Neuroleptic-induced Tardive DyskinesiaNCT00310661
Sarizotan in the Treatment of Neuroleptic-induced Tardive Dyskinesia
A study testing Sarizotan in people with Neuroleptic-induced Tardive Dyskinesia, run by Centre for Addiction and Mental Health at 2 sites in 2 countries.
Trial summary
TD is a troublesome and potentially irreversible side effect associated with the use of neuroleptics. While the newer neuroleptics are improved in this regard, they all still carry the risk of TD. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Neuroleptic-induced Tardive Dyskinesia
- What is being tested?
- Sarizotan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2004to Mar 2008
- Phase
- Interventional
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient meets the Schooler and Kane Diagnostic Criteria (25) for Tardive Dyskinesia as established by history and physical examination.
- a score of 3 or above for item 8 of the AIMS scale (Severity of Abnormal Movements) at baseline.
- For female patients: either the patient is surgically sterile, has been post-menopausal for at least 12 months, or she is using a reliable method of contraception (single-barrier methods alone will not be considered sufficiently reliable) and provides a negative pregnancy test at the screening visit.
- on a stable dose of his/her current antipsychotic (either typical or atypical) and movement disorder medication (e.g. anticholinergics) for at least one month before randomisation. For depot antipsychotics, this period will be at least one dosing interval.
- The patient gives full written informed consent for participation in the study.
- The patient has a level of understanding of English or Tamil sufficient to communicate effectively with the investigator and study staff, and to be able to complete the computerised neurocognitive test battery where necessary
Who cannot join
- Exclusion criteria listed in the Research Criteria for Tardive Dyskinesia as defined in DSM-IV (symptoms not due to another neurological or general medical condition such as Huntington's disease, Sydenham's chorea, spontaneous dyskinesia, hyperthyroidism, Wilson's disease, ill-fitting dentures, exposure to other medications causing acute reversible dyskinesia such as L?dopa or bromocriptine).
- Evidence of pre-existing tic disorders, neuroleptic-induced acute dystonia or neuroleptic-induced acute akathisia
- Risk of suicide (in the opinion of the investigator).
- Any of the following non-permitted concomitant medication: Metoclopramide in the 4 weeks before screening, Buspirone in the 4 weeks before screening, Azole antifungals (particularly ketoconazole), Etomidate, HIV proteinase inhibitors (e.g. indinavir, ritonavir), any tricyclic antidepressant in the 4 weeks before screening (SSRI antidepressants if at a stable dosage are permitted), Fludrocortisone, Intermittent therapy with oral corticoids, continuous therapy with <7.5mg/day (oral) prednisolone or an equivalent dose of a different corticoid (patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent may participate but should not undergo an ACTH challenge test).
- Treatment with electroconvulsive therapy within six months before the first study visit.
- Known history of drug dependence (except nicotine and caffeine) or alcohol dependence within the six months before the study (three months for known drug abuse).
Show all 14Show fewer
- Evidence of any clinically significant endocrine, cardiac, renal, neurological, cerebrovascular, metabolic, gastrointestinal, immunological, allergic or respiratory disease. Patients who are not euthyroid.
- asthma or known hypersensitivity to antipsychotic drugs or ACTH
- Pregnancy or lactation.
- Any abnormal laboratory test result(s) of potential clinical significance at screening, including: Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) greater than 3 ´ upper limit of normal (ULN), Creatinine >2 ´ ULN, total bilirubin >2 ´ ULN
- Participation in another clinical study within the 30 days before the first visit of the present study.
- Plasma cortisol concentration below 18 µg/dL 60 minutes after stimulation with 250 µg ACTH1-24 (for procedure see Section 7.9). (NOTE: This exclusion criterion is waived, and the test should not be carried out, for patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent.
- Lack of legal capacity, or limited legal capacity.)
- Known previous diagnosis of learning disability.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Dual-centre, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Determine the Effects of Various Adjunctive Doses of Sarizotan in the Treatment of Patients With Neuroleptic-induced Tardive Dyskinesia
TD is a troublesome and potentially irreversible side effect associated with the use of neuroleptics. While the newer neuroleptics are improved in this regard, they all still carry the risk of TD.
The present study proposes that sarizotan is a potential agent for treating neuroleptic-induced TD based on preliminary data indicating efficacy in the management of dyskinesias associated with Parkinson's disease. Its efficacy is further substantiated by pre-clinical data obtained from the vacuous chewing movement (VCM) model in rats, a model we employ ourselves in investigating the relationship between D2 occupancy and TD. The present study also examines the effects of sarizotan on cognitive function, given the association between TD and cognitive deficits.
Read the detailed description
The primary objective of the study is to assess the safety and the anti-dyskinetic properties of sarizotan at various dosages for neuroleptic-induced TD.
The secondary objective of the study is to assess the effects of sarizotan on cognitive function in patients with neuroleptic-induced TD.
The diagnosis of neuroleptic-induced TD will be confirmed by history and physical examination. Patients will be evaluated at baseline, 2, 4, 8, and 12 weeks. Safety will be assessed by vital signs, ECG, routine blood tests, the ACTH stimulation test, and the clinician's and patient's global impression of tolerability.
Procedures:
For efficacy, the primary outcome variable will be changes in the Abnormal Involuntary Movement Scale (AIMS), and a baseline score of >3 ('moderate') will be required for item 8 (Severity of Abnormal Movements). Quantitative evaluation of movements will be carried out in two ways. The first involves a series of instrumental and clinical measures that were developed as a battery for the assessment of antipsychotic-induced parkinsonism and TD. The second means of quantifying the movements involves the use of video recording, with independent evaluation by several raters (Appendix I). Such approaches have gained popularity in the quantification of movement disorders as a means of improving reliability.
Secondary measures will include the positive and negative syndrome scale (PANSS) and other movement disorder scales (Simpson-Angus Rating Scales) for acute extrapyramidal symptoms (EPS), and the Barnes Akathisia Rating Scale (BARS). Global impressions of efficacy and tolerability by the clinician (CGI) and by the patients (PGI) will be recorded at all study visits after the commencement of treatment. To assess potential cognitive changes that may occur in conjunction with TD changes, a battery of neuropsychological tests will be carried out at baseline and endpoint (see Appendix II). To assess the relationship with primary negative symptoms such as the deficit syndrome, the total and sub-scales of the Positive and Negative Syndrome Scale will be evaluated.
- Conditions
- Neuroleptic-induced Tardive Dyskinesia
- Being tested
- Sarizotan, Placebo
- Keywords
- sarizotan, neuroleptic-induced tardive dyskinesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SarizotanDrug
Also called Sarizotan HCI
The dose of sariztan HCI for each patient in the drug arm will be given 2mg b.i.d. orally during the first 4 weeks of treatment. If efficacy is inadequate and there are no safety concerns, the option to raise the dose to 5mg b.i.d is given. After 8 weeks of treatment, the option to raise the dose to 7mg bid is given. Dose may remain the same or may be decreased again to the previous dose.
PlaceboOther
Also called Sugar Pill
Placebo for each patient randomized to the placebo arm will be given placebo (oral, twice daily) in a pill form for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo hard gelatin capsules matching the investigational medication Receives: Other: Placebo |
| Sarizotan HCI | Experimental | Sarizotan HCI is administered at various doses ranging from 2-7mg. Receives: Drug: Sarizotan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of change in the Abnormal Involuntary Movement Scale
Measured: 12 weeks
Secondary outcomes (3)
Change in PANSS
Measured: 12 weeks
Change in Simpson-Angus Rating Scales for acute EPS
Measured: 12 weeks
Change in Barnes Akathisia Rating Scale
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2006 (estimated)
- Study startDec 2004
- Primary completionSep 2006
- Study completionMar 2008
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroleptic-induced Tardive DyskinesiaStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Principal investigator, Gary Remington, Centre for Addiction and Mental Health
- Investigators
- Gary Remington, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00310661
- Sponsor's protocol ID
- 005/2004
- Status last verified
- Jul 2015
- First submitted
- 3 Apr 2006
- Last updated
- 23 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kleven MS, Barret-Grevoz C, Bruins Slot L, Newman-Tancredi A. Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology. 2005 Aug;49(2):135-43. doi: 10.1016/j.neuropharm.2005.02.005. Epub 2005 Apr 1.
PubMed 15996562
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dual-centre, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Determine the Effects of Various Adjunctive Doses of Sarizotan in the Treatment of Patients With Neuroleptic-induced Tardive Dyskinesia
- ClinicalTrials.gov ID
- NCT00310661
- Acronym / sponsor ID
- 005/2004
- Conditions
- Neuroleptic-induced Tardive Dyskinesia
- Keywords
- sarizotan, neuroleptic-induced tardive dyskinesia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Dec 2004
- Primary completion
- Sep 2006 (actual)
- Study completion
- Mar 2008
- First posted
- 4 Apr 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TD is a troublesome and potentially irreversible side effect associated with the use of neuroleptics. While the newer neuroleptics are improved in this regard, they all still carry the risk of TD.
The present study proposes that sarizotan is a potential agent for treating neuroleptic-induced TD based on preliminary data indicating efficacy in the management of dyskinesias associated with Parkinson's disease. Its efficacy is further substantiated by pre-clinical data obtained from the vacuous chewing movement (VCM) model in rats, a model we employ ourselves in investigating the relationship between D2 occupancy and TD. The present study also examines the effects of sarizotan on cognitive function, given the association between TD and cognitive deficits.
Detailed description
The primary objective of the study is to assess the safety and the anti-dyskinetic properties of sarizotan at various dosages for neuroleptic-induced TD.
The secondary objective of the study is to assess the effects of sarizotan on cognitive function in patients with neuroleptic-induced TD.
The diagnosis of neuroleptic-induced TD will be confirmed by history and physical examination. Patients will be evaluated at baseline, 2, 4, 8, and 12 weeks. Safety will be assessed by vital signs, ECG, routine blood tests, the ACTH stimulation test, and the clinician's and patient's global impression of tolerability.
Procedures:
For efficacy, the primary outcome variable will be changes in the Abnormal Involuntary Movement Scale (AIMS), and a baseline score of >3 ('moderate') will be required for item 8 (Severity of Abnormal Movements). Quantitative evaluation of movements will be carried out in two ways. The first involves a series of instrumental and clinical measures that were developed as a battery for the assessment of antipsychotic-induced parkinsonism and TD. The second means of quantifying the movements involves the use of video recording, with independent evaluation by several raters (Appendix I). Such approaches have gained popularity in the quantification of movement disorders as a means of improving reliability.
Secondary measures will include the positive and negative syndrome scale (PANSS) and other movement disorder scales (Simpson-Angus Rating Scales) for acute extrapyramidal symptoms (EPS), and the Barnes Akathisia Rating Scale (BARS). Global impressions of efficacy and tolerability by the clinician (CGI) and by the patients (PGI) will be recorded at all study visits after the commencement of treatment. To assess potential cognitive changes that may occur in conjunction with TD changes, a battery of neuropsychological tests will be carried out at baseline and endpoint (see Appendix II). To assess the relationship with primary negative symptoms such as the deficit syndrome, the total and sub-scales of the Positive and Negative Syndrome Scale will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo hard gelatin capsules matching the investigational medication |
| Sarizotan HCI | Experimental | Drug: SarizotanSarizotan HCI is administered at various doses ranging from 2-7mg. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The patient meets the Schooler and Kane Diagnostic Criteria (25) for Tardive Dyskinesia as established by history and physical examination.
- a score of 3 or above for item 8 of the AIMS scale (Severity of Abnormal Movements) at baseline.
- For female patients: either the patient is surgically sterile, has been post-menopausal for at least 12 months, or she is using a reliable method of contraception (single-barrier methods alone will not be considered sufficiently reliable) and provides a negative pregnancy test at the screening visit.
- on a stable dose of his/her current antipsychotic (either typical or atypical) and movement disorder medication (e.g. anticholinergics) for at least one month before randomisation. For depot antipsychotics, this period will be at least one dosing interval.
- The patient gives full written informed consent for participation in the study.
Key exclusion criteria (14 listed)
- Exclusion criteria listed in the Research Criteria for Tardive Dyskinesia as defined in DSM-IV (symptoms not due to another neurological or general medical condition such as Huntington's disease, Sydenham's chorea, spontaneous dyskinesia, hyperthyroidism, Wilson's disease, ill-fitting dentures, exposure to other medications causing acute reversible dyskinesia such as L?dopa or bromocriptine).
- Evidence of pre-existing tic disorders, neuroleptic-induced acute dystonia or neuroleptic-induced acute akathisia
- Risk of suicide (in the opinion of the investigator).
- Any of the following non-permitted concomitant medication: Metoclopramide in the 4 weeks before screening, Buspirone in the 4 weeks before screening, Azole antifungals (particularly ketoconazole), Etomidate, HIV proteinase inhibitors (e.g. indinavir, ritonavir), any tricyclic antidepressant in the 4 weeks before screening (SSRI antidepressants if at a stable dosage are permitted), Fludrocortisone, Intermittent therapy with oral corticoids, continuous therapy with <7.5mg/day (oral) prednisolone or an equivalent dose of a different corticoid (patients on continuous long-term therapy with a dose of >7.5mg prednisolone or equivalent may participate but should not undergo an ACTH challenge test).
- Treatment with electroconvulsive therapy within six months before the first study visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SarizotanAlso: Sarizotan HCIThe dose of sariztan HCI for each patient in the drug arm will be given 2mg b.i.d. orally during the first 4 weeks of treatment. If efficacy is inadequate and there are no safety concerns, the option to raise the dose to 5mg b.i.d is given. After 8 weeks of treatment, the option to raise the dose to 7mg bid is given. Dose may remain the same or may be decreased again to the previous dose. | Drug | Sarizotan HCI |
| PlaceboAlso: Sugar PillPlacebo for each patient randomized to the placebo arm will be given placebo (oral, twice daily) in a pill form for 12 weeks | Other | Placebo |
Primary outcome
Degree of change in the Abnormal Involuntary Movement Scale
Time frame: 12 weeks
3 secondary outcomes
Change in PANSS
Time frame: 12 weeks
Change in Simpson-Angus Rating Scales for acute EPS
Time frame: 12 weeks
Change in Barnes Akathisia Rating Scale
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: Funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2015.
- Background: PubMed 15996562Kleven MS, Barret-Grevoz C, Bruins Slot L, Newman-Tancredi A. Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology. 2005 Aug;49(2):135-43. doi: 10.1016/j.neuropharm.2005.02.005. Epub 2005 Apr 1.
- CAMH web siteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Remington, MD principal investigator
Centre for Addiction and Mental Health
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sarizotan in people with Neuroleptic-induced Tardive Dyskinesia, run by Centre for Addiction and Mental Health at 2 sites in 2 countries.
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 6 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: stopped early, as of the sponsor's last update on 23 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, India. 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.
Are results available for this study?
The study was stopped early (reason given: Funding). Results are not available in the source record.
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?
Degree of change in the Abnormal Involuntary Movement Scale (time frame: 12 weeks). 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 NCT00310661, 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 23 Jul 2015.