Effect of Levodopa on Cardiovascular Autonomic Function in Parkinson's Disease

NCT05487300 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 00152581
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Levodopa is a precursor of dopamine and is the treatment of choice to treat the motor symptoms of Parkinson's disease (PD); however, the effect of levodopa on cardiovascular autonomic function in PD is poorly understood. Orthostatic hypotension has been documented as a potential side effect of levodopa. As a result, clinicians may be reluctant to prescribe levodopa in patients with PD with neurogenic orthostatic hypotension (PD+OH), which leads to suboptimal management of motor symptoms. On the other hand, other studies failed to show any clear relationship between levodopa and orthostatic hypotension in patients with PD. Important limitations of prior studies include the lack of detailed investigation of baroreflex cardiovagal and sympathetic noradrenergic functions and the fact that the same patients were not tested on and off levodopa. The investigators propose to investigate the effects of levodopa on cardiovascular autonomic function in patients with PD+OH and PD without neurogenic orthostatic hypotension (PD-OH) by performing standardized autonomic testing in the same patients on and off levodopa.

Conditions

Parkinson Disease; Orthostatic Hypotension

Outcome Measures

Primary Outcomes (1)

• Change in Systolic Blood Pressure From Supine to Tilt at 3 Minutes

  Change in systolic blood pressure from supine to tilt at 3 minutes

  from supine (baseline) to tilt at 3 minutes

Secondary Outcomes (2)

• Baroreflex Cardiovagal Function

  Measure during Valsalva maneuver during autonomic testing (on levodopa and off levodopa)

• Baroreflex Adrenergic Sensitivity

  BRS-A was calculated during the Valsalva maneuver (on and off levodopa)

Study Arms (2)

Testing on-levodopa first, then off-levodopa

OTHER

Participants underwent autonomic testing one hour after taking their regular morning dose of levodopa (ON state). On a separate day, they then underwent autonomic testing after at least 12 hours from the last dose of levodopa (OFF state).

Drug: Autonomic testing on and off levodopa

Testing off-levodopa, then on-levodopa

OTHER

Participants underwent autonomic testing after at least 12 hours from the last dose of levodopa (OFF state). On a separate day, they then underwent autonomic testing one hour after taking their regular morning dose of levodopa (ON state).

Drug: Autonomic testing on and off levodopa

Interventions

Autonomic testing on and off levodopa DRUG

Participants with Parkinson's disease with and without orthostatic hypotension will undergo standardized autonomic testing on two separate days "on levodopa" and "off levodopa".

Testing off-levodopa, then on-levodopa; Testing on-levodopa first, then off-levodopa

Eligibility Criteria

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

You may qualify if:

• Subjects with a diagnosis of Parkinson's disease
• For the subgroup of participants with orthostatic hypotension (OH), OH will be defined by a sustained drop in systolic blood pressure \> 20 mmHg and/or a drop in diastolic blood pressure \> 10 mmHg within 3 minutes from supine to standing during tilt not attributable to medications. Autonomic testing and a ratio of orthostatic heart rate change/systolic blood pressure change \< 0.5 bpm/mmHg will confirm the neurogenic etiology.

You may not qualify if:

• Any medication indicated for withdrawal that would result in undue risk to the participant if discontinued or that would confound heart rate and blood pressure measures
• Cognitive impairment that limits the ability to follow instructions

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Hypotension, Orthostatic

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

Results Point of Contact

• Title: Dr. Guillaume Lamotte
• Organization: University of Utah

guillaume.lamotte@hsc.utah.edu

801-585-7575

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 29, 2022
• First Posted: August 4, 2022
• Study Start: May 11, 2022
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (1)