Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03330353
Other study ID # 2017p001603
Secondary ID
Status Recruiting
Phase N/A
First received September 19, 2017
Last updated November 3, 2017
Start date November 1, 2017
Est. completion date October 1, 2019

Study information

Verified date November 2017
Source Massachusetts General Hospital
Contact Shirley H Wray, MD, PhD
Phone 617-726-5539
Email wray@helix.mgh.harvard.edu
Is FDA regulated No
Health authority
Study type Observational

Clinical 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 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 56
Est. completion date October 1, 2019
Est. primary completion date October 1, 2019
Accepts healthy volunteers No
Gender All
Age group 55 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
Pupillometry
Use of pupillometry to assess melanopsin-light pathway in patients with neurodegenerative diseases

Locations

Country Name City State
United States Massachusetts General Hospital Boston Massachusetts

Sponsors (3)

Lead Sponsor Collaborator
Massachusetts General Hospital NeurOptics Inc., University of Toronto

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 2 years
Primary 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. 2 years
See also
  Status Clinical Trial Phase
Terminated NCT02528071 - Prognostic Value of a Diaphragmatic Endurance Test in Patients With Amyotrophic Lateral Sclerosis
Active, not recruiting NCT03604822 - Music Therapy Protocol to Support Bulbar and Respiratory Functions in ALS N/A
Completed NCT02891629 - Safety and Feasibility of the EyeControl Device N/A
Completed NCT02164253 - Focal Accumulation of Iron in Cerebral Regions in Early ALS (Amyotrophic Lateral Sclerosis) Patients Phase 2
Completed NCT00786032 - A Clinical Demonstration of EEG Brain-computer Interface for ALS Patients N/A
Recruiting NCT03787420 - Development and Needs Assessment and Efficiency of Smart Communication System for Patients With ALS. N/A
Recruiting NCT05663008 - Impairments of Neuro-muscular Communication in Motor-Neuron Disease: A Bio-Marker for Early and Personalised Diagnosis
Active, not recruiting NCT02286011 - Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis Phase 1
Active, not recruiting NCT03081338 - A Programme for Amyotrophic Lateral Sclerosis Care in Europe N/A
Active, not recruiting NCT03241784 - T-Regulatory Cells in Amyotrophic Lateral Sclerosis Phase 1
Not yet recruiting NCT04849065 - Clinical Trial on the Use of Cell Therapy in the Treatment of Patients With Amyotrophic Lateral Sclerosis Phase 2
Active, not recruiting NCT05276349 - Home-based Remote Digital Monitoring to Assess ALS Progression (Track ALS)
Completed NCT04090684 - Ciprofloxacin/Celecoxib Combination in Patients With ALS Phase 1
Active, not recruiting NCT04055623 - T-regulatory Cells in ALS Phase 2
Completed NCT02709330 - ALS Reversals - Lunasin Regimen Phase 2
Completed NCT03482050 - A Study to Evaluate Transplantation of Astrocytes Derived From Human Embryonic Stem Cells, in Patients With Amyotrophic Lateral Sclerosis (ALS) Phase 1/Phase 2