Parkinson DiseasePhase 1/2NCT03462641
Modulation of GABA-A Receptors in Parkinson Disease-Flumazenil Arm
A Phase 1/2 study testing Flumazenil in people with Parkinson Disease, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 99 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Flumazenil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2018to 4 Jun 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Functional Neuroimaging, Cognitive and Mobility Laboratory
Ann Arbor, Michigan, 48106
About this study
Official title: Modulation of GABA-A Receptors and Axial Motor Impairments in Parkinson Disease-Flumazenil Arm
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.
Read the detailed description
This biomechanistic GABA-A receptor target engagement study includes clinical and motor assessments before and at various time points up to approximately 90 minutes after the i.v. administration of 1 mg flumazenil and placebo in Parkinson disease subjects. Thirty Parkinson disease subjects with disease severity (Hoehn and Yahr) stages 2-4 will be recruited. Baseline [11C]FMZ and vesicular monoamine transporter type 2 (VMAT2) [11C]DTBZ brain PET imaging will be performed prior to drug administration to assess for GABA-A receptor availability and the integrity of nigrostriatal dopaminergic nerve terminals, respectively.
- Conditions
- Parkinson Disease
- Being tested
- Flumazenil, Placebo
- Keywords
- Gait, Balance, Flumazenil, PET Imaging, MRI, Mobility, Intravenous
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlumazenilDrug
1mg in 10cc normal saline
PlaceboDrug
10 cc normal saline
| Study group | Role | What they receive |
|---|---|---|
| Sequence A - (Flumazenil at Visit 1) | Experimental | A detailed 90 minute clinical assessment was conducted before and after treatment administration for each visit. Flumazenil 1mg in 10cc normal saline was given intravenously (iv) over 5-10 minutes on the first visit as treatment. 10 cc of normal saline placebo was given intravenously (iv) over 5-10 minutes on the second visit as treatment. Receives: Drug: Flumazenil; Drug: Placebo |
| Sequence B - (Placebo at Visit 1) | Experimental | A detailed 90 minute clinical assessment was conducted before and after treatment administration for each visit. 10 cc of normal saline placebo was given intravenously (iv) over 5-10 minutes on the first visit as treatment. Flumazenil 1mg in 10cc normal saline was given intravenously (iv) over 5-10 minutes on the second visit as treatment. Receives: Drug: Flumazenil; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postural Instability and Gait Disorder (PIGD) Score
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).
Measured: up to 3 hours (including pre and post infusion motor evaluation)
PIGD Score Change
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.
Measured: up to 3 hours (including pre and post infusion motor evaluation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2018
- Study start9 Mar 2018
- Primary completion4 Jun 2021
- Study completion4 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicolaas Bohnen, MD, PhD, University of Michigan
- Investigators
- Nicolaas I Bohnen, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03462641
- Sponsor's protocol ID
- HUM00130361
- Other IDs
- R01NS099535
- Status last verified
- Sep 2022
- First submitted
- 6 Mar 2018
- Last updated
- 27 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of GABA-A Receptors and Axial Motor Impairments in Parkinson Disease-Flumazenil Arm
- ClinicalTrials.gov ID
- NCT03462641
- Acronym / sponsor ID
- HUM00130361
- Conditions
- Parkinson Disease
- Keywords
- Gait, Balance, Flumazenil, PET Imaging, MRI, Mobility, Intravenous
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 9 Mar 2018 (actual)
- Primary completion
- 4 Jun 2021 (actual)
- Study completion
- 4 Jun 2021 (actual)
- First posted
- 12 Mar 2018 (actual)
- Results
- Posted 29 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This biomechanistic GABA-A receptor target engagement study includes clinical and motor assessments before and at various time points up to approximately 90 minutes after the i.v. administration of 1 mg flumazenil and placebo in Parkinson disease subjects. Thirty Parkinson disease subjects with disease severity (Hoehn and Yahr) stages 2-4 will be recruited. Baseline [11C]FMZ and vesicular monoamine transporter type 2 (VMAT2) [11C]DTBZ brain PET imaging will be performed prior to drug administration to assess for GABA-A receptor availability and the integrity of nigrostriatal dopaminergic nerve terminals, respectively.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A - (Flumazenil at Visit 1) | Experimental | Drug: Flumazenil, Drug: PlaceboA detailed 90 minute clinical assessment was conducted before and after treatment administration for each visit. Flumazenil 1mg in 10cc normal saline was given intravenously (iv) over 5-10 minutes on the first visit as treatment. 10 cc of normal saline placebo was given intravenously (iv) over 5-10 minutes on the second visit as treatment. |
| Sequence B - (Placebo at Visit 1) | Experimental | Drug: Flumazenil, Drug: PlaceboA detailed 90 minute clinical assessment was conducted before and after treatment administration for each visit. 10 cc of normal saline placebo was given intravenously (iv) over 5-10 minutes on the first visit as treatment. Flumazenil 1mg in 10cc normal saline was given intravenously (iv) over 5-10 minutes on the second visit as treatment. |
Who may qualify
- Ages
- 50 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Flumazenil1mg in 10cc normal saline | Drug | Sequence A - (Flumazenil at Visit 1), Sequence B - (Placebo at Visit 1) |
| Placebo10 cc normal saline | Drug | Sequence A - (Flumazenil at Visit 1), Sequence B - (Placebo at Visit 1) |
Primary outcome
Postural Instability and Gait Disorder (PIGD) Score
Time frame: 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).
PIGD Score Change
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaas I Bohnen, MD, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Flumazenil in people with Parkinson Disease, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postural Instability and Gait Disorder (PIGD) Score (time frame: up to 3 hours (including pre and post infusion motor evaluation)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.