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An Investigator-Initiated Phase II Clinical Trial of a Therapeutic Agent for Clozapine-Induced Sialorrhea

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Clozapine-induced sialorrhea
Date of first enrollment	20/04/2026
Target sample size	30
Countries of recruitment
Study type	Interventional
Intervention(s)	Participants with clozapine-induced sialorrhea will be assigned to one of the following three groups and treated with the investigational product for 15 days. The investigational product will be administered orally at a dose of one capsule four times daily, basically after each meal and before bedtime. [Placebo group] Encapsulated lactose hydrate. [DXM 60 mg group] Each capsule contains 15 mg of dextromethorphan hydrobromide. [DXM 120 mg group] Each capsule contains 30 mg of dextromethorphan hydrobromide

Outcome(s)

Primary Outcome

Change in salivary secretion (g) from pre-dose on Day 1 (start of study drug administration) to post-dose on Day 15 (after 2 weeks of study drug administration).

Secondary Outcome

1) Change in salivary secretion (g) From pre-dose on Day 1 to post-dose on Day 8 and to Day 43. 2) Percent change in salivary secretion (g) From pre-dose on Day 1 to pre-dose and post-dose on Day 8, pre-dose and post-dose on Day 15, and to Day 43. 3) Percent change in salivary secretion (g) From post-dose on Day 1 to post-dose on Day 8, post-dose on Day 15, and to Day 43. 4) Percent change in salivary secretion (g) Between pre-dose and post-dose on Day 1, Day 8, and Day 15. 5) Changes in DSS, DFS, and DSFS scores From Day 1 to Day 8, Day 15, and Day 43. (DSFS score is the sum of DSS and DFS scores). 6) Change in PANSS total score From Day 1 to Day 15 and Day 43. (PANSS total score is the sum of the scores of all evaluation items). 7) Change in NHS From Day 1 to Day 8, Day 15, and Day 43. 8) Change in EQ-5D-5L index value From Day 1 to Day 15 and Day 43. (QOL value calculated using the conversion table). 9) Blood concentration of DXM at each measurement time point

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	<= 65age old
Gender	Both
Include criteria	1. Patients diagnosed with treatment-resistant schizophrenia and currently receiving clozapine treatment. 2. Patients whose clozapine dosage has remained unchanged for at least 28 days prior to obtaining informed consent. 3. Patients presenting with clozapine-induced sialorrhea (CIS) at screening, defined as a Drooling Severity Scale (DSS) score of 3 or higher (Moderate: drool reaches the lips or chin). 4. Patients aged between 18 and 65 years at the time of obtaining informed consent. 5. Patients (or their legally authorized representatives) who have provided written informed consent voluntarily after receiving a full explanation and gaining a thorough understanding of the clinical trial.
Exclude criteria	1. Patients with comorbid diseases of the salivary glands or oral cavity that may affect sialorrhea (e.g., Sjogren's syndrome). 2. Patients with comorbid diseases other than those of the salivary glands or oral cavity that may affect sialorrhea (e.g., Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, sequelae of cerebral infarction, cerebral palsy, sequelae of traumatic brain injury). 3. Patients who have used dextromethorphan (DXM) within 14 days prior to obtaining informed consent. 4. Patients who have used NMDA receptor antagonists within 14 days prior to obtaining informed consent. 5. Patients who have used muscarinic receptor antagonists or alpha 2-receptor agonists within 14 days prior to obtaining informed consent. 6. Patients who have used sigma-1 receptor agonists or antagonists within 14 days prior to obtaining informed consent. 7. Patients who have used serotonergic agents within 14 days prior to obtaining informed consent. 8. Patients who have used NaSSAs, tricyclic antidepressants (TCAs), or tetracyclic antidepressants within 14 days prior to obtaining informed consent. 9. Patients who have received electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within 14 days prior to obtaining informed consent. 10. Patients with a history of substance use disorder within 12 months prior to obtaining informed consent (based on DSM-5-TR criteria). 11. Patients with a history of over-the-counter (OTC) drug overdose (e.g., DXM) within 12 months prior to obtaining informed consent. 12. Patients with a history of hypersensitivity to DXM. 13. Patients with a history of serotonin syndrome. 14. Patients with serious comorbid physical illnesses requiring inpatient treatment, or those judged inappropriate for the study by the investigator or sub-investigator. 15. Patients at risk of suicide based on responses to items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, or those with a suicide attempt within the past 12 months based on response to item 6. 16. Patients who have received other investigational products within 12 weeks prior to the start of study drug administration. 17. Female patients who are pregnant or breastfeeding. For female patients of childbearing potential, those who do not agree to use contraception from the time of informed consent until the end of the observation period. For male patients, those who (or whose partners) do not agree to use contraception from the time of informed consent until the end of the observation period. 18. Other patients judged inappropriate for the safe conduct of the study by the investigator or sub-investigator.