Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05487300 |
| Other study ID # |
00152581 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
May 11, 2022 |
| Est. completion date |
May 1, 2023 |
Study information
| Verified date |
May 2023 |
| Source |
University of Utah |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Parkinson's disease (PD) is characterized by the gradual onset of motor symptoms such as
bradykinesia, rigidity, tremor, gait difficulties and postural instability, as well as
non-motor symptoms such as cognitive impairment and autonomic dysfunction among others.
Neurogenic orthostatic hypotension (nOH) is the main clinical manifestation of cardiovascular
autonomic dysfunction. The arterial baroreflex allows for beat-to-beat regulation of the
blood pressure and heart rate via differential modulation of its cardiovagal
(parasympathetic) and noradrenergic (sympathetic) efferent limbs. Several mechanisms may
contribute to nOH in PD including baroreflex-cardiovagal and baroreflex-sympathetic
noradrenergic failure. The prevalence of nOH in PD increases with age and disease duration;
however, several studies have documented that nOH may appear early in the course of PD and
reported prevalence of nOH in PD ranges from 30% to 65%. The presence of nOH in PD is
associated with poor outcomes related to cardiovascular events, increased morbidity and
mortality, more rapid disease progression, cognitive impairment, and falls.
Levodopa is a precursor of dopamine and is the treatment of choice to treat the motor
symptoms of 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 in different studies. As a result, clinicians may be reluctant to prescribe levodopa
in patients with PD with nOH (PD+OH), which leads to suboptimal management of motor symptoms.
On the other hand, several 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 nOH (PD-OH) by performing standardized
autonomic testing in the same patients on and off levodopa.
Clinical assessment: We will perform a medical history and physical examination before the
testing procedures (baseline visit). The baseline visit will be performed on levodopa. The
scales and assessments will include the Composite Autonomic Symptoms Score 31 (COMPASS 31),
the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating
Scale (MDS-UPDRS) part I, II, III, and Hoehn and Yahr stage. The clinical assessment and
scales are part of the standard of care in PD. Orthostatic vital signs will active standing
will be also performed the two days of autonomic testing.
Participants will undergo a baseline visit. During the baseline visit, investigators will
perform a medical history and physical examination and complete the following scales:
Composite Autonomic Symptoms Score 31 (COMPASS 31), the Movement Disorder Society-Sponsored
Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III, and
Hoehn and Yahr. Participants will undergo autonomic testing on two separate days. The first
autonomic testing will occur within 4 weeks of the baseline visit. The two autonomic tests
will occur within a 2-week timeframe. To avoid any confounding of treatment effects and
period effects, the order of testing (on versus off levodopa) will be randomized so testing
on the first day will be on-levodopa for half of the participants and off-levodopa for the
other participants. Autonomic testing will include assessment of heart rate and blood
pressures responses during the Valsalva maneuver and a 10-minute tilt table test.
