SchizophreniaPhase 4NCT00158223
Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
A Phase 4 study testing Pimozide in people with Schizophrenia and Psychotic Disorders, run by Icahn School of Medicine at Mount Sinai at 3 sites in United States.
Trial summary
This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Psychotic Disorders
- What is being tested?
- Pimozide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2004to Feb 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of schizophrenia according to DSM-IV criteria
- Any schizoaffective disorder or subtype
- Score greater than 60 on the Positive and Negative Syndrome Scale (PANSS)
- Currently taking clozapine
- Score of four or higher on two or more items from the positive symptom subscale of the PANSS
- Score of 4 or greater on the Clinical Global Impression (CGI) scale
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- Clozapine plasma level greater than 378 µg/ml
- Stable dose of clozapine demonstrated to have been associated with a clozapine plasma level greater than 378 µg/ml for at least eight weeks
- Able to read at an 8th grade level or above
Who cannot join
- History of unstable coronary artery disease
- Congestive heart failure
- History of long Q-T syndrome
- History of cardiac arrhythmia
- History of cardiac conduction delay
- Baseline QT correction score greater than 0.425 seconds
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- Liver disease
- History of stroke
- History of Neuroleptic Malignant Syndrome
- Hypokalemia
- Hypocalcemia
- Current blindness, deafness, language difficulties, or any other disability which may prevent participation or cooperation in the study
- Current suicidal or homicidal thoughts
- Currently abusing psychoactive substances
- Currently receiving antidepressants, thymoleptics, L-DOPA, buspirone, or antipsychotics other than clozapine (Valproic acid and Divalproex sodium are not criteria for exclusion)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Manhattan Psychiatric Center
New York, New York, 10035
Pilgrim Psychiatric Center
W. Brentwood, New York, 11717
About this study
Official title: Pimozide Augmentation of Clozapine in Schizophrenia
This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
Read the detailed description
A significant number of schizophrenics exhibit partial or no response to typical antipsychotic medications. Clozapine has been shown to be more effective in treating schizophrenia than typical antipsychotic drugs. However, only an estimated 30% to 60% of people who are unresponsive to treatment with typical antipsychotics will respond to treatment with clozapine. Taking clozapine with pimozide, an antipsychotic drug, can increase clozapine's effects. However, sufficient research on this approach has not yet been performed. This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
Participants in this double-blind study will receive a stable dose of clozapine for eight weeks prior to enrollment. For the first 4 weeks following enrollment, baseline measurements will be taken. Once a week, participants will report to the study site, where symptom severity, cognitive ability, and functional status, including reading level, will be assessed. In addition, participants will receive a standard medical examination, which will include blood tests and an EKG. Upon completion of this initial phase, participants will be randomly assigned to one of two treatment groups: clozapine combined with pimozide; or clozapine combined with placebo. This phase will last for 12 weeks. Study visits will continue to occur weekly, and will be used to re-assess the measurements obtained during baseline. In addition, participants will have an EKG at each study visit for the first 4 weeks of treatment. All baseline measurements will be repeated in Week 12.
- Conditions
- Schizophrenia, Psychotic Disorders
- Being tested
- Pimozide, Placebo
- Keywords
- Schizophrenia, Clozapine, Treatment, Combination, Unresponsive, Schizoaffective Disorders
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimozideDrug
Also called Orap
Each capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects.
PlaceboDrug
Also called Sugar Pill
Active drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment.
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Participants will receive encapsulated placebo made to match active drug Receives: Drug: Placebo |
| pimozide | Experimental | Participants will receive pimozide flexible dosing Receives: Drug: Pimozide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive Syndrome Scale (PANSS) Total Score
Severity of positive schizophrenic symptoms The Positive Syndrome Scale of the PANSS is comprised of seven items measuring positive such symptoms such as hallucinations, delusions, grandiosity, etc. Each item is scored on a 7 point scale of that particular symptom's severity, ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The PANSS Positive Subscale seven items has a range of a summed score from 7 (absent) to 49 (extreme psychopathology). Therefore, the higher the score, the more severe the symtpoms.
Measured: Variable change from baseline to week 12
Negative Syndrome Scale (PANSS) Total Score
Severity of negative schizophrenic symptoms, The Negative Syndrome scale is compromised of seven items, each scored on severity with numeric assignments ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The items which comprise the Negative Syndrome Scale of the PANSS measure things such as emotional withdrawal, apathy, difficulty in abstract thinking, etc. The seven items which comprise the PANSS Negative Subscale has an aggregate range of 7 (absent) to 49 (extreme psychopathology), a higher score indicating more severe symptoms.
Measured: Variable change from baseline to week 12
Secondary outcomes (1)
Clinical Global Impression of Change (CGIC)
The Clinical Global Impression-improvement (CGI-improvement) scale is a research rating tool, developed for use in NIMH-sponsored clinical trials provides a brief assessment of the clinician's view of the patient's overall clinical improvement prior to and after initiating a study medication. The CGI-change is rated on a seven point scale ranging from 1= very much improved since the initiation of treatment to 7=very much worse since the initiation of treatment. Therefore, a lower score indicates more improvement in symptoms over time.
Measured: variable change from baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startOct 2004
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Joseph Friedman, Icahn School of Medicine at Mount Sinai
- Investigators
- Joseph I. Friedman, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00158223
- Sponsor's protocol ID
- GCO 02-0517
- Other IDs
- R01MH067806
- Status last verified
- Apr 2015
- First submitted
- 7 Sep 2005
- Last updated
- 9 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Friedman J, Ault K, Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry. 1997 Sep 15;42(6):522-3. doi: 10.1016/S0006-3223(97)00227-8. No abstract available.
PubMed 9285089Friedman JI, Lindenmayer JP, Alcantara F, Bowler S, Parak M, White L, Iskander A, Parrella M, Adler DN, Tsopelas ND, Tsai WY, Novakovic V, Harvey PD, Davis KL, Kaushik S. Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacology. 2011 May;36(6):1289-95. doi: 10.1038/npp.2011.14. Epub 2011 Feb 23.
PubMed 21346734
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pimozide Augmentation of Clozapine in Schizophrenia
- ClinicalTrials.gov ID
- NCT00158223
- Acronym / sponsor ID
- GCO 02-0517
- Conditions
- Schizophrenia, Psychotic Disorders
- Keywords
- Schizophrenia, Clozapine, Treatment, Combination, Unresponsive, Schizoaffective Disorders
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2004
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Posted 9 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
Detailed description
A significant number of schizophrenics exhibit partial or no response to typical antipsychotic medications. Clozapine has been shown to be more effective in treating schizophrenia than typical antipsychotic drugs. However, only an estimated 30% to 60% of people who are unresponsive to treatment with typical antipsychotics will respond to treatment with clozapine. Taking clozapine with pimozide, an antipsychotic drug, can increase clozapine's effects. However, sufficient research on this approach has not yet been performed. This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
Participants in this double-blind study will receive a stable dose of clozapine for eight weeks prior to enrollment. For the first 4 weeks following enrollment, baseline measurements will be taken. Once a week, participants will report to the study site, where symptom severity, cognitive ability, and functional status, including reading level, will be assessed. In addition, participants will receive a standard medical examination, which will include blood tests and an EKG. Upon completion of this initial phase, participants will be randomly assigned to one of two treatment groups: clozapine combined with pimozide; or clozapine combined with placebo. This phase will last for 12 weeks. Study visits will continue to occur weekly, and will be used to re-assess the measurements obtained during baseline. In addition, participants will have an EKG at each study visit for the first 4 weeks of treatment. All baseline measurements will be repeated in Week 12.
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 | Drug: PlaceboParticipants will receive encapsulated placebo made to match active drug |
| pimozide | Experimental | Drug: PimozideParticipants will receive pimozide flexible dosing |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of schizophrenia according to DSM-IV criteria
- Any schizoaffective disorder or subtype
- Score greater than 60 on the Positive and Negative Syndrome Scale (PANSS)
- Currently taking clozapine
- Score of four or higher on two or more items from the positive symptom subscale of the PANSS
Key exclusion criteria (15 listed)
- History of unstable coronary artery disease
- Congestive heart failure
- History of long Q-T syndrome
- History of cardiac arrhythmia
- History of cardiac conduction delay
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 |
|---|---|---|
| PimozideAlso: OrapEach capsule of active treatment will contain 2 mg of pimozide. Dosing will be flexible and will range from a minimum of 2 mg per day to 8 mg per day. Dosing will begin at Week 1 with 1 capsule per day. This will be slowly titrated at a rate of 1 capsule per week to a maximum of 4 capsules depending upon clinical response and side effects. | Drug | pimozide |
| PlaceboAlso: Sugar PillActive drug and placebo will be encapsulated in an identical fashion. The placebo capsule will be made to match in appearance and weight. There will be flexible dosing, allowing a minimum of 1 capsule per day to 4 capsules per day, in order to match the dosing range of the active treatment. | Drug | placebo |
Primary outcome
Positive Syndrome Scale (PANSS) Total Score
Time frame: Variable change from baseline to week 12
Severity of positive schizophrenic symptoms The Positive Syndrome Scale of the PANSS is comprised of seven items measuring positive such symptoms such as hallucinations, delusions, grandiosity, etc. Each item is scored on a 7 point scale of that particular symptom's severity, ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The PANSS Positive Subscale seven items has a range of a summed score from 7 (absent) to 49 (extreme psychopathology). Therefore, the higher the score, the more severe the symtpoms.
Negative Syndrome Scale (PANSS) Total Score
Time frame: Variable change from baseline to week 12
Severity of negative schizophrenic symptoms, The Negative Syndrome scale is compromised of seven items, each scored on severity with numeric assignments ranging from 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate severe, 6 = severe, and 7 = extreme. The items which comprise the Negative Syndrome Scale of the PANSS measure things such as emotional withdrawal, apathy, difficulty in abstract thinking, etc. The seven items which comprise the PANSS Negative Subscale has an aggregate range of 7 (absent) to 49 (extreme psychopathology), a higher score indicating more severe symptoms.
1 secondary outcome
Clinical Global Impression of Change (CGIC)
Time frame: variable change from baseline to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9285089Friedman J, Ault K, Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry. 1997 Sep 15;42(6):522-3. doi: 10.1016/S0006-3223(97)00227-8. No abstract available.
- Results publication: PubMed 21346734Friedman JI, Lindenmayer JP, Alcantara F, Bowler S, Parak M, White L, Iskander A, Parrella M, Adler DN, Tsopelas ND, Tsai WY, Novakovic V, Harvey PD, Davis KL, Kaushik S. Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacology. 2011 May;36(6):1289-95. doi: 10.1038/npp.2011.14. Epub 2011 Feb 23.
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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.
Joseph I. Friedman, MD principal investigator
Icahn School of Medicine at Mount Sinai
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pimozide in people with Schizophrenia and Psychotic Disorders, run by Icahn School of Medicine at Mount Sinai at 3 sites in United States.
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 9 inclusion and 15 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 9 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Positive Syndrome Scale (PANSS) Total Score (time frame: Variable change from baseline to week 12). The study lists 2 primary outcomes in all. 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 NCT00158223, which also lists 2 linked publications.
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 9 Apr 2015.