SchizophreniaPhase 4NCT01401491
Treatment Strategy for Refractory Schizophrenia: Drug Interaction Between Clozapine and Fluvoxamine
A Phase 4 study testing clozapine plus fluvoxamine in people with Schizophrenia, run by Taipei Medical University Hospital at 1 site in Taiwan.
Trial summary
Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- clozapine plus fluvoxamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2008to Dec 2010
- Phase
- Phase 4
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Inpatients meet the DSM-IV criteria for schizophrenia.
- Treatment refractoriness: Failed to respond to at least two typical neuroleptics at dosage equivalent to or greater than 1000 mg/day of chlorpromazine for a period of at least six weeks.
- Age 18-60 years.
- Males or females.
- Total PANSS score >60
- Good physical health determined by complete physical examination, laboratory tests, and EKG.
- Capacity and willingness to give written informed consent.
Who cannot join
- History of illicit substance abuse or dependence
- History of clozapine intolerance (such as clinically significant leukopenia or agranulocytosis).
- Patients with WBC count less than 3500/mm3 or ANC count less than 2000/mm3will not be included.
- Any depot neuroleptics within 30 days before the day of randomization.
- Epilepsy, active hepatitis, HIV positivity, or current myeloproliferative disorder. Other medical illnesses may necessitate subjects' exclusion after evaluation of individual cases by the principal investigator and other staffs. Clinical judgment will be used.
Trial locations and contacts
1 site in 1 country.
About this study
Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. There are patients who do not respond to clozapine, and the need to treat these severely ill patients frequently compels clinicians to adopt therapeutic innovations that lack a sound empirical basis. One strategy is the combination of various other somatic treatments with clozapine.
Recently, the investigators conduct a preliminary open trial to evaluate the safety and efficacy of fluvoxamine coadministration with clozapine in refractory schizophrenic patients. The combined treatment is well tolerated, and clinical improvement is observed in our patients. And the concomitant fluvoxamine could attenuate the clozapine-induced weight gain and metabolic disturbance. However, the effects of fluvoxamine on the safety and therapeutic efficacy of clozapine need to be further clarified in double-blind study.
Read the detailed description
Background Schizophrenia is one of the most severe mental illnesses. The prevalence of schizophrenia has been variously reported as ranging from 1 to 1.5 percent. More than 50% of patients can be described as having a poor outcome, with repeated hospitalizations, exacerbations of symptoms, episodes of major mood disorders, and suicide attempts. Schizophrenia is costly in medical care, treatment and rehabilitation, and reduced or lost productivity. Therefore, the development of effective treatment for schizophrenic patients is an important issue.
The classical antipsychotic drugs are the dopamine receptor antagonists, which are effective in the treatment of schizophrenia, particularly of the positive symptoms. Even with treatment of typical antipsychotics, about 50% of schizophrenic patients lead severely debilitated lives. Second, the classical antipsychotic drugs are associated with annoying and serious adverse effects. Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. There are patients who do not respond to clozapine, and the need to treat these severely ill patients frequently compels clinicians to adopt therapeutic innovations that lack a sound empirical basis. One strategy is the combination of various other somatic treatments with clozapine.
Recently, the investigators conduct a preliminary open trial to evaluate the safety and efficacy of fluvoxamine coadministration with clozapine in refractory schizophrenic patients. The mean plasma clozapine levels obtained by clozapine 100 mg/day plus fluvoxamine 50 mg/day is close to that produced by 300-mg/day clozapine monotherapy in one of our previous studies. The combined treatment is well tolerated, and clinical improvement is observed in our patients. And the concomitant fluvoxamine could attenuate the clozapine-induced weight gain and metabolic disturbance. However, the effects of fluvoxamine on the safety and therapeutic efficacy of clozapine need to be further clarified in double-blind study.
Methods This study is a three-year proposal. Sixty treatment-resistant schizophrenic inpatients will participate in this project. The subjects will be randomized to one of two parallel groups: clozapine monotherapy and clozapine plus fluvoxamine treatment. The double-blind active treatment will consist of two periods.
The measures of clinical efficacy will be the Positive And Negative Syndrome Scale, Clinical Global Impression, and Nurses'Observation Scale for Inpatient Evaluation. The measures of side effects will be the Extrapyramidal Symptom Rating Scale and the UKU Side Effect Rating Scale. Fasting serum samples are collected to determine the lipid profile (total cholesterol, triglycerides, HDL, and LDL), glucose level, and insulin level. Plasma levels of clozapine, norclozapine, and clozapine N-oxide will be determined by high performance liquid chromatography with ultraviolet detection.
The following results are expected:
- In treatment-resistant schizophrenic patients, global antipsychotic effect of clozapine plus fluvoxamine treatment is superior to clozapine monotherapy.
- Clozapine plus fluvoxamine treatment has less adverse effects than clozapine monotherapy.
- The effect of clozapine plus fluvoxamine treatment on body weight and metabolic disturbances is superior to clozapine monotherapy.
- Steady-state plasma levels of clozapine and its metabolites account for a proportion of variance of clinical effects.
- Conditions
- Schizophrenia
- Being tested
- clozapine plus fluvoxamine, clozapine plus placebo
- Keywords
- schizophrenia, clozapine, fluvoxamine, metabolic syndrome
- Medical subject headings
- Schizophrenia, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clozapine plus fluvoxamineDrug
clozapine 100 mg/day plus fluvoxamine 50 mg/day
clozapine plus placeboDrug
clozapine 300 mg/day plus placebo
| Study group | Role | What they receive |
|---|---|---|
| clozapine + fluvoxamine | Active comparator | Not described Receives: Drug: clozapine plus fluvoxamine |
| clozapine + placebo | Placebo comparator | Not described Receives: Drug: clozapine plus placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the changes in the psychopathology during the trial
The changes in the scores of psychopathology assessment (the Positive and Negative Syndrome Scale, PANSS)
Measured: every 2 weeks
the changes in the metabolic syndrome parameters during the trial
The changes in the metabolic syndrome parameters
Measured: every 2 weeks
Secondary outcomes (4)
the changes in the plasma drug levels
the plasma levels of fluvoxamine, clozapine, and its metabolites
Measured: every 2 weeks
The changes in insulin levels
The changes in insulin levels
Measured: every 2 weeks
The changes in the depression severity
The changes in the scores of the Hamilton Rating Scale for Depression
Measured: every 2 weeks
The changes in the adipokine levels
The changes in the adipokine levels
Measured: every 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2011 (estimated)
- Study startJan 2008
- Primary completionDec 2010
- Study completionDec 2010
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 SchizophreniaStudies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Medical University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Investigators
- Mong-Liang Lu, Principal investigator, Taipei Medical University-Wan Fang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01401491
- Sponsor's protocol ID
- 95019
- Status last verified
- Jul 2011
- First submitted
- 19 May 2011
- Last updated
- 25 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Lu ML, Chen TT, Kuo PH, Hsu CC, Chen CH. Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study. Schizophr Res. 2018 Mar;193:126-133. doi: 10.1016/j.schres.2017.06.030. Epub 2017 Jul 6.
PubMed 28688742
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Strategy for Refractory Schizophrenia: Drug Interaction Between Clozapine and Fluvoxamine
- ClinicalTrials.gov ID
- NCT01401491
- Acronym / sponsor ID
- 95019
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, clozapine, fluvoxamine, metabolic syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Taipei Medical University HospitalUniversity, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Study start
- Jan 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 25 Jul 2011 (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.
Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. There are patients who do not respond to clozapine, and the need to treat these severely ill patients frequently compels clinicians to adopt therapeutic innovations that lack a sound empirical basis. One strategy is the combination of various other somatic treatments with clozapine.
Recently, the investigators conduct a preliminary open trial to evaluate the safety and efficacy of fluvoxamine coadministration with clozapine in refractory schizophrenic patients. The combined treatment is well tolerated, and clinical improvement is observed in our patients. And the concomitant fluvoxamine could attenuate the clozapine-induced weight gain and metabolic disturbance. However, the effects of fluvoxamine on the safety and therapeutic efficacy of clozapine need to be further clarified in double-blind study.
Detailed description
Background Schizophrenia is one of the most severe mental illnesses. The prevalence of schizophrenia has been variously reported as ranging from 1 to 1.5 percent. More than 50% of patients can be described as having a poor outcome, with repeated hospitalizations, exacerbations of symptoms, episodes of major mood disorders, and suicide attempts. Schizophrenia is costly in medical care, treatment and rehabilitation, and reduced or lost productivity. Therefore, the development of effective treatment for schizophrenic patients is an important issue.
The classical antipsychotic drugs are the dopamine receptor antagonists, which are effective in the treatment of schizophrenia, particularly of the positive symptoms. Even with treatment of typical antipsychotics, about 50% of schizophrenic patients lead severely debilitated lives. Second, the classical antipsychotic drugs are associated with annoying and serious adverse effects. Clozapine has been virtually the only psychopharmacological choice in patients with schizophrenia who either did not response to typical neuroleptics or experienced severe extrapyramidal side effects and consequently did not tolerate this medication. There are patients who do not respond to clozapine, and the need to treat these severely ill patients frequently compels clinicians to adopt therapeutic innovations that lack a sound empirical basis. One strategy is the combination of various other somatic treatments with clozapine.
Recently, the investigators conduct a preliminary open trial to evaluate the safety and efficacy of fluvoxamine coadministration with clozapine in refractory schizophrenic patients. The mean plasma clozapine levels obtained by clozapine 100 mg/day plus fluvoxamine 50 mg/day is close to that produced by 300-mg/day clozapine monotherapy in one of our previous studies. The combined treatment is well tolerated, and clinical improvement is observed in our patients. And the concomitant fluvoxamine could attenuate the clozapine-induced weight gain and metabolic disturbance. However, the effects of fluvoxamine on the safety and therapeutic efficacy of clozapine need to be further clarified in double-blind study.
Methods This study is a three-year proposal. Sixty treatment-resistant schizophrenic inpatients will participate in this project. The subjects will be randomized to one of two parallel groups: clozapine monotherapy and clozapine plus fluvoxamine treatment. The double-blind active treatment will consist of two periods.
The measures of clinical efficacy will be the Positive And Negative Syndrome Scale, Clinical Global Impression, and Nurses'Observation Scale for Inpatient Evaluation. The measures of side effects will be the Extrapyramidal Symptom Rating Scale and the UKU Side Effect Rating Scale. Fasting serum samples are collected to determine the lipid profile (total cholesterol, triglycerides, HDL, and LDL), glucose level, and insulin level. Plasma levels of clozapine, norclozapine, and clozapine N-oxide will be determined by high performance liquid chromatography with ultraviolet detection.
The following results are expected:
- In treatment-resistant schizophrenic patients, global antipsychotic effect of clozapine plus fluvoxamine treatment is superior to clozapine monotherapy.
- Clozapine plus fluvoxamine treatment has less adverse effects than clozapine monotherapy.
- The effect of clozapine plus fluvoxamine treatment on body weight and metabolic disturbances is superior to clozapine monotherapy.
- Steady-state plasma levels of clozapine and its metabolites account for a proportion of variance of clinical effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| clozapine + fluvoxamine | Active comparator | Drug: clozapine plus fluvoxamine |
| clozapine + placebo | Placebo comparator | Drug: clozapine plus placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Inpatients meet the DSM-IV criteria for schizophrenia.
- Treatment refractoriness: Failed to respond to at least two typical neuroleptics at dosage equivalent to or greater than 1000 mg/day of chlorpromazine for a period of at least six weeks.
- Age 18-60 years.
- Males or females.
- Total PANSS score >60
Key exclusion criteria (5 listed)
- History of illicit substance abuse or dependence
- History of clozapine intolerance (such as clinically significant leukopenia or agranulocytosis).
- Patients with WBC count less than 3500/mm3 or ANC count less than 2000/mm3will not be included.
- Any depot neuroleptics within 30 days before the day of randomization.
- Epilepsy, active hepatitis, HIV positivity, or current myeloproliferative disorder. Other medical illnesses may necessitate subjects' exclusion after evaluation of individual cases by the principal investigator and other staffs. Clinical judgment will be used.
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 |
|---|---|---|
| clozapine plus fluvoxamineclozapine 100 mg/day plus fluvoxamine 50 mg/day | Drug | clozapine + fluvoxamine |
| clozapine plus placeboclozapine 300 mg/day plus placebo | Drug | clozapine + placebo |
Primary outcome
the changes in the psychopathology during the trial
Time frame: every 2 weeks
The changes in the scores of psychopathology assessment (the Positive and Negative Syndrome Scale, PANSS)
the changes in the metabolic syndrome parameters during the trial
Time frame: every 2 weeks
The changes in the metabolic syndrome parameters
4 secondary outcomes
the changes in the plasma drug levels
Time frame: every 2 weeks
The changes in insulin levels
Time frame: every 2 weeks
The changes in the depression severity
Time frame: every 2 weeks
The changes in the adipokine levels
Time frame: every 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2011.
- Derived from this study: PubMed 28688742Lu ML, Chen TT, Kuo PH, Hsu CC, Chen CH. Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study. Schizophr Res. 2018 Mar;193:126-133. doi: 10.1016/j.schres.2017.06.030. Epub 2017 Jul 6.
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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.
Mong-Liang Lu principal investigator
Taipei Medical University-Wan Fang Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing clozapine plus fluvoxamine in people with Schizophrenia, run by Taipei Medical University Hospital at 1 site in Taiwan.
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 7 inclusion and 5 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 25 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
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?
the changes in the psychopathology during the trial (time frame: every 2 weeks). 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 NCT01401491, 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 25 Jul 2011.