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Trial record 9 of 16 for:    parkinson NINDS | Recruiting, Not yet recruiting, Available Studies

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

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ClinicalTrials.gov Identifier: NCT03462641
Recruitment Status : Recruiting
First Posted : March 12, 2018
Last Update Posted : March 13, 2018
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Nicolaas Bohnen, MD, PhD, University of Michigan

Brief 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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Flumazenil Drug: Placebo Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: Modulation of GABA-A Receptors and Axial Motor Impairments in Parkinson Disease-Flumazenil Arm
Actual Study Start Date : March 9, 2018
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : November 15, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Flumazenil
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Flumazenil
Flumazenil 1mg in 10cc normal saline will be given intravenously (iv) over 5-10 minutes and a detailed clinical assessment will follow for the next 90 minutes.
Drug: Flumazenil
1mg in 10cc normal saline
Placebo Comparator: Placebo
10 cc of normal saline placebo will be given intravenously (iv) over 5-10 minutes and a detailed clinical assessment will follow for the next 90 minutes.
Drug: Placebo
10 cc normal saline



Primary Outcome Measures :
  1. Change in quantitative biomechanics [ Time Frame: up to 3 hours (including pre- and post-infusion motor testing) ]
    We will use the PIGD-UPDRS motor scale to assess axial motor functions before and after 1mg flumazenil iv and correlate this with the [11-Carbon]-flumazenil ([11C]FMZ) PET binding.



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Ages Eligible for Study:   50 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Parkinson's disease (PD): PD diagnosis will follow the UK Parkinson's Disease Society Brain Bank Research Center (UKPDSBRC) clinical diagnostic criteria for PD.
  2. Hoehn and Yahr stages 2-4
  3. Absence of dementia confirmed by cognitive testing.
  4. Abnormal 11C-Dihydrotetrabenazine ([11C]-DTBZ) PET study to demonstrate nigrostriatal dopaminergic denervation.

Exclusion Criteria:

  1. PD with Dementia (PDD) or dementia with Lewy bodies (DLB).
  2. 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.
  3. Subjects on benzodiazepine, GABA-ergic medications (baclofen, tizanidine), neuroleptic, anticholinergic (trihexyphenidyl, benztropine), or cholinesterase inhibitor drugs.
  4. Evidence of a mass lesion on structural brain imaging (MRI).
  5. 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.
  6. Severe claustrophobia precluding MR or PET imaging.
  7. Subjects limited by participation in research procedures involving ionizing radiation.
  8. Pregnancy (urine or serum pregnancy test within 48 hours of each PET session) or breastfeeding.
  9. History of seizures
  10. Significant anxiety or history of panic disorder.
  11. History of recent suicide attempt or overdose of tricyclic antidepressants or other medications
  12. Any other medical history determined by investigators to preclude safe participation.
  13. Allergy to flumazenil
  14. Significant liver disease
  15. History of alcohol or other substance abuse within past two years.
  16. History of regular benzodiazepine use within past year

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03462641


Contacts
Contact: Christine Minderovic, BS 734-998-8400 cmindero@umich.edu
Contact: Catherine Dowling, MD 734-998-8400 cdowling@med.umich.edu

Locations
United States, Michigan
University of Michigan Functional Neuroimaging, Cognitive and Mobility Laboratory Recruiting
Ann Arbor, Michigan, United States, 48106
Contact: Martijn Muller, Ph.D.    734-998-8400    mtmuller@umich.edu   
Contact: Cyrus Sarosh, B.S.    734-998-8400    csarosh@umich.edu   
Principal Investigator: Nicolaaas Bohnen, MD PhD         
Sponsors and Collaborators
University of Michigan
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Nicolaas I Bohnen, MD, PhD University of Michigan

Responsible Party: Nicolaas Bohnen, MD, PhD, Professor of Radiology and Neurology, University of Michigan
ClinicalTrials.gov Identifier: NCT03462641     History of Changes
Other Study ID Numbers: HUM00130361
R01NS099535 ( U.S. NIH Grant/Contract )
First Posted: March 12, 2018    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nicolaas Bohnen, MD, PhD, University of Michigan:
Gait
Balance
Flumazenil
PET Imaging
MRI
Mobility
Intravenous

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Flumazenil
Antidotes
Protective Agents
Physiological Effects of Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action