The Role of the Noradrenergic System in the Nonmotor Symptoms of Parkinson's Disease

NCT04346394 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: D19090
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn about the role of noradrenergic system in the non-motor symptoms of Parkinson's disease. The main objectives it aims to answer are:

• Discussing and signing the Informed Consent Form
• Discussing Medical History and Current Medications
• Collecting Blood samples
• Measuring heart rate and blood pressure
• Mental health screening and neurocognitive questionnaires
• Pupil test
• Test to feel vibrations Visit two will consist of :
• Mental Health questionnaire
• IV Placement
• Blood Draws
• Administration of Yohimbine hydrochloride
• Head up tilt table
• Measuring heart rate and blood pressure
• Answering questions about anxiety, mood, and fatigue using a scale
• Pupil tests Visit three will be a follow-up call from the Nurse Coordinator to discuss any adverse events.

Conditions

Parkinson Disease

Keywords

Parkinson's; Orthostatic Hypotension; Yohimbine

Outcome Measures

Primary Outcomes (1)

• Difference in fatigue (measured with the self-reported Fatigue Severity Scale) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH)

  The Fatigue Severity Scale (FSS) measures average fatigue experienced over the previous week. The FSS questionnaire contains nine statements that rate the severity of fatigue symptoms. A low value indicates strong disagreement with the statement, a high value indicates strong agreement. A total score of 36 or more suggests presence of fatigue.

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

Secondary Outcomes (9)

• Difference in apathy (measured with the self-reported Apathy Evaluation Scale) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH)

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

• Difference in self-reported depression (measured with the Geriatric Depression Scale - short form) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH)

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

• Difference in self-reported anxiety (measured with the Geriatric Anxiety Inventory) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH)

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

• Difference in neurocognition (measured with average composite z-score on a neurocognitive battery) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH)

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

• Difference in informant-reported anxiety (measured by an informant-reported Neuropsychiatric Inventory Questionnaire) in patients with Parkinson's disease with and without orthostatic hypotension (PD+OH v PD-OH).

  All measurements for this study will be obtained during one of the two study visits that each subject will undergo. These two visits will be completed within 6 months of subject enrollment

Other Outcomes (6)

• Between group (Parkinson patients with and without orthostatic hypotension (PD+OH v PD-OH) change in self-reported anxiety before and after yohimbine administration

  Baseline and 45 minutes after yohimbine administration

• Between group (Parkinson patients with and without orthostatic hypotension (PD+OH v PD-OH) change in self-reported mood before and after yohimbine administration

  Baseline and 45 minutes after yohimbine administration

• Between group (Parkinson patients with and without orthostatic hypotension (PD+OH v PD-OH) change in self-reported fatigue before and after yohimbine administration

  Baseline and 45 minutes after yohimbine administration

Study Arms (1)

Yohimbine

EXPERIMENTAL

The first visit in the study has no interventional drug. Yohimbine (5mg) is administered orally during visit two, during a head up tilt test, to manipulate the noradrenergic system to determine the association between OH and NP symptoms in those with PD. Yohimbine is not administered as a treatment in this study, but as a pharmacologic tool to study the adrenergic system.

Drug: Yohimbine HCl

Interventions

Yohimbine HCl DRUG

Yohimbine hydrochloride will be used to manipulate the noradrenergic system during some of the assessments. By measuring the amounts of hormones the body produces before and after yohimbine hydrochloride administration, researchers can assess how well the noradrenergic system is functioning

Also known as: Yohimbine hydrochloride, yohimbine

Yohimbine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant able to provide informed consent
• Diagnosis of Parkinson's disease confirmed by a DH neurologist according to Movement Disorder Society criteria, with the exception that "Red flag" 5a will not be used (severe autonomic failure within five years of disease onset).
• All subjects must have CMP and CBC drawn within 6 months of study visit 1, with results in the normal range or with abnormal results not considered to be clinically significant in the investigator's opinion.
• Female patients must be post-menopausal (at least one year) or not planning to get pregnant and have negative pregnancy test.

You may not qualify if:

• Diagnosis or previous history of diabetes of any kind
• Known autonomic neuropathy unrelated to PD
• History of or current cardiac, liver or renal disease that, in the opinion of the investigator, may put the patient at risk because of participation in the study
• Known condition that in the investigator's opinion would be a contraindication to HUT testing or yohimbine challenge (e.g. decompensated cardiac disease, severe positional vertigo; severe anxiety, known panic disorder69)
• Current use of catecholaminergic medications (e.g. stimulants, droxidopa, midodrine) that cannot be held for at least three half-lives
• Inability to hold PD medications for at least 12 hours
• History of major depressive or bipolar disorder preceding the diagnosis of PD,69 or diagnosis or previous history of psychiatric illness that in the investigator's opinion would affect the subject's ability to successfully participate in the study.
• Any history (other than PD) that could significantly and adversely affect neurocognitive function, such as history of traumatic brain injury (head injury with loss of consciousness \> 1 hour), known dementia unrelated to Parkinson's or related diseases; developmental delay, multiple sclerosis or epilepsy with cognitive impairment, intellectual deficit, diagnosed and untreated sleep apnea; untreated syphilis; HIV with HAND; or other conditions that, based on the investigators opinion, could interfere with neurocognitive evaluation.
• Known ophthalmologic disease such as untreated cataract, glaucoma, optic neuritis, orbital trauma, or other neuroretinal disease that might impact pupillary function
• Severe illness within 30 days prior to enrollment.
• Use of opiate, procholinergic, or other medications influencing pupillary function that cannot be held for three half-lives
• In the Investigator's opinion, subject would be unable to successfully participate in the study for any reason.

Sponsors & Collaborators

• Nathaniel M. Robbins: lead

Study Sites (1)

Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Hypotension, Orthostatic

Interventions

Yohimbine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Nathaniel M Robbins, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician, Assistant Professor of Neurology

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: April 15, 2020
• Study Start: May 11, 2021
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 23, 2023

Record last verified: 2023-08

Locations

US (1)