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Completed

NCT Number: NCT03510325

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments(SMART-CAT)

This study is a sequential multiple-assignment randomized trial (RCT) of antipsychotic medication treatment in first-episode schizophrenia patients in the real-world settings.Through analysis of treatment efficacy rate and adverse reactions and pharmacoeconomic evaluation, this project intends to provide evidence for the selection of antipsychotics in FES patients as well as the efficacy and safety of using clozapine in the early phase of schizophrenia treatment by comparing with other SGAs.

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

16 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Beijing Anding Hospital of Capital Medical University, Beijing, Beijing Municipality, China

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About this study

A total of 720 first-episode schizophrenia (FES) patients will be enrolled and followed up for 12 months in this study. The trial includes three treatment phases (each phase lasting for 8 weeks) and a naturalistic follow-up phase. Phase 1 is a 8-week randomized controlled trial; patients will be randomly assigned to one of the treatments with oral olanzapine, risperidone, amisulpride, aripiprazole or perphenazine. Patients who had an acceptable response to the randomly assigned drug therapy will remain on that treatment for a 12-month treatment period. Subjects who fail to respond in phase 1 will switch to phase 2, an equipoise-stratified randomization trial, in which patients will be randomly assigned to oral olanzapine, amisulpride or clozapine for another 8 weeks. No-responders in phase 2 will further enter an open label trial (phase 3). Patients who receive clozapine in phase 2 will be assigned to an extended clozapine treatment or modified electroconvulsive therapy add-on therapy (Phase 3A). Patients who were not assigned to clozapine in phase 2 will be assigned to treatment with clozapine or another SGAs not previously used in phase 1 and 2 (Phase 3B).

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Patients must meet the DSM-5 diagnostic criteria for schizophrenia , schizophreniform disorder or schizoaffective disorder, based upon the structured clinical interview by research psychiatrist using Mini International Neuropsychiatric Interview 7.0 (M.I.N.I. 7.0), review of their clinical records, and input from available informants.
  • Inpatients or outpatients.
  • 16-45 years of age.
  • First episode, and the course no more than 3 years.
  • Drug-naïve, or any antipsychotic medication had been used no more than 2 weeks, and the cumulative antipsychotic drug exposure time no more than 6 weeks in lifetime.
  • The severity of psychotic symptoms is moderate or above, and the specific criteria including: have a score ≥4 on at least one item of Positive and Negative Syndrome Scale (PANSS) (delusions, conceptual disorganization, hallucinatory behavior, grandiosity, or suspiciousness/persecution), and PANSS total score >70.
  • Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide informed consent to participate.

Exclusion criteria

  • Patients were excluded if more than 3 years had passed since the onset of psychosis;
  • They met any of the contraindications for any of the study drugs;
  • Mental symptoms were caused by organic disease, severe physical illness, psychoactive substance dependence, mental retardation;
  • They were pregnancy or breast-feeding; they were extreme agitation, stupor or negative suicide.

Treatment and study plan

Phase 1: Olanzapine

Drug

Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks

Phase 1: Risperidone

Drug

Initial dosage: 1-2 mg; recommended dosage: 2-6 mg/d; dosage form: po. duration: 8 weeks

Phase 1: Amisulpride

Drug

Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks

Phase 1: Aripiprazole

Drug

Initial dosage: 5-10 mg; recommended dosage: 10-30 mg/d; dosage form: po. duration: 8 weeks

Phase 1: Perphenazine

Drug

Initial dosage: 2-4 mg; recommended dosage: 6-36 mg/d; dosage form: po. duration: 8 weeks

Phase 2: Olanzapine

Drug

Initial dosage: 5-10 mg; recommended dosage: 5-20 mg/d; dosage form: po. duration: 8 weeks

Phase 2: Amisulpride

Drug

Initial dosage: 200-400 mg; recommended dosage: 400-1200 mg/d; dosage form: po. duration: 8 weeks

Phase 2: Clozapine

Drug

Initial dosage: 25-50 mg; recommended dosage: 200-400 mg/d; dosage form: po. duration: 8 weeks

Phase 3A: Clozapine extended treatment or Combined clozapine-MECT therapy

Other

Clozapine extended treatment:

dosage: 200-600 mg/d; dosage form: po.

Combined clozapine-MECT therapy:

Dosage of clozapine: 200-600 mg/d; The modified electroconvulsive therapy (MECT) will be administered three times per week for the first 2 weeks, then twice a week for the next 2 weeks. The total treatment duration is about one month.

Phase 3B: Clozapine or another SGAs

Drug

Clozapine:

Initial dosage: 25-50 mg; recommended dosage: 200-600 mg/d; duration: 8 weeks

Another Second generation antipsychotics (SGAs) (not previously used in phase 1 and 2): Olanzapine, risperidone, amisulpride, or aripiprazole The dosage of each drug is the same as that of phase 1 and phase 2.

Primary outcomes

  1. Treatment efficacy rate

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    A 40% reduction or more of the total score in the Positive and Negative Syndrome Scale (PANSS). The PANSS scale consists of 30 items, and each item is rated on a 7-point scale, ranging from 1 (no symptoms) to 7 (extremely severe).

  2. All-cause dropout rate

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Marked by the treatment discontinuation for any reasons, including poor efficacy, intolerance of adverse reactions, poor compliance and other reasons.

Secondary outcomes

  1. Change from baseline in Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Clinician-Rated Dimensions of Psychosis Symptom severity (CRDPS). The CRDPS scale evaluates eight symptom dimensions of psychosis. Each symptom domain is rated for the past 7 days on a 5-point scale ranging from 0 (absent) to 4 (present and severe).

  2. Cost inventory

    Time frame: baseline,2 months,4 months, 6 months and 12 months

    Direct medical costs (for example, antipsychotics costs, medical examinations costs, health care and service costs and adverse events costs) and indirect costs (such as traffic, nursing, and losing of labor) of the treatments.

  3. Change from baseline in Clinical Global Impression Scale-Severity (CGI-S)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Clinical Global Impression Scale-Severity (CGI-S), including assessment of disease severity and overall efficacy. The severity of the disease was scored on an eight-point scale ranging from 0 (not rated) to 7 (extremely severe). The overall efficacy was assessed on an 8-point scale ranging from 0 (not assessed) to 7 (significant deterioration).

  4. Change from baseline in Calgary Depression Scale for Schizophrenia (CDSS)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    The Calgary Depression Scale for Schizophrenia (CDSS) consists of nine items, each scored from 0 to 3. A total score greater than 6 is considered depression.

  5. Social function

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Chinese version of UPSA-B, the UCSD (University of California,San Diego) Performance-based Skills Assessment-Brief, consists of two parts: financial skill (A and B) and communication skill. The score of financial skill A range from 0 to 5. The score of financial skill B range from 0 to 6. The score of communication skill range from 0 to 9. The higher scores mean a better outcome.

  6. Life quality: The Heinirich Quality of life Scale (HRQOL)

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    The Heinirich Quality of life Scale (HRQOL) consists of 21 items, each scored from 0 to 6. The higher scores mean a better outcome.

  7. Life quality: Medication Satisfaction Questionnaire (MSN)

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Medication Satisfaction Questionnaire (MSN) has one item, scored from 1 to 7. The higher scores indicate higher satisfaction with the medication.

  8. Life quality: Subjective Well-being under Neuroleptics (SWN)

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Subjective Well-being under Neuroleptics (SWN) consists of 20 items, each scored from 1-6.

  9. Extrapyramidal adverse effects: The Barnes Akathisia Scale (BAS)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    The Barnes Akathisia Scale (BAS) will be used to evaluate objective performance and subjective experience of akathisia, scored from 0 to 3, and the overall clinical evaluation of akathisia is scored from 0 to 5. The higher scores mean a more serious side effect.

  10. Extrapyramidal adverse effects: Simpson-Angus Extrapyramidal Side Effects Scale (SAS)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Simpson-Angus Extrapyramidal Side Effects Scale (SAS) consists of 10 items, each scored from 0 to 4. The higher scores mean a more serious side effect.

  11. Extrapyramidal adverse effects: Abnormal Involuntary Movement Scale (AIMS)

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Abnormal Involuntary Movement Scale (AIMS) consists of 12 items. The first 10 of 12 items is scored from 0 to 4, and the last 2 is scored from 0 to 1. The higher scores mean the more obvious abnormal involuntary movement.

  12. Sexual dysfunction

    Time frame: baseline,0.5 months,1 months, 2 months,4 months , 6 months , 8 months and 12 months

    Arizona Sexual Experiences Scale (ASEX) includes 5 items, each scored from 1-6. A total score greater than or equal to 19 and any item greater than or equal to 5, or any 3 items greater than or equal to 4, can help clinical diagnosis of sexual dysfunction.

  13. Change from baseline in cognitive function: MCCB

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    MATRICS consensus cognitive battery (MCCB) consists of 10 tests that assess cognitive performance in 7 domains, including processing speed, attention/vigilance, working memory, verbal memory, visual learning, reasoning and problem solving, and social cognition.

  14. Change from baseline in cognitive function: NBSC

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    New cognitive battery for patients with schizophrenia in China(NBSC). NBSC includes 4 tests from MCCB and 5 new tests (Trial making A, BACS, HVLT-R learning and recall, CPTIP, dominant hand Grooved Pegboard, Color Trails I and II, PASAT)

  15. Safety index: Blood pressure

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Blood pressure in mmHg

  16. Safety index: Heart rate

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Heart rate

  17. Safety index: Respiratory rate

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    respiratory rate

  18. Safety index: Vital signs

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    body temperature in celsius

  19. Safety index: Blood count

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Blood count

  20. Safety index: Liver function

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    *Concentration of ALT, AST, GGT, ALP, TB, and DB.

  21. Safety index: renal function

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    *Concentration of serum creatinine, blood urea nitrogen, uric acid, serum cystatin C, homocysteine.

  22. Safety index: thyroid function

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Thyroid function related hormone levels will be tested, including FT3, FT4, T3, TSH, and T4.

  23. Safety index: prolactin

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Serum prolactin level

  24. Safety index: QTc interval

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    QTc interval

  25. Metabolic side effects: body weight

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Weight in kilograms

  26. Metabolic side effects: BMI

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    BMI in kg/m^2

  27. Metabolic side effects: waist circumstance

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Waist circumstance in centimeter

  28. Metabolic side effects: fasting blood-glucose

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Fasting blood-glucose

  29. Metabolic side effects: insulin index

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Insulin resistance was assessed using homeostasis model assessment (HOMA-IR).

  30. Metabolic side effects: serum lipid level

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Concentration of serum triglyceride, LDL-C(low density lipoprotein cholesterol), HDL-C(high density lipoprotein cholesterol) and apolipoprotein.

  31. Metabolic side effects: assessment of feeding behavior

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Three-Factor Eating Questionnaire (TFEQ-21) consists of 21 items, including 3 dimensions (non-controlled eating, cognitively restricted eating, and emotional eating). Each item is scored from 1 to 4, and the first 16 item requires reverse scoring before calculating dimension scores. The higher scores mean a higher tendency for non-controlled eating, cognitively restricted eating, and emotional eating.

  32. Metabolic side effects: Visual Analogue Scale (VAS)

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Visual Analogue Scale (VAS) was used to evaluate the desire to eat, hunger sensation and willingness to eat. The scale consists of 3 items, each scored from 0 to 10. The higher scores mean a stronger desire to eat, hunger sensation and willingness to eat.

  33. Metabolic side effects: Physical Activity Evaluation

    Time frame: baseline,2 months,4 months and 6 months and 12 months

    Physical Activity Evaluation

  34. MRI examinaitons

    Time frame: baseline,2 months and 4 months

    Change of grey matter volume and functional connectivity in certain brain region was focused in the MRI examinations, to evaluate the ability of MRI examinaitons (structural MRI, functional MRI and Magnetic Resonance Spectroscopy) to predict response to antipsychotic treatment in first-episode schizophrenia.

  35. Pharmacogenomics

    Time frame: baseline,2 months,4 months

    *Blood sample was collected and genes related to drug efficacy and adverse reaction were tested to evaluate the ability of pharmacogenomics to predict response to antipsychotic treatment in first-episode schizophrenia.

  36. Lipidomics

    Time frame: baseline,2 months,4 months

    *Serum sample was collected for lipidomic analysis to investigate correlation between serum lipids and rapid weight gain in first-episode schizophrenia.

Sponsors and collaborators

Lead sponsor

Shanghai Mental Health Center

Other

Registry information

Official study title

Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Apr 27, 2018
Registry last updated
Apr 8, 2025

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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