Valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia

JRCT ID: jRCTs031200338

Registered date:02/02/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Schizophrenia
• Date of first enrollment: 28/02/2023
• Target sample size: 170
• Study type: Interventional

Intervention(s)

6-week drug treatment period (Week0 to week6)
(1) lurasidone group
According to the patient allocation, 40 mg of lurasidone hydrochloride is administered orally once daily after meal. The dosage may be adjusted according to the patient's age and symptoms, but the daily dose should not exceed 80 mg.
The tapering of primary antipsychotic drug is started with the prescription of lurasidone as a principle, and the switching to lurasidone is started. The primary antipsychotic drug is gradually decreased and stopped within 4 weeks, while checking patient status. The dose should not be changed as much as possible during the first 4 to 6 weeks after starting the study drug.
For antipsychotic drugs other than the primary drug, the patient has been taking the drug for more than 30 days before the informed consent date, and if the administration and dosage are not changed, only one antipsychotic drug can be continued during the participation in this study. However, the total amount of antipsychotic drugs used in concomitant use with lurasidone shall not exceed 1000 mg/day in chlorpromazine (CP) equivalent.
(2) paliperidone group
According to the patient allocation, 6 mg of paliperidone is administered orally once daily after breakfast. The dosage may be adjusted according to the patient's age and symptoms within a range not exceeding 12 mg/day, but the dose should be increased by 3 mg/day at intervals of 5 days or more. The tapering of primary antipsychotic drug is started with the prescription of paliperidone as a principle, and the switching to paliperidone is started. The primary antipsychotic drug is gradually decreased and stopped within 4 weeks, while checking patient status. The dose should not be changed as much as possible during the first 4 to 6 weeks of the study.
For antipsychotic drugs other than the primary drug, the patient has been taking the drug for more than 30 days before the informed consent date, and if the administration and dosage are not changed, only one antipsychotic drug can be continued during the participation in this study. However, the total amount of antipsychotic drugs used in concomitant use with paliperidone shall not exceed 1000 mg/day in chlorpromazine (CP) equivalent.

24 week NEAR treatment period (Week7 to Week30)
(1) luracidone plus NEAR group
Lurasidone and other concomitant medications should be maintained as unchanged as possible from the dosage regimen used during the 6-week drug treatment period. If the physician determines clinically that a dose change is necessary, prescribe according to the lurasidone package insert.
Possible NEAR consists of 2 times a week, each 45 to 60 minutes of cognitive task sessions and a 10-20 minute bridging language session.
(2) paliperidone plus NEAR
Paliperidone and other concomitant medications should be maintained as unchanged as possible during the 6-week drug treatment period. If the physician determines clinically that a dose change is necessary, prescribe according to the paliperidone package insert.
Possible NEAR consists of 2 times a week, each 45 to 60 minutes of cognitive task sessions and a 10-20 minute bridging language session.

Outcome(s)

• Primary Outcome: The amount of change in the BAC App composite T-score from baseline at the end of the 24 weeks NEAR treatment period

Secondary Outcome

The amount of change in PANSS
The amount of change in BNSS
The amount of change in MADRS
The amount of change in BAC App sub-item T-score
The amount of change in UPSA-B
The amount of change in SLOF
The amount of change in SQLS
The amount of change in EuroQol-5D-5L (EQ 5D-5L)
The amount of change in WPAI
The amount of change in DPB
Adverse event
DIEPSS
Vital signs
Height, weight
Laboratory values (hematology and clinical chemistry)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 60age old
• Gender: Both

Include criteria

1) Patients who meet the DSM-5 criteria for schizophrenia
2) Patients who have the capacity to give consent and who are able to give written consent from themselves.
3) Outpatients
4) Male and female patients aged 18-60 years on the date of informed consent
5) Patients who wish to switch to an antipsychotic medication and to whom their physician agrees
6) Patients who are not at risk of self-injury or other injury during the past 6 months from the date of informed consent
7) Patients without acute illness requiring treatment
8) For patients with chronic disease (E.G., hypertension), treatment was continued for 1 month prior to participation and the patient's condition remained stable
9) Patients who can participate in 2 weekly cognitive rehabilitation sessions (Each session lasts approximately 60 to 75 minutes)
10) Patients who can undergo neuropsychological evaluation (BAC App)
11) Patients with an antipsychotic chlorpromazine (CP) equivalent of 1,000 mg/day or less in the past 30 days from the date of informed consent.
12) Patients whose primary antipsychotic type has not changed in the last 30 days from the date of informed consent

Exclude criteria

1) Patients with pre-morbid IQ less than 70 on the JART-25 test
2) Patients with impaired hearing or vision
3) Patients whose native language is not Japanese
4) Patients currently being treated with lurasidone, paliperidone, or clozapine
5) Patients taking three or more antipsychotic drugs
6) Patients with a history of resistance to treatment as evidenced by the fact that over the past 12 months from the date of informed consent, treatment with at least 2 appropriate doses of antipsychotics (dose indicated in the package insert) for at least 6 weeks did not improve the outcome.
7)Patients under treatment with psychotropic drugs known to affect cognitive function such as methamphetamine etc.
8)Patients who have received an antipsychotic sustained-release injection in the past 6 weeks from the date consent was obtained.
9)Patients with a history of electroconvulsive therapy (ECT) during the past 6 months from the date of informed consent, or patients with a history of potential need for ECT during the study.
10) Patients who are likely to have attempted suicide during this study.
11) Patients with a history of intracranial disease or CNS disease (E.G., stroke, traumatic brain injury, epilepsy, parkinsons disease,etc.).
12) Patients with clinically serious physical disorders
13) Patients with a history of alcohol, drug abuse, or dependence within the past 6 months from the date of consent.
14) Pregnant women or women who wish to become pregnant.
15) Women who are breastfeeding.
16) Patients who have undergone cognitive rehabilitation within 6 months prior to screening test
17) Patients with contraindications to latuda tablets
a) Comatose patient
b) Patients under the strong influence of central nervous system depressants such as barbiturates
c) Patients requiring treatment with a potent CYP3A4 inhibitor (azole antifungals (itraconazole, voriconazole, miconazole (oral agent, oral cavity agent, parenteral ingection), fluconazole, fosfluconazole, posaconazole), HIV protease inhibitors (ritonavir, lopinavir/ritonavir, nelfinavir, darunavir, atazanavir, fosamprenavir), preparations containing cobicistat, clarithromycin, etc.) or a potent CYP3A4 inducer (rifampin, phenytoin, etc.).
d) Patients receiving epinephrine (unless epinephrine is used for emergency treatment of anaphylaxis)
e) Patients with a history of hypersensitivity to ingredients of latuda tablets
18) Patients with contraindications to paliperidone products
a) comatose patient
b) Patients under the strong influence of central nervous system depressants such as barbiturates
c) Patients receiving epinephrine (unless epinephrine is used for emergency treatment of anaphylaxis)
d) Patients with a history of hypersensitivity to ingredients of paliperidone and risperidone.
e) Patients with moderate to severe renal impairment (CrCl < 50 mL/min)
19) Patients judged to be inappropriate as research subjects by the investigator and the sub-investigator

Related Information

• Primary Sponsor: Nakagome Kazuyuki
• Secondary Sponsor: Sumitomo Pharma Co., Ltd.