Biomarkers in Neural Disorders
1 other identifier
observational
54
1 country
1
Brief Summary
This study seeks to establish the sensitivity and specificity of what appears to be a unique brainstem biomarker of Parkinson's Disease (PD) - an electrically induced olygosynaptic nasotrigeminal reflex response - in differentiating early stage PD from normal controls and from patients with various other neurodegenerative diseases. This study will additionally compare the biomarker to olfactory testing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Jun 2016
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 18, 2016
CompletedFirst Posted
Study publicly available on registry
May 4, 2016
CompletedStudy Start
First participant enrolled
June 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 16, 2019
CompletedJuly 18, 2019
July 1, 2019
2 years
April 18, 2016
July 16, 2019
Conditions
Outcome Measures
Primary Outcomes (4)
Latency, amplitude, and area under the curve of brainstem reflex response
Latency, amplitude, and area under the curve of electrical brainstem reflex response of trigeminal nerve branches measured on the face musculature (before and after short-term visual deprivation).
1 Hour
Score on the University of Pennsylvania Smell Identification Test
The number of correct odor identification responses out of 40 from the standardized University of Pennsylvania Smell Identification Test (before and after short-term visual deprivation).
20 Minutes
Score on the Odor Discrimination/Memory Test
The number of correct responses in picking out an odor previously presented from three foils 10, 30, and 60 sec later using the standardized Odor Detection/Discrimination Test (before and after short-term visual deprivation).
30 Minutes
Score on an Odor Detection Threshold Test
The average of 7 reversals in a staircase odor detection threshold test that employs phenyl ethyl alcohol (rose oil) concentrations ranging from -7 to -2 log dilutions in light mineral oil.
20 Minutes
Study Arms (11)
Parkinson's Disease
Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
Alzheimer's Disease
Non-smokers, ages 18-80, diagnosed with Alzheimer's Disease. Must meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
Progressive Supranuclear Palsy
Non-smokers, ages 18-80, diagnosed with Progressive Supranuclear Palsy. Must meet the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
Essential Tremor
Non-smokers, ages 18-80, diagnosed with Essential Tremor.
Drug-Induced Parkinson's Disease
Non-smokers, ages 18-80, diagnosed with Drug-Induced Parkinson's Disease.
Myasthenia Gravis
Non-smokers, ages 18-80, diagnosed with Myasthenia Gravis.
Multiple System Atrophy
Non-smokers, ages 18-80, who have been diagnosed with Multiple System Atrophy.
Diffuse Lewy Body Disease
Non-smokers, ages 18-80, diagnosed with Diffuse Lewy Body Disease. Must meet the Consensus Criteria for the clinical diagnosis of DLBD.
Healthy Controls
Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.
Spinal Cord Injury
Asymptomatic Relatives
Interventions
Eye blink responses will be induced using standard stimulating electrodes employed in surface electromyography (EMG). The subjects will recline with their eyes gently closed. Sticky electrodes will be placed to the left and below the left eye. 6 different facial regions will be stimulated. The electrical stimulation will be kept constant during the test sessions. To prevent habituation, the stimuli will be delivered randomly at intervals of 45-60 sec. Four 0.2 msec pulses will be presented. In some cases, paired pulse stimulation will be performed, and a conditioning stimulus will be applied to the target facial regions at the following intervals: 10, 200, 400, 600 and 800 msec. 4 pulses will be presented at each stimulus interval with randomized interval and pulse sequences.
Olfactory testing will be performed using standard tests. The University of Pennsylvania Smell Identification Test (UPSIT) assesses a subjects ability to identify odors in a forced choice format. The Snap and Sniff Threshold Test provides a threshold measure of phenyl ethyl alcohol. Short-term odor memory will be assessed using a standardized 12-item four-alternative forced-choice Odor Memory Test. This non-lexical test employs 10-, 30-, and 60-second delay intervals between the presentation of the target odorant and the first of four successively presented odors from which the target is to be selected.
During a 2-hour visual deprivation period, subjects will wear comfortable light-tight goggles with lenses that have been blackened by flat black paint. Subjects will be given the opportunity to recline comfortable in a padded reclining chair during this time.
Electrical stimulation will be applied to a nerve of your arm. Sticky electrode pads will also be placed on a hand muscle. You will receive electrical stimulations that lasts less than a second. The stimulations will make your muscle twitch.
Eligibility Criteria
Normal controls and patients with such neural disorders as Parkinson's Disease(PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP), essential tremor (ET), dementia with Parkinson's disease (D-PD), myasthenia gravis (MG), multiple system atrophy (MSA), diffuse Lewy body disease (DLBD), and Spinal Cord Injury (SCI). None will be cigarette smokers. The patients will be diagnosed accord to current consensus criteria. The healthy controls will be matched to the PD patients on such variables as sex, age, education level, and ethnicity. The Healthy Controls will be asked to answer questions regarding the disease state of their first degree family members to ensure that these first degree family members do not have a neurodegenerative diseases. Every effort will be made to include women and minority subjects.
You may qualify if:
- The Parkinson's disease (PD) patients will be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.
- The Alzheimer's disease (AD) patients will meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.
- The progressive supranuclear palsy (PSP) patients will have met the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.
- The DLBD patients will meet the Consensus Criteria for the clinical diagnosis of DLBD.
- The healthy controls will be matched to the PD patients on such variables as sex, age, education level, and ethnicity.
- The essential tremor (ET), multiple system atrophy (MSA), myasthenia gravis (MG), multiple system atrophy (MSA), Parkinson's disease dementia (D-PD), and Spinal Cord Injury (SCI) patients will meet the generally-accepted diagnostic criteria for these disorders.
You may not qualify if:
- Drug abuse.
- Any other known and potentially confounding condition that could reasonably be expected to interfere with the study assessments.
- Under age 18.
- Over age 80.
- Smoker.
- Pregnant or nursing.
- Healthy control with a first degree relative who has a neurodegenerative disease.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard L Doty, PhD
University of Pennsylvania
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 18, 2016
First Posted
May 4, 2016
Study Start
June 1, 2016
Primary Completion
June 1, 2018
Study Completion
July 16, 2019
Last Updated
July 18, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will not share