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NCT Number: NCT02639702

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. However, to date, several randomized controlled trials (RCTs) have shown no differences in clinical outcomes between once- and twice-daily dosing of various antipsychotics, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life. This would apply to clozapine as well; however, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

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Key information

Conditions

Schizophrenia Mental Disorders Psychotic Disorders Schizoaffective Disorder Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location status: Recruiting

Location contact

Gary Remington, MD, PhD

CONTACT

[email protected]

416-535-8501 ext. 34864

Gary Remington, MD, PhD

PRINCIPAL_INVESTIGATOR

Hiroyoshi Takeuchi, MD, PhD

SUB_INVESTIGATOR

Ofer Agid, MD

SUB_INVESTIGATOR

About this study

Plasma half-life has routinely been used to establish the dosing schedule of antipsychotics; for example, it is recommended that agents with a short plasma half-life be administered multiple times per day. To date, however, several randomized controlled trials (RCTs) have shown that once-daily dosing of antipsychotics including perphenazine, risperidone, olanzapine, quetiapine, and asenapine is comparable to twice-daily dosing in terms of efficacy and tolerability, suggesting that once-daily dosing of antipsychotics is a viable option regardless of plasma half-life.

This issue applies to clozapine as well, in that it has a relatively short plasma half-life of 12-16 hours; of note, the product monographs recommends that clozapine be administered more than once daily if the dose exceeds 200 mg/day in Canada. Despite this, in clinical practice clozapine is frequently administered once daily because of convenience and side effects such as a daytime sedation or somnolence, In support of this, a cross-sectional survey done at the investigators' own centre has revealed that clozapine was prescribed once daily in 75.1% of 676 patients, even though >200 mg/day was administered in 88.6%. However, there have been no studies comparing once-daily vs. twice-daily dosing regimens of clozapine in terms of efficacy and tolerability. To address this gap in the literature, the investigators shall conduct a pilot, double-blind, RCT to examine efficacy and tolerability following a switch to once-daily dosing regimen of clozapine in patients with schizophrenia receiving clozapine twice a day.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosed with schizophrenia or schizoaffective disorder based on DSM-IV criteria
  • Outpatient status
  • Ages 18 years or older
  • Has received clozapine twice a day, one of which is in the evening/bedtime, at the same dose and dosing regimen for at least 3 months
  • Fluent in English and competent to provide written informed consent

Exclusion criteria

  • Having significant medical or neurological illnesses
  • Pregnant or lactating

Treatment and study plan

Clozapine

Drug

Switching from twice-daily to once-daily clozapine dosing regimen

Other names: Clozaril

Primary outcomes

  1. Brief Psychiatric Rating 18 item Scale (BPRS 18 item scale)

    Time frame: 0 and 12 weeks

    Change in BPRS total scores from baseline to 12 weeks

    Total scores range from 18-126, higher scores represent worse clinical outcomes:

    <31 = Illness not significant >=31 = Mildly ill >41 = Moderately ill >53 = Markedly ill.

Secondary outcomes

  1. Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C)

    Time frame: 0 and 12 weeks

    Detect side effects related to Clozapine from baseline to 12 weeks

    Higher Scores indicating worse side-effects:

    0-16 (absent/mild side-effects) 17-32 (moderate side-effects) 33-48 (severe side-effects)

  2. Brief Evaluation of Psychosis Symptom Domains (BE-PSD)

    Time frame: 0 and 12 weeks

    Assess the overall severity of five symptom domains of BE-PSD with a total score in each domain scoring from absent to very severe (i.e. 0-6 with higher scores with worse outcomes)

  3. Personal and Social Performance scale (PSP)

    Time frame: 0 and 12 weeks

    Change in patients social functioning scores from baseline to 12 weeks The PSP is a 100-point single item rating scale from 1-100, subdivided into 10 equal intervals with higher scores indicating better outcomes. The ratings are based on patient's functioning in four main areas: 1) socially useful activities, 2) personal and social relationships, 3) self-care; and 4) disturbing and aggressive behaviours.

  4. Clinical Global Impression - Severity of Illness (CGI-S)

    Time frame: 0 and 12 weeks

    Assess severity of Illness in Schizophrenia CGI scores from baseline to 12 weeks Scores ranging from normal to the most ill (i.e., scores ranging from 1-7 with higher scores with illness worsening)

  5. Brief Neurocognitive Assessment (BNA)

    Time frame: 0 and 12 weeks

    The BNA is a brief neurocognitive assessment that measures global cognitive impairment in patients with schizophrenia from baseline to 12 weeks. Negative Z scores (i.e., -0.5 to -2.0 ) indicate mild to severe cognitive impairment.

  6. Subjective Well-being under Neuroleptics scale - Short form (SWNS)

    Time frame: 0 and 12 weeks

    Self report scale to measure well being. Study assess changes in subjective wellbeing in patients on a neuroleptic from baseline to Week 12. Higher total score indicating better outcomes

  7. Change in the Visual Analogue Scale for Distress Associated with Symptoms (VAS-DAS) scores from baseline to 12 weeks

    Time frame: 0 and 12 weeks

    Assess changes in level of distress associated with symptoms from no distress to worst distress (i.e., 0-100)

Study contacts

Contact information is provided by the study sponsor or research team.

Carol Borlido, BSc

CONTACT

[email protected]

416 535-8501 ext. 34321

Gary Remington, MD, PhD

CONTACT

[email protected]

+1-416-535-8501 ext. 34750

Sponsors and collaborators

Lead sponsor

Centre for Addiction and Mental Health

Other

Registry information

Official study title

Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia: A Pilot, Double-Blind, Randomized Controlled Trial

Important dates

Study start
2016
Primary completion
2026
Study completion
2026
First posted
Dec 24, 2015
Registry last updated
Sep 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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