Pathophysiology of Tremor-modulating Mechanisms of Propranolol and Primidone in Essential Tremor

NCT04692844 | Completed

• 1 other identifier: 0120-525/2017
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Pathophysiology of tremor-modulating mechanisms of propranolol and primidone in essential tremor (ET) will be studied using accelerometry with electromyography (EMG), transcranial magnetic stimulation (TMS), and eyeblink conditioning paradigm (EBCC). TMS is a well-established experimental method for studying the effects of drugs on motor cortex excitability. EBCC is a learning paradigm that can be used for studying cerebellar dysfunction since only brainstem and cerebellar functions seem to be needed for this paradigm. The investigators will use TMS to study the mechanisms of primidone and propranolol action in ET, EBCC paradigm to evaluate cerebellar dysfunction in ET patients and to show whether cerebellar dysfunction influences the effectiveness of propranolol and primidone. The investigators will clinically assess patients using The Essential Tremor Rating Assessment Scale (TETRAS) and the Scale for the Assessment and Rating of Ataxia (SARA) scales. Patients with ET will be studied prior to treatment with propranolol or primidone and re-tested 3-6 months after treatment initiation. On each visit, the investigators will clinically assess the patients and perform accelerometry, TMS measurements, and the eyeblink classical conditioning (EBCC) paradigm. The investigators hypothesize that in ET patients, baseline electrophysiological parameters will differ between responders and non-responders to propranolol and primidone and that propranolol and primidone will cause a different pattern of change in electrophysiological parameters among responders. It is hypothesized that cerebellar dysfunction will negatively correlate with patients' response to treatment.

Conditions

Essential Tremor

Keywords

Essential tremor; Primidone; Propranolol

Outcome Measures

Primary Outcomes (2)

• Electrophysiological correlations of clinical effect

  Comparison of TMS and clinical measures before and after treatment, comparison of cerebellar dysfunction with response to treatment

  3-6 months

• Effect of cerebellar function assessed by eye blink classical conditioning on drug effectiveness

  Comparison of cerebellar function of responders and non-responders

  3-6 months

Study Arms (2)

Patients with essential tremor treated with Propranolol

Patients will be recruited from the outpatient clinic for extrapyramidal disorders. Only patients with the diagnosis of ET made according to the newest consensus statement on the classification of tremors and only patients who will receive Propranolol in the course of routine medical practice, will be included.

Drug: Propranolol

Patients with essential tremor treated with Primidone

Patients will be recruited from the outpatient clinic for extrapyramidal disorders. Only patients with the diagnosis of ET made according to the newest consensus statement on the classification of tremors and only patients who will receive Primidone in the course of routine medical practice, will be included.

Drug: Primidone

Interventions

Propranolol DRUG

Patients will receive Propranolol in the course of their routine treatment. Results will be used to explore biological phenomena or disease processes.

Patients with essential tremor treated with Propranolol

Primidone DRUG

Patients will receive Primidone in the course of their routine treatment. Results will be used to explore biological phenomena or disease processes.

Patients with essential tremor treated with Primidone

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the outpatient clinic for extrapyramidal disorders.

You may qualify if:

• diagnosis of essential tremor made according to the newest consensus statement on the classification of tremors
• patients initiated on propranolol or primidone

You may not qualify if:

• a history of seizures
• a history of mental illness,
• having a cardiac pacemaker
• having metal material in the head (except dental material in the mouth)
• having a medication pump
• pregnancy

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

Departmet of Neurology, University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (15)

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MeSH Terms

Conditions

Essential Tremor

Interventions

Propranolol; Primidone

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Phenobarbital; Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Maja Kojović, PhD, MD

  maja.kojovic@kclj.si

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: doc. dr. Maja Kojović, dr. med.

Study Record Dates

• First Submitted: December 29, 2020
• First Posted: January 5, 2021
• Study Start: August 28, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 13, 2023

Record last verified: 2023-04

Locations

SL (1)