Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01MH067806 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will assess the effectiveness of pimozide in enhancing the effects of clozapine in the treatment of schizophrenia.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| placebo | Placebo Comparator | Participants will receive encapsulated placebo made to match active drug |
|
| pimozide | Experimental | Participants will receive pimozide flexible dosing |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pimozide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Variable change from baseline to week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Joseph I. Friedman, MD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States | ||
| Manhattan Psychiatric Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9285089 | Background | 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. | |
| 21346734 | Result | Friedman 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. |
Not provided
Not provided
16 subjects were excluded during the 4-week symptom stability-screening period before randomization because of withdrawal of consent or a failure to meet inclusion and exclusion criteria. Seven additional subjects were randomized to a haloperidol adjunctive pilot study.
Subjects recruited from inpatient and outpatient treatment settings at Mount Sinai Hospital, Pilgrim Psychiatric Center and Manhattan Psychiatric Center in New York.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received encapsulated placebo made to match active drug |
| FG001 | Pimozide | Participants received pimozide flexible dosing |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received encapsulated placebo made to match active drug |
| BG001 | Pimozide | Participants received pimozide flexible dosing |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | Variable change from baseline to week 12 |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received encapsulated placebo made to match active drug |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe EPS | Nervous system disorders | Systematic Assessment |
Neither baseline nor follow-up clozapine plasma concentrations were reported. Possible that one or both groups did not have therapeutic baseline clozapine levels and/or had pharmacokinetic interactions with the study drug changing concentrations.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joseph I. Friedman | Icahn School of Medicine at Mount Sinai | 631-761-3607 | joseph.friedman@mssm.edu |
Not provided
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D010868 | Pimozide |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Placebo | Drug | 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. |
|
|
| variable change from baseline to week 12 |
| New York |
| New York |
| 10035 |
| United States |
| Pilgrim Psychiatric Center | W. Brentwood | New York | 11717 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Treatment Setting | Number | participants |
|
| Pimozide |
Participants received pimozide flexible dosing |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | variable change from baseline to week 12 |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | Variable change from baseline to week 12 |
|
|
|
| 0 |
| 28 |
| 5 |
| 28 |
| EG001 | Pimozide | Participants received pimozide flexible dosing | 0 | 25 | 3 | 25 |
| delirium | Renal and urinary disorders | Systematic Assessment |
|
| bleeding | Gastrointestinal disorders | Systematic Assessment | exacerbation of hemorrhoidal bleeding |
|
| psychotic symptoms | Psychiatric disorders | Systematic Assessment |
|
| bigeminy | Cardiac disorders | Systematic Assessment |
|
| hypotension | Cardiac disorders | Systematic Assessment |
|
| withdrew consent | Social circumstances | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D002241 | Carbohydrates |