Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03647137 |
| Other study ID # |
B1631-I |
| Secondary ID |
HUM00110351 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 7, 2016 |
| Est. completion date |
May 26, 2021 |
Study information
| Verified date |
March 2023 |
| Source |
VA Office of Research and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of
responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing
PD is associated with disabling axial motor complications, such as freezing of gait (FoG),
with decreased or even refractory dopamine responsiveness in over 50% of patients. The
management of dopamine resistant gait problems represents the most important unmet need in
PD. This study will related detailed motor testing to brain PET imaging to see if certain
molecules (or lack thereof) involved with neurologic transmission in the brain are involved
with FoG.
Description:
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of
responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing
PD is associated with disabling axial motor complications, such as freezing of gait (FoG),
with decreased or even refractory dopamine responsiveness in over 50% of patients. The
management of dopamine resistant gait problems represents the most important unmet need in
PD. At present, there is no biomarker of FoG in patients with PD as there is a lack of
mechanistic understanding of dopamine nonresponsiveness of FoG. The investigators have
previously identified cholinergic denervation as a prominent factor related to both falls and
gait slowing in PD. The investigators recently identified that cortical -amyloid deposition
not only associates with cognitive decline but also with postural instability and gait
difficulties in PD. In this proposal, the investigators present preliminary data suggesting
that FoG is associated with either cholinopathy, amyloidopathy or both in PD. The
investigators propose to test the novel hypothesis that comorbid amyloidopathy may be a
possible mechanistic factor underlying the poor response of FoG to dopaminergic therapy in
advancing PD. In contrast, isolated cholinopathy would be expected to be associated with
preserved dopamine responsiveness of FoG. For this purpose, the investigators propose to
perform detailed motor, including FoG, testing in PD patients "on" and "off" their
dopaminergic medications and relate this to dopaminergic 11C-dihydrotetrabenazine (DTBZ),
vesicular acetylcholine transporter 18F-fluoroethoxybenzovesamicol (FEOBV) and -amyloid
11C-labeled Pittsburgh Compound-B (PIB) brain PET imaging in PD subjects with and without
FoG. Furthermore, based on recent clinical observations that serotoninergic drugs, like the
popular anti-depressant selective serotonin reuptake inhibitor (SSRI) drugs, are associated
with significantly lower build- up of -amyloid plaques in the elderly population, and based
on the investigators' subsequent observation of an intriguing inverse relationship between
-amyloid plaque deposition and striatal serotoninergic terminal in PD, the investigators
propose to perform an exploratory sub-study to test a new hypothesis that PD subjects with
FoG will exhibit not only higher striatal -amyloid but also lower striatal serotoninergic
innervation (as determined by 11C-DASB serotonin PET imaging) compared to PD subjects without
FoG. If confirmed, positive findings in this study would allow the identification of
different PD subgroups ('personalized medicine'), such as presence amyloidopathy or
cholinopathy, to select patients for targeted pharmacotherapies to potentially prevent the
development of FoG (anti-amyloid, such as serotoninergic drugs) or manage its clinical
manifestation (cholinergic augmentation therapy) in order to preserve and maintain a good
quality of life in individuals with PD.
