Electrophysiological and Neuroimaging Correlates of the Effect of Zolpidem in Patients With Focal Dystonia

NCT04692285 | Completed Phase 1

• 1 other identifier: 0120-232/2016
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

Brief Summary

To study electrophysiological and imaging correlations of the clinical effectiveness of zolpidem in task-specific dystonia and to elucidate mechanisms underlying its therapeutic effects, patients with focal dystonia will be clinically evaluated and will undergo transcranial magnetic stimulation and FDG-PET CT brain imaging after a single 5 mg dose of zolpidem and placebo, in two separate sessions. Resting motor threshold (RMT), active motor threshold (AMT), resting and active input/output (IO) curve, short-interval intracortical inhibition (SICI) curve, long interval intracortical inhibition (LICI), intracortical facilitation (ICF), and cortical silent period (CSP) will be measured. Objective clinical improvement will be rated using Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) and writer's cramp rating scale (WCRS). Subjective improvement will be measured using the visual analog scale (VAS). Only a subset of patients (10 patients) will undergo positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG PET) brain imaging after a single 5 mg dose of zolpidem and placebo.

Conditions

Focal Dystonia

Keywords

writer's cram; musician dystonia; TMS; zolpidem

Outcome Measures

Primary Outcomes (2)

• Change in the transcranial magnetic stimulation measures between zolpidem 5 mg and placebo

  Transcranial magnetic stimulation measures (resting and active cortical motor threshold, resting and active input-output curve, short intracortical inhibition, long intracortical inhibition, intracortical facilitation) after zolpidem 5 mg and placebo will be compared.

  30 minutes after the intervention

• Change in brain metabolism detected on FDG-PET CT brain imaging between zolpidem 5 mg and placebo

  FDG-PET CT brain imaging

  30 minutes after the intervention

Secondary Outcomes (1)

• Change in The Burke-Fahn-Marsden Dystonia Rating Scale (BFMS) between zolpidem 5 mg and placebo

  30 minutes after the intervention

Other Outcomes (2)

• Change in The Writer's Cramp Rating Scale (WCRS) between zolpidem 5 mg and placebo

  30 minutes after the intervention

• Change in the Visual Analog Score between zolpidem 5 mg and placebo

  30 minutes after the intervention

Study Arms (2)

Patients with focal dystonia treatment first placebo second

ACTIVE COMPARATOR

Zolpidem 5 mg single dose

Drug: Zolpidem

Patients with focal dystonia placebo first treatment second

PLACEBO COMPARATOR

Placebo 5 mg single dose

Drug: Placebo

Interventions

Zolpidem DRUG

Patients will undergo transcranial magnetic stimulation, 18F-FDG-PET brain imaging, and clinical testing after a single 5 mg dose of Zolpidem.

Patients with focal dystonia treatment first placebo second

Placebo DRUG

Patients will undergo transcranial magnetic stimulation, 18F-FDG-PET brain imaging, and clinical testing after a single dose of placebo.

Patients with focal dystonia placebo first treatment second

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of writer's cramp or musician dystonia

You may not qualify if:

• Patients treated with botulinum toxin within the last 3 months
• Patients with contraindications for TMS
• Patients taking benzodiazepines, zolpidem or other sedative drugs 48 hours prior to the experiment

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• Slovenian Research Agency: collaborator
• Clinical Centre of Serbia: collaborator

Study Sites (2)

University Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Departmet of Neurology, University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (4)

• Lehericy S, Tijssen MA, Vidailhet M, Kaji R, Meunier S. The anatomical basis of dystonia: current view using neuroimaging. Mov Disord. 2013 Jun 15;28(7):944-57. doi: 10.1002/mds.25527.

  PMID: 23893451 BACKGROUND

• Kapogiannis D, Wassermann EM. Transcranial magnetic stimulation in Clinical Pharmacology. Cent Nerv Syst Agents Med Chem. 2008 Dec;8(4):234-240. doi: 10.2174/187152408786848076.

  PMID: 19122782 BACKGROUND

• Quartarone A, Hallett M. Emerging concepts in the physiological basis of dystonia. Mov Disord. 2013 Jun 15;28(7):958-67. doi: 10.1002/mds.25532.

  PMID: 23893452 BACKGROUND

• Thenganatt MA, Jankovic J. Treatment of dystonia. Neurotherapeutics. 2014 Jan;11(1):139-52. doi: 10.1007/s13311-013-0231-4.

  PMID: 24142590 BACKGROUND

MeSH Terms

Conditions

Dystonic Disorders

Interventions

Zolpidem

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Maja Kojović, PhD, MD

  University Medical Centre Ljubljana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: doc. dr. Maja Kojović, dr. med.

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: December 31, 2020
• Study Start: September 30, 2017
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1); SE (1)