Phase 2
Completed N=30
Modulation of GABA-A Receptors in Parkinson Disease-Flumazenil Arm
Source: ClinicalTrials.gov NCT03462641 ↗Enrolled (actual)
30
Serious AEs
0.0%
Results posted
Jun 2022
Primary outcomePrimary: Postural Instability and Gait Disorder (PIGD) Score — 4.625; 4.625; 4.23; 4.09 score on a scale — p=0.0407
Summary
This arm is a positron emission tomography (PET) biomechanistic GABA-A receptor target engagement study that includes detailed clinical and motor assessments before and after the i.v. administration of 1 mg flumazenil or placebo in Parkinson disease subjects. Each subject will receive 1mg flumazenil or placebo at two visits.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Postural Instability and Gait Disorder (PIGD) Score |
4.625; 4.625; 4.23; 4.09 | 0.0407 sig |
| PRIMARY PIGD Score Change |
-1.375; -2.500 | 0.00000029 sig |
Eligibility Criteria
Inclusion Criteria
- Parkinson's disease (PD): PD diagnosis will follow the UK Parkinson's Disease Society Brain Bank Research Center (UKPDSBRC) clinical diagnostic criteria for PD.
- Hoehn and Yahr stages 2-4
- Absence of dementia confirmed by cognitive testing.
- Abnormal 11C-Dihydrotetrabenazine ([11C]-DTBZ) PET study to demonstrate nigrostriatal dopaminergic denervation.
Exclusion Criteria
- PD with Dementia (PDD) or dementia with Lewy bodies (DLB).
- Other disorders which may resemble PD, such as vascular dementia, normal pressure hydrocephalus, multiple system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism. Prototypical cases have distinctive clinical profiles, like early and severe dysautonomia or appendicular apraxia, which may differentiate them from idiopathic PD. The use of the UKPDSBRC clinical diagnostic criteria for PD will mitigate the inclusion of subjects with atypical parkinsonism.
- Subjects on benzodiazepine, GABA-ergic medications (baclofen, tizanidine), neuroleptic, anticholinergic (trihexyphenidyl, benztropine), or cholinesterase inhibitor drugs.
- Evidence of a mass lesion on structural brain imaging (MRI).
- Participants in whom MRI is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, chest, or cochlear implant.
- Severe claustrophobia precluding MR or PET imaging.
- Subjects limited by participation in research procedures involving ionizing radiation.
- Pregnancy (urine or serum pregnancy test within 48 hours of each PET session) or breastfeeding.
- History of seizures
- Significant anxiety or history of panic disorder.
- History of recent suicide attempt or overdose of tricyclic antidepressants or other medications
- Any other medical history determined by investigators to preclude safe participation.
- Allergy to flumazenil
- Significant liver disease
- History of alcohol or other substance abuse within past two years.
- History of regular benzodiazepine use within past year
Data sourced from ClinicalTrials.gov (NCT03462641). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.