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Tardive DyskinesiaPhase 3XeladysNCT01543321

Xenazine in Late Dyskinetic Syndrome With Neuroleptics

A Phase 3 study testing Tetrabenazine in people with Tardive Dyskinesia, run by Centre Hospitalier Universitaire, Amiens at 19 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tardive Dyskinesia
What is being tested?
Tetrabenazine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
19 sitesFrance
Study dates
14 May 2012to Aug 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

France19 sites

  • CH Aix en Provence

    Aix-en-Provence, 13100

  • CHU Amiens

    Amiens, Picardie, 80000

  • CHU Bordeaux

    Bordeaux, 33076

  • CHU Caen

    Caen, 14033

  • CHU Clermont-Ferrand

    Clermont-Ferrand, 63003

  • CHRU Lille

    Lille, 59037

  • CHU Limoges

    Limoges, 87042

  • CH des Charpennes

    Lyon, 69100

  • AP-HM Hopital de la Timone

    Marseille, 13385

  • CHU Montpellier

    Montpellier, 34295

  • CHU Nantes

    Nantes, 44093

  • CHU Nice

    Nice, 06002

  • CHRU de Nimes

    Nîmes, 30900

  • CHU Saint Antoine

    Paris, 75012

  • CHU Poitiers

    Poitiers, 86021

  • CHU de Rennes

    Rennes, 35033

  • CHU Rouen

    Rouen, 76031

  • CHU Strasbourg

    Strasbourg, 67091

  • CHU Toulouse

    Toulouse, 31059

Other trials in France

About this study

Official title: Study of Efficacy and Acceptability of Tetrabenazine in the Late Dyskinetic Syndrome With Neuroleptics: A Randomized, Parallel Group, Double-blind Placebo Controlled Multicentre Trial

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.

Read more

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.

Read the detailed description

Tetrabenazine is classified as a central monoamine depleting agent. In vitro studies have shown that it is an inhibitor of the vesicular monamine transporter 2 (VMAT2), resulting in synaptic dopamine depletion. This effect explains the reduction of hyperkinetic movement disorders.

Although tetrabenazine enjoys a reputation of very good efficacy in tardive syndromes, with good tolerance, it is still yet to empiricism because studies are few andf most importantly, of low level of evidence according the criteria of Evidence Based Medicine.

This is a randomized, multicenter, parallel group, double-blind placebo (tetrabenazine/placebo: 1/1), in two comparative conditions before and after 10 weeks of treatment with tetrabenazine (5-week titration to a maximum dose of 200 mg/day and 5 weeks at stable dose).

Study enrollment is proposed to patients fulfilling inclusion criteria.

The study should process as follows:

  1. Patients give their informed consent for participation after presentation of the study by the investigator.
  2. Visit V0: Given the patient's signed consent, global clinical examination, blood sampling, vital signs (weight, height, arterial tension, ECG are performed as well as a neurological examination (MMS). For women in childbearing potential, a urinary pregnancy test will be realized. It is noteworthy that a psychiatric consultation dating less than one month is required.
  3. Visit V1: patient is randomized in one of the two arms: tetrabenazine or placebo. Some tests are performed at baseline:
  • Neurologic: ESRS, AIMS, CGI, UPDRSIII, MMS;
  • Quality of life auto-questionnaires: SF36, Epworth; The treatment is prescribed following a titration phase during 5 weeks, a stable dose during 5 weeks, and a wash-out period during 2 weeks.
  1. At V2 (1 week after V1), V3 (3 weeks after V1) and V5 (7 weeks after V1): global clinical examination is performed and prescription observance is checked.
  2. At V4 (5 weeks after V1), V6 (10 weeks after V1) and V7 (12 weeks after V1): neurological (ESRS, AIMS, CGI, UPDRSIII, auto questionnaire SF36, Epworth, neuropsychological examination (MADRS), psychiatric examination (only at V6), vital signs and prescription observance.
Being tested
Tetrabenazine, Placebo
Keywords
tetrabenazine, movement disorders, tardive disorders
Medical subject headings
Tardive Dyskinesia, Movement Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TetrabenazineDrug

    Also called Xenazine (tetrabenazine)

    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

  • PlaceboDrug

    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

Study groups in NCT01543321
Study groupRoleWhat they receive
Tetrabenazine groupExperimentalTetrabenazine is a drug that is administered orally. This is 25 mg tablets, divisible into 2.
Receives: Drug: Tetrabenazine
Plagebo groupPlacebo comparatorPatients will receive a buccal tablet identical to the experimental product
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 10 weeks after randomization

Secondary outcomes (6)

  1. Changes in Sub-score ESRS-II

    ESRS-II is calculated as the ESRS total score minus ESRS sub-part II (worst score=0, best score=158).

    The choice of this sub-score is justified because of the possibility of improving the total ESRS can be masked by the induction of parkinsonian syndrome represented by part II of the ESRS that we chose to subtract in order to achieve the ESRS 2.

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

  2. CGI amelioration

    Clinical Global Impression is an ordinal scale in eight categories: unevaluated = 0; much worsened = 7

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

  3. Tolerance

    Tolerance includes:

    • neurological consultation
    • global clinical examination: ECG (QT), BP, pulse, orthostatic hypotension, weight

    Measured: within the 14 weeks of the patients' participation

  4. Changes in Quality of life

    Quality of life will be investigated with the SF36 questionnaire.

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

  5. AIMS improvement

    Expected reduction of dyskinesia during the study will be investigated with the Abnormal Involuntary Movement Scale (AIMS).

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

  6. Changes in intermediate ESRS and post-treatment ESRS

    Changes in ESRS are assessed between baseline and the end of the titration period (7 weeks after randomization) and after the wash-out period (14 weeks after randomization).

    Measured: 7 weeks after randomization and 14 weeks after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2012 (estimated)
  2. Study start14 May 2012
  3. Primary completion18 May 2017
  4. Study completionAug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01543321
Sponsor's protocol ID
PI11-PR-KRYSTKOWIAK
Other IDs
2011-004211-23
Acronym
Xeladys
Status last verified
Nov 2025
First submitted
22 Feb 2012
Last updated
19 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • 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 ?

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tetrabenazine in people with Tardive Dyskinesia, run by Centre Hospitalier Universitaire, Amiens at 19 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in ESRS: Extrapyramidal Symptoms Rating Scale (time frame: 10 weeks after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01543321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.

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