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Modulation of GABA-A Receptors in Parkinson Disease-Clarithromycin Arm (GABA-A)

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ClinicalTrials.gov Identifier: NCT03440112
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : July 4, 2019
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Nicolaas Bohnen, MD, PhD, University of Michigan

Tracking Information
First Submitted Date  ICMJE January 26, 2018
First Posted Date  ICMJE February 20, 2018
Last Update Posted Date July 4, 2019
Actual Study Start Date  ICMJE January 29, 2018
Estimated Primary Completion Date November 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2018)
Change in [11-Carbon]-flumazenil ([11C]FMZ) PET Binding [ Time Frame: 7-9 days ]
We will use brain PET imaging to assess quantitative changes in GABA-A receptors before and after the administration of clarithromycin in Parkinson disease subjects
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03440112 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2018)
Change in quantitative biomechanics [ Time Frame: 7-9 days ]
We will use the PIGD-UPDRS motor scale to assess axial motor functions before and after 7 days of clarithromycin and correlate this with the [11C]FMZ PET binding study.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Modulation of GABA-A Receptors in Parkinson Disease-Clarithromycin Arm
Official Title  ICMJE Modulation of GABA-A Receptors and Axial Motor Impairments in Parkinson
Brief Summary The arm of this study evaluates possible GABA-A receptor target engagement effects of the FDA-approved medication, clarithromycin, in the setting of Parkinson's disease. Two-thirds of the subjects will receive clarithromycin for 7-9 days, and 1/3 will receive a placebo. [11C]Flumazenil GABA-A receptor PET imaging will be used to assess target engagement effects.
Detailed Description This study focuses on neurochemical changes in the brain that occur in Parkinson's disease. In particular we will be looking a neurotransmitter called GABA. In some Parkinson's disease patients we see too much GABA activity in the brain. There is emerging in vitro and in vivo evidence that clarithromycin, an FDA-approved and orally available macrolide antibiotic, can act as a negative allosteric modulator of brain GABA-A receptors. This target engagement study examines the target engagement effect of GABA-A receptor modulation by clarithromycin. [11C]-flumazenil Positron Emission Tomography (PET) imaging results will be used to assess for possible GABA-A receptor target engagement effects of clarithromycin.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Participant, Investigator
Primary Purpose: Other
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: Clarithromycin
    Clarithromycin (generic) capsule 250mg each
    Other Name: Biaxin
  • Drug: Placebo
    Lactose in a gel capsule
Study Arms  ICMJE
  • Active Comparator: Clarithromycin
    Clarithromycin 250mg (1 capsule) will be taken orally twice a day for 3 days and if tolerated will be increased to 500mg (2 capsules) orally twice a day for 4-6 days.
    Intervention: Drug: Clarithromycin
  • Placebo Comparator: Placebo
    Placebo will be taken exactly as the clarithromycin arm: 1 capsule orally twice a day for 3 days and if tolerated will be increased to 2 capsules orally twice a day for 4-6 days.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2021
Estimated Primary Completion Date November 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, GABAB-ergic medications (baclofen, tizanidine), neuroleptic, anticholinergic (trihexphenidyl, 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.

Exclusion criteria specific for clarithromycin arm of the study

  1. Allergy or hypersensitivity to clarithromycin, other macrolide antibiotics, or similar medicines such as azithromycin, erythromycin or telithromycin.
  2. History of significant atrial or ventricular arrhythmias.
  3. Significant liver or kidney disease.
  4. Corrected QT interval (QTc) prolongation.
  5. Subjects taking digoxin, colchicine, pimozide, cisapride, quetiapine, astemizole, terfenadine, ergotamine, or dihydroergotamine.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christine Minderovic, BS 734-998-8400 cmindero@umich.edu
Contact: Catherine Dowling, MD 734-998-8400 cdowling@med.umich.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03440112
Other Study ID Numbers  ICMJE HUM00360361-A
R01NS099535 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nicolaas Bohnen, MD, PhD, University of Michigan
Study Sponsor  ICMJE Nicolaas Bohnen, MD, PhD
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Nicolaas I Bohnen, MD, PhD University of Michigan
PRS Account University of Michigan
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP