Xenazine in Late Dyskinetic Syndrome With Neuroleptics

NCT01543321 | Completed Phase 3 DMC

• 2 other identifiers: PI11-PR-KRYSTKOWIAK2011-004211-23
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 19

Brief Summary

Late dyskinetic syndrome with neuroleptics, or tardive dyskinesia, is the appearance of abnormal involuntary movements (AIM) in patients treated with antipsychotics for at least three months. This important public health issue arises for 15-20% of patients treated with neuroleptics, the most prescribed psychotropic drugs in mental disorders in France, and seriously impacts the patients' quality of life. In over 50% of cases, it is irreversible-that is to say that he will persist despite discontinuation of the offending drug. Risk factors have been described: the age and female gender are established, a higher dosage of antipsychotic, a long-term treatment, a psychiatric condition other than schizophrenia are likely risk factors, intermittent treatment, previous acute dyskinesia, neuroleptics or powerful, longer term use of corrective treatments including anticholinergics are still discussed. Apart from preventive treatment, which consists in using antipsychotics as being coerced, support is disappointing: the etiological treatment, which is to stop the offending antipsychotic, is effective only in less than 50% of cases, the syndrome is most often late irreversible. Must still have the possibility to interrupt the treatment, which is usually impossible in the risk of decompensation of the mental illness for which the neuroleptic was prescribed. Remains symptomatic treatment: functional neurosurgery is only for extreme cases, because it is not without risk, in terms of morbidity and mortality. So it's the medication that is most often offered: many drugs have been proposed, a direct result of the multiplicity of neurotransmitter systems implicated. However, in the vast majority of cases, this approach is disappointing not to say ineffective. The only exception is the tetrabenazine, marketed under the name of Xenazine®. Empirically, neurologists specializing in pathology of the movement are almost unanimous: its efficiency is very good, with good tolerance. Some preliminary studies have reinforced this impression. However, their level of evidence remains low and that is why the investigators propose to implement a prospective multicenter clinical trial, double-blind with placebo which will include two groups of 27 patients.

Conditions

Tardive Dyskinesia

Keywords

tetrabenazine; movement disorders; tardive disorders

Outcome Measures

Primary Outcomes (1)

• Changes in ESRS: Extrapyramidal Symptoms Rating Scale

  Changes in ESRS from Baseline and V6 (10 weeks after randomization) are assessed at the end of the 10 weeks of treatment.

  10 weeks after randomization

Secondary Outcomes (6)

• Changes in Sub-score ESRS-II

  At baseline (V1), V4 (7 weeks after V1), V6 (10 weeks after V1) and V7 (14 weeks after V1)

• CGI amelioration

  At baseline (V1), V4 (7 weeks after V1), V6 (10 weeks after V1) and V7 (14 weeks after V1)

• Tolerance

  within the 14 weeks of the patients' participation

• Changes in Quality of life

  At baseline (V1), V4 (7 weeks after V1), V6 (10 weeks after V1) and V7 (14 weeks after V1)

• AIMS improvement

  At baseline (V1), V4 (7 weeks after V1), V6 (10 weeks after V1) and V7 (14 weeks after V1)

Study Arms (2)

Tetrabenazine group

EXPERIMENTAL

Tetrabenazine is a drug that is administered orally. This is 25 mg tablets, divisible into 2.

Drug: Tetrabenazine

Plagebo group

PLACEBO COMPARATOR

Patients will receive a buccal tablet identical to the experimental product

Drug: Placebo

Interventions

Tetrabenazine DRUG

Treatment with tetrabenazine consists in: * 5-week titration to a maximum dose of 200 mg / day * 5 weeks at stable dose * 2 weeks in wash-out The treatment will be blinded for patients and investigators

Also known as: Xenazine (tetrabenazine)

Tetrabenazine group

Placebo DRUG

Treatment with placebo consists in: * 5-week titration to a maximum dose of 200 mg / day * 5 weeks at stable dose * 2 weeks in wash-out The treatment will be blinded for patients and investigators

Plagebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age over 18) or adult under judicial protection (tutor or curator).
• Patient with late dyskinetic syndrome with neuroleptics yielding functional disability and/or impact in every day's life, according to the investigator, and/or the patient and/or the patient's family.
• Patient with persistent late dyskinetic syndrome, even if the neuroleptic has been stopped for more than 6 months or patient with late dyskinetic syndrome under neuroleptic treatment unchanged for at least 3 months and which would a priori not need any dose variation during the study time.
• MADRS \< 18
• QTc \< 450 ms for men and \< 470 for women.

You may not qualify if:

• Lack of social insurance
• Neuroleptic treatment less than 3 months
• Insanity according to the DSM IV and MMS \< 24
• Predominant akathisia
• Psychiatric disease not stabilized for more than 6 months and/or which could require a neuroleptic treatment adaptation during study time.
• Pregnancy and lactating
• Women in genital activity without efficient contraception method (IUD or estrogen-progestin pill)
• Hypersensitivity to tetrabenazine
• Renal failure
• Drugs: Non-selective MAOIs, dopaminergic (or other antiparkinsonian)
• Other severe pathology
• Patient non compliant to protocol, at the investigator's appreciation
• Simultaneous participation to other clinical trial
• Congenital galactosemia, glucose malabsorption or lactase deficiency

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (19)

CHU Amiens

Amiens, Picardie, 80000, France

Location

CH Aix en Provence

Aix-en-Provence, 13100, France

Location

CHU Bordeaux

Bordeaux, 33076, France

Location

CHU Caen

Caen, 14033, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

CHRU Lille

Lille, 59037, France

Location

CHU Limoges

Limoges, 87042, France

Location

CH des Charpennes

Lyon, 69100, France

Location

AP-HM Hopital de la Timone

Marseille, 13385, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Nice

Nice, 06002, France

Location

CHRU de Nimes

Nîmes, 30900, France

Location

CHU Saint Antoine

Paris, 75012, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

CHU de Rennes

Rennes, 35033, France

Location

CHU Rouen

Rouen, 76031, France

Location

CHU Strasbourg

Strasbourg, 67091, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

Related Publications (1)

• Neurologies • Janvier 2012 • vol. 15 • numéro 144 page 35 http://association.gens.free.fr/NEUROLOGIA/Revues%20Neuro%20Articles/EXTRAPYRAMIDAL/$syndrome%20tardif%20aux%20neuroleptiques%204.pdf Le syndrome tardif aux neuroleptiques : quelle place pour la tétrabénazine ?

  RESULT

MeSH Terms

Conditions

Tardive Dyskinesia; Movement Disorders

Interventions

Tetrabenazine

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Dyskinesias; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinolizines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pierre Krystkowiak, MD-PhD

  University Hopsital of Amiens

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2012
• First Posted: March 2, 2012
• Study Start: May 14, 2012
• Primary Completion: May 18, 2017
• Study Completion: August 1, 2017
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

FR (19)