, Alzheimer Disease, Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PupillometryDiagnostic test
Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases
| Study group | Role | What they receive |
|---|---|---|
| Neurodegenerative Diseases | Individuals with neurodegenerative diseases Receives: Diagnostic Test: Pupillometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Nov 2017
- Primary completion1 Oct 2019 (estimated)
- Study completion1 Oct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PSP - Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- NeurOptics Inc, University of Toronto
- Responsible party
- Principal investigator, Shirley Wray, Massachusetts General Hospital
- Investigators
- Shirley H Wray, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03330353
- Sponsor's protocol ID
- 2017p001603
- Acronym
- PMPSP
- Status last verified
- Nov 2017
- First submitted
- 19 Sep 2017
- Last updated
- 7 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Coded data will be shared with co-investigators
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Assessment of the Melanopsin-Containing Retinal Ganglion Cells in Progressive Supranuclear Palsy Using Chromatic Pupillometry
- ClinicalTrials.gov ID
- NCT03330353
- Acronym / sponsor ID
- PMPSP / 2017p001603
- Conditions
- PSP - Progressive Supranuclear Palsy, PD - Parkinson's Disease, AD - Alzheimer's Disease, ALS (Amyotrophic Lateral Sclerosis)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- NeurOptics Inc, University of Toronto
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 1 Oct 2019 (estimated)
- Study completion
- 1 Oct 2019 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neurodegenerative Diseases | – | Diagnostic Test: PupillometryIndividuals with neurodegenerative diseases |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects diagnosed with PSP and age-matched control subjects
Key inclusion criteria (16 listed)
- Individuals that meet the clinical criteria for PSP. Core features include:
- 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:
- 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.
Key exclusion criteria (6 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PupillometryUse of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases | Diagnostic test | Neurodegenerative Diseases |
Primary outcome
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2017.
- Individual participant dataSharing planned: No. Coded data will be shared with co-investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley H Wray, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PSP - Progressive Supranuclear Palsy and PD - Parkinson's Disease, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shirley H Wray, MD, PhD (617-726-5539, wray@helix.mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Pupil Constriction (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2017.