Relationship Between Symptoms, Retinal Morphology, and the Nigrostriatal Dopamine System in Parkinson's Disease

Relationship Between Symptom Severity, Retinal Morphology, and the Nigrostriatal Dopamine System in the Brain in Parkinson's Disease

The purpose of this study is to examine if a correlation exists between findings from brain imaging studies of the status of the dopamine system in the brain using DaTscan and SPECT imaging, clinical symptoms of Parkinson's disease, and changes in the structure of the retina as detected by optical coherence tomography (OCT) in recently diagnosed and more advanced Parkinson's disease patients.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will be Parkinson's disease patients (Hoehn and Yahr stage 1 - 3). One study group will be subjects (N = 6) with early PD who will be within 3 years from diagnosis and not requiring dopaminergic therapy. These subjects will need to have Unified Parkinson's Disease Rating Scale motor scores of 10 - 15. The second study group will be subjects (N = 6) with more advanced PD and will have had PD for at least 5 years and will need to have Unified Parkinson's Disease Rating Scale motor scores of > 20.

Description

Inclusion Criteria:

1. Willing and able to give informed consent.
2. Between the ages of 50-80 years old.
3. Male or female with idiopathic PD who fulfill UK PD Society brain bank criteria for diagnosis of Parkinson's disease.
4. Early stage subjects will need to have Unified Parkinson's Disease Rating Scale (UPDRS) motor scores of < 10, be within 3 years of diagnosis, and not requiring dopaminergic therapy
5. Later stage subjects will need to have Unified Parkinson's Disease Rating Scale motor scores of > 20 and be > 5 years from diagnosis

6. If female, one of the following three scenarios must apply:

   • at least two years post-menopausal
   • surgically sterile
   • negative urine pregnancy test, and following a reliable method of birth control (oral contraceptive, intrauterine device, contraceptive implant, barrier, or abstinence) for at least two months prior to entry, and agreeing both to follow a reliable method of birth control, and (if relevant) to desist from breast feeding during, and for two weeks following tracer administration.

Exclusion Criteria:

1. Abrupt onset of Parkinsonism
2. 'Other Parkinson-like syndromes (e.g. progressive supranuclear palsy, multiple system atrophy)
3. Any condition that would preclude successful completion of SPECT scanning
4. Use of anti-coagulant therapy
5. Any clinically significant eye disease that would complicate interpretation of OCT data
6. Use of any drugs that would alter or interfere with tracer binding for SPECT imaging studies (ex., cocaine, amphetamines, methylphenidate, ephedrine, phentermine, bupropion, fentanyl, selective serotonin reuptake inhibitors).
7. Known sensitivity to the imaging agent or to Lugol's solution or to potassium perchlorate.
8. History or presence of severe renal disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Early Parkinson's disease patients; All subjects will undergo a complete neuro-ophthalmological examination, including assessment of best-corrected visual acuity, ocular motility, pupillary reflexes, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and dilated fundus examination, followed by an optical coherence tomography study. Subjects will also have a DaTscan for striatal dopamine transporter visualization using single photon emission computed tomography (SPECT) brain imaging. A clinical examination will also be performed in order to document motor and cognitive functioning.
Advanced Parkinson's disease patients; All subjects will undergo a complete neuro-ophthalmological examination, including assessment of best-corrected visual acuity, ocular motility, pupillary reflexes, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and dilated fundus examination, followed by an optical coherence tomography study. Subjects will also have a DaTscan for striatal dopamine transporter visualization using single photon emission computed tomography (SPECT) brain imaging. A clinical examination will also be performed in order to document motor and cognitive functioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OCT results	OCT measures including measurements of the thickness (microns) of specific retinal layers including RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, photoreceptors, and retinal pigment epithelium.	1 day
DaTscan results	Striatal binding ratios will be calculated for striatal regions of interest.	1 day
Clinical examination results	UPDRS motor score	1 day

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Wills Eye Hospital
• Investigators: Principal Investigator: Jay S Schneider, PhD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 13, 2015
• First Posted (Estimate): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 11, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 15D.060

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No