Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor

Study Overview
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Brief Summary
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Aim of the study is to perform a double-blind, crossover, placebo-controlled multicenter study evaluating the efficacy of pramipexole on essential tremor.

Detailed Description
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Essential tremor is one of the most common movement disorders with the prevalence of 3-5% among the elderly population. Although its main clinical feature is the bilateral, predominantly postural-kinetic tremor, newer studies suggest that ET is a spectrum of clinical features with both motor and nonmotor elements not homogeneously distributed. Despite its high occurrence, the pharmacological treatment of ET is limited. Although the mainline drugs, propranolol and primidone, can provide good clinical benefit in a portion of cases, >50% of the patients stop the medication due to inefficacy or side-effects. Hypotension, dizziness, bradycardia, cognitive impairment, fatigue and erectile dysfunction are the most common side-effects contributing to medication discontinuation. In an open-label pilot study, the investigators previously demonstrated that 2.1 mg/day pramipexole extended-release improved both the severity of tremor (by 52%) and health-related quality of life. The present study aims to confirm this hypothesis in a double-blind, crossover, placebo-controlled multicenter study.

Official Title
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Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor: a Double-blind, Cross-over, Placebo-controlled Multicenter Study

Conditions
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Essential Tremor

Intervention / Treatment
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* Drug: pramipexole
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ET has to be unambiguous based on the clinical diagnostic criteria. Tremor has to be severe enough to produce disability. Patients must sign a written informed consent according with the approval of the Regional Ethical Board of University of Pécs Exclusion Criteria: Exclusion criteria are established in accordance to the guidelines of Elble et al3. Presence of any medical conditions capable of producing tremor (e.g. hyperthyroidism, drug withdrawal, neuropathy, etc.). Except for cogwheel phenomenon, the presence of any abnormal neurological signs (e.g. dystonia, myoclonus, ataxia, parkinsonism, cerebellar or pyramidal signs, etc.) Atypical tremor appearance for ET (e.g. isolated vocal-cord tremor, orthostatic tremor, task-specific tremor, etc.) Presence or suspicion of psychogenic tremor Usage of medication capable of producing tremor (e.g. sympathomimetics, valproate, etc.) Concomitant administration of any drugs potentially capable of improving ET (e.g. antiepileptics, beta-receptor blockers). Previous neurosurgical treatment (e.g. deep brain stimulation or thalamotomy). Presence of serious concomitant disorders capable of interfering with the study (e.g. heart failure, tumorous disorders, etc.) Presence of any contraindication for pramipexole treatment (e.g. impulsive control disorder, known hypersensitivity to any components of the tablets, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Process 1<br>10 weeks of pramipexole treatment 2 weeks wash-out period (cross-over) 10 weeks placebo treatment | Drug: pramipexole<br>* pramipexole extended release, 2.1 mg pramipexole base (3.0mg pramipexole salt) once daily<br>* Other names: Mirapexin retard;Drug: placebo<br>* placebo<br>|
| Placebo Comparator: Process 2<br>10 weeks of placebo treatment 2 weeks wash-out period (cross-over) 10 weeks pramipexole treatment | Drug: pramipexole<br>* pramipexole extended release, 2.1 mg pramipexole base (3.0mg pramipexole salt) once daily<br>* Other names: Mirapexin retard;Drug: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in tremor severity | Improvement in tremor severity measured by Fahn-Tolosa-Marin Tremor Rating Scale | 10 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in quality of life | Improvement in quality of life assessed by EQ-5D score | 10 weeks of treatment | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 10 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pramipexole, essential tremor, cross-over