Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor

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

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

Study Overview

• Status: Withdrawn
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: placebo; Drug: pramipexole

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Baranya Megye
    • Pécs, Baranya Megye, Hungary, H-7623
      • Department of Neurology, University of Pécs
  • Somogy Megye
    • Kaposvár, Somogy Megye, Hungary, H-7400
      • Kaposi Mór County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pecs
• Investigators: Principal Investigator: Norbert Kovacs, MD, PhD, Associate Professor

Publications and helpful links

General Publications

• Kovács N, Pál E, Késmárky I, Komoly S, Nagy F, Herceg M. Pramipexole for treating essential tremor. Eur J Neurol 2011;18(Suppl 2):482.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: essential tremor; cross-over; pramipexole
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: AOK_KA_2011_pramipexole; 34039/KA-OTKA/11-10 (Other Identifier: University of Pécs, Faculty of Medicine)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No