Efficacy Trial of Zonisamide for Myoclonus Dystonia (EpsilonZêta)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01806805
First received: March 6, 2013
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

Myoclonus Dystonia is a disease in which myoclonus distort the precision of movements and so cause a handicap in the movements of the everyday life. Response to oral medications may be incomplete and surgery may cause operating risk.

Zonisamide is an antiepileptic drug which could bring a therapeutic profit in Myoclonus Dystonia on the severity of the myoclonus.


Condition Intervention Phase
Myoclonus Dystonia
Drug: zonegran
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparative Study of the Efficiency of Zonisamide in Myoclonus Dystonia: A Monocentric , Randomized in Cross Over and Double Blind Study Versus Placebo Study

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Measure of the evolution of the severity of myoclonus by a specific scale (UMRS) [ Time Frame: from day 0 to week 23 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure of the evolution of the severity of dystonia by a specific scale (BFM) [ Time Frame: from day 0 to week 23 ] [ Designated as safety issue: No ]
  • measure of the evolution of the severity of myoclonus by electromyographic recording [ Time Frame: from day 0 to week 23 ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: February 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zonegran
Zonegran / Placebo Zonisamide (Zonegran ®) and its placebo appear under the shape of virgin capsules of size 1. Each drug will be dispensed successively in a box containing blister packs of 14 capsules. For every period (A and B), box will contain 26 blister packs. A phase of progressive increase of doses by stages of 50 mg / week is planned before reaching the fixed dose of 300 in the daytime during 4 weeks. Then, a progressive diminution over two weeks is planned before the stop.
Drug: zonegran Drug: placebo
Placebo Comparator: placebo
Placebo /Experimental Zonisamide (Zonegran ®) and its placebo appear under the shape of virgin capsules of size 1. Each drug will be dispensed successively in a box containing blister packs of 14 capsules. For every period (A and B), box will contain 26 blister packs. A phase of progressive increase of doses by stages of 50 mg / week is planned before reaching the fixed dose of 300 in the daytime during 4 weeks. Then, a progressive diminution over two weeks is planned before the stop.
Drug: zonegran Drug: placebo

Detailed Description:

In "dystonia", the involuntary abnormal movements cause a driving handicap and a change of the quality of life. A particular shape of dystonia, the Myoclonus Dystonia, is characterized by the ascendancy of myoclonias (abrupt and brief movements) associated with the abnormal dystonia. Myoclonus is an additional source of handicap in the movements of the everyday life, because they distort the precision of movements. Response to oral medications may be incomplete and the tolerance poor, such that deep brain stimulation (DBS) surgery is useful for the major forms but it is also an invasive therapeutics which the operating risk is not totally estimated in the absence of controlled study. Therefore, it is necessary to investigate other pharmacological therapeutic tracks which present a good ratio profit / risk.

Zonisamide is usually used in France in the epilepsy's treatment. It showed its efficiency in the progressive myoclonus epilepsy, not only on the seizure but also on the myoclonia. Therefore, it showed its efficiency on post-anoxic and propriospinal myoclonus. So, we make the hypothesis that this medicine could bring a therapeutic profit in the Myoclonus Dystonia.

The aim of this study is to demonstrate the efficiency of the zonisamide on the severity of myoclonus (UMRS) at those patients. The others outcomes are to estimate the impact of the treatment on the myoclonus's neurophysiological characteristics, the dystonia's severity (BFM score), the quality of life (SF-36 and CGI scores), but also to investigate the tolerance of the treatment.

We conducted a randomized, placebo-controlled, double-blind, two-period cross-over design to evaluate the effect on severity of myoclonus in response to placebo or zonisamide (until 300 mg) in 32 patients.

The study includes an evaluation at the beginning and at the end of every period (4 evaluations at all). Each period includes a phase of titration (six weeks) followed by a phase of fixed dose (three weeks). Those two periods are separated by a period of wash-out (3 weeks) preceded by a phase of progressive decrease of doses (two weeks).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Age >18 and < 60
  • Diagnosis of myoclonus dystonia including the isolated myoclonus caused by epsilon-sarcoglycans mutation or deletion.
  • Myoclonus present in both hands
  • Myoclonus decrease quality of life
  • Insufficient efficiency of the benzodiazepine's tolerated maximal dose during one year
  • Agreement to use a medically acceptable method of contraception throughout the study for female of childbearing potential
  • Normal physical and neurological examination, except myoclonus dystonia
  • No hepatic disease
  • No renal disease
  • Able to comply with study visits and procedures
  • Has voluntarily signed consent form
  • Taking no medications or stable doses medication for 4 weeks prior to the Baseline visit

Exclusion criteria :

  • Patients who are not enrolled at social security
  • Individual who have MMS ≤ 24/30 or patients legally protected or inability to provide an informed consent
  • Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
  • Weight < 40 kg
  • history of serious psychiatric illness
  • history of renal stones
  • history of allergy to sulfonamides
  • taking medications : topiramate, rifampicin, ketoconazole, cimetidine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01806805

Contacts
Contact: Emmanuel Roze, MD, PhD +33(0) 1 42 16 15 48

Locations
France
Pitié salpetriere hospital Recruiting
Paris, France, 75013
Contact: Emmanuel Roze, MD, PHD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Emmanuel Roze APHP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01806805     History of Changes
Other Study ID Numbers: P091104
Study First Received: March 6, 2013
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Movement disorder
Myoclonus dystonia
DYT 11
Antiepileptic drugs
Zonisamide
Clinical Trial
Double-mind method

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Myoclonus
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Zonisamide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014