Airway Protective Mechanisms in PD (R01)

NCT ID: NCT03321019

Last Updated: 2024-10-10

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

119 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-12-12

Study Completion Date

2023-09-29

Brief Summary

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This study will collect data on various aspects of airway sensation and function, and determine how it relates to the development of swallowing and cough dysfunction in Parkinson's disease. Participants will be followed over a 3-year period, with once-per-year visits to collect the data.

Detailed Description

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Aspiration pneumonia (APn) occurs at a disproportionately hig rate in patients with Parkinson's disease (PD) versus healthy age-matched older adults. This is of particular public health concern given that aspiration pneumonia infection is a leading cause of death in persons with PD. The development of APn is multifactorial with aspiration of material from disordered swallowing (dysphagia) without proper cough response being the main contributing factor. These findings reflect the fact that both swallowing and cough are sensorimotor behaviors, and thus require appropriate detection and scaling of a sensory stimulus in order to produce an appropriate motor response.

The long-term goal of this research is to advance the management of airway protection deficits in patients with neurodegenerative disease in order to decrease morbidity and mortality due to aspiration related lung infection. The objective here, which is a critical step in pursuit of that goal, is to further specify the sensory mechanisms associated with airway protection disorders in order to advance the clinical management of these patients. In order to accomplish the objective of this application the study team has identified 3 aims: First, determine relationship(s) between airway somatosensation, reflex cough and swallowing function in people with PD, and how these relationships may change with disease progression, over time. Second, determine whether cortical processing of sensory information is associated with deficits in reflex cough sensitivity or swallowing function in people with PD, and third, to determine how the central neural filtering of airway sensory stimuli may relate to the development of airway protective disorders.

The study team will accomplish these aims in 2 experimental studies. First, the study team will test the magnitude of respiratory resistive loads, in people with PD across a range of disease durations, and in a healthy control group. The study team will measure reflex cough, using a cough-inducing irritant (capsaicin), and swallowing function. The study team will perform these tests at 3 time-points, spaced 10-14 months apart, in order to determine the relationships between respiratory sensation, cough sensitivity and effectiveness, and swallowing function, and how they change with advancing disease duration.

Next the study team will perform electroencephalographic recordings time-locked to paired respiratory stimuli to determine cortical processing of airway sensory information. The study team will measure the amplitude and latency of the sensory evoked potential peaks, and compute ratios of peak amplitude between the first and second paired stimulus in order to determine the degree of sensory gating. The realization of the proposed aims and studies is significant because it is a necessary step in our program of research that is expected to lead to earlier, more accurate identification, as well as targeted interventions for airway protection deficits in PD.

Completion of this research is systematically important for our goal of maintaining adequate airway protective function in PD patients; the results are expected to directly impact reductions in health care costs, morbidity, and mortality related to airway protection deficits.

Conditions

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Parkinson Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Healthy controls

Men and women between the ages of 45 and 85 years without Parkinson's disease, or any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.

Capsaicin

Intervention Type DRUG

Participants will inhale aerosolized capsaicin with the goal of this inducing cough and an urge-to-cough.

Resistive respiratory loads

Intervention Type DEVICE

Participants will breath through a mouthpiece. Every 3-5 breaths in, a respiratory load will be applied. Participants will be asked to rate the magnitude of the load.

Event-related evoked potential using electroencephalography (EEG).

Intervention Type OTHER

The study team will use EEG time-locked to a respiratory occlusion to measure the brain's response to respiratory sensation.

Fluoroscopic swallow evaluation

Intervention Type PROCEDURE

Participants will swallow various consistencies of barium under fluoroscopy (moving-picture x-ray) in order to assess swallowing safety and efficiency.

Parkinson's disease

Men and women between the ages of 45 and 85 years with Parkinson's disease, and without any history of neurologic disorder/disease, head or neck cancer, or chronic respiratory illness.

Capsaicin

Intervention Type DRUG

Participants will inhale aerosolized capsaicin with the goal of this inducing cough and an urge-to-cough.

Resistive respiratory loads

Intervention Type DEVICE

Participants will breath through a mouthpiece. Every 3-5 breaths in, a respiratory load will be applied. Participants will be asked to rate the magnitude of the load.

Event-related evoked potential using electroencephalography (EEG).

Intervention Type OTHER

The study team will use EEG time-locked to a respiratory occlusion to measure the brain's response to respiratory sensation.

Fluoroscopic swallow evaluation

Intervention Type PROCEDURE

Participants will swallow various consistencies of barium under fluoroscopy (moving-picture x-ray) in order to assess swallowing safety and efficiency.

Interventions

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Capsaicin

Participants will inhale aerosolized capsaicin with the goal of this inducing cough and an urge-to-cough.

Intervention Type DRUG

Resistive respiratory loads

Participants will breath through a mouthpiece. Every 3-5 breaths in, a respiratory load will be applied. Participants will be asked to rate the magnitude of the load.

Intervention Type DEVICE

Event-related evoked potential using electroencephalography (EEG).

The study team will use EEG time-locked to a respiratory occlusion to measure the brain's response to respiratory sensation.

Intervention Type OTHER

Fluoroscopic swallow evaluation

Participants will swallow various consistencies of barium under fluoroscopy (moving-picture x-ray) in order to assess swallowing safety and efficiency.

Intervention Type PROCEDURE

Other Intervention Names

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ERP RREP Modified barium swallow

Eligibility Criteria

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Inclusion Criteria

1. Between the ages of 45 and 85 years
2. Diagnosis of PD, Hoehn and Yahr stages I - IV, by a fellowship trained neurologist arriving at the diagnosis of PD by applying strict UK brain bank criteria (PD participants only)

Exclusion Criteria

1. Neurological disorders other than PD (i.e., stroke, etc.)
2. Difficulty complying due to neuropsychological dysfunction (i.e., severe depression)
3. Allergy to capsaicin or hot peppers
4. History of head or neck cancer
5. History of smoking in the past 5 years
6. Any neurological disorder including PD (Healthy control group only)
Minimum Eligible Age

45 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karen Hegland, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

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University of Florida Center for Movement Disorders and Neurorestoration

Gainesville, Florida, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: ICF2_longitudinal

View Document

Document Type: Informed Consent Form: longitudinal study

View Document

Other Identifiers

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5R01HD091658-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB201700959-N

Identifier Type: -

Identifier Source: org_study_id

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