NCT03462641

Modulation of GABA-A Receptors in Parkinson Disease-Flumazenil Arm

Completed Phase 1, PHASE2 Results posted Last updated 27 September 2022

What this trial tests

Phase 1, PHASE2 trial testing Flumazenil in Parkinson Disease in 36 participants. Completed in 4 June 2021.

Timeline

9 March 2018

Primary endpoint
4 June 2021

4 June 2021

Quick facts

Lead sponsor	University of Michigan
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	other
Enrollment	36
Start date	9 March 2018
Primary completion	4 June 2021
Estimated completion	4 June 2021
Sites	1 location across United States

Drugs / interventions tested

• Flumazenil (FLUMAZENIL) — full drug profile →
• Placebo

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

University of Michigan

Who can join

Adults 50 to 99, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Postural Instability and Gait Disorder (PIGD) Score Primary · up to 3 hours (including pre and post infusion motor evaluation)

Postural Instability and Gait Disorder (PIGD) score is a subscale score of MDS-UPDRS scale. It is computed as a sum of following MDS-UPDRS items: 3.10 Gait 3.11 Freezing of gait 3.12 Postural stability 3.13 Posture Minimal possible score is 0, maximal possible score is 16. Higher scores indicate greater severity of PIGD symptoms (worse outcome).

Before Infusion

Group	Value	95% CI
Placebo	4.625	± 2.36
Flumazenil	4.625	± 2.34

After Infusion

Group	Value	95% CI
Placebo	4.23	± 2.15
Flumazenil	4.09	± 2.00

PIGD Score Change Primary · up to 3 hours (including pre and post infusion motor evaluation)

Difference in PIGD score from pre-infusion to post-infusion. Only observations where PIGD score change is less than 0 (decrease) are retained, as the hypothesis we are interested is whether the effect magnitude of flumazenil on PIGD score depends on baseline GABA-A receptor binding as assesed by FMZ PET.

Group	Value	95% CI
Placebo Responders	-1.375	± 0.5175492
Flumazenil Responders	-2.500	± 1.5165751

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Arbutin effectively ameliorates the symptoms of Parkinson's disease: the role of adenosine receptors and cyclic adenosine monophosphate.
   Zhao J, Kumar M, Sharma J, Yuan Z. · · 2021 · cited 19× · PMID 33642391 · DOI 10.4103/1673-5374.308102