Clozapine induced hypersalivation (CIH) Mental and Behavioural Disorders
Conditions
Interventions
Participants will be randomised via a secure (24-hour) web-based randomisation system controlled centrally by the LCTC to receive either hyoscine hydrobromide, glycopyrronium bromide (glycopyrrolate)
Sponsors
University of Liverpool
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 65 years inclusive. 2. English speaking. 3. Prescribed clozapine for a minimum of three months. 4. Experiencing hypersalivation with a minimum score of 4 on the Drooling Rating Scale (DRS) and are either: 4.1. Currently not receiving treatment for CIH, OR 4.2. Receiving drug treatment for CIH and agreeable to a 48-hour washout period 5. Written and informed consent obtained from participant (with capacity and ability) and agreement of participant to comply with the requirements of the trial prior to study specific procedures.
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 27/05/2026: 1. Medical conditions that could influence hypersalivation (e.g., Parkinson’s Disease). 2. Neurological conditions that could affect cognitive functioning during the course of the study (e.g., unstable epilepsy). 3. History of an allergic reaction to hyoscine hydrobromide 4. History of an allergic reaction to glycopyrrolate. 5. Any of the following contra-indications to hyoscine hydrobromide or glycopyrrolate as stated in the British National Formulary: 5.1. Prostatic enlargement 5.2. Myasthenia gravis 5.3. Pyloric stenosis 5.4. Paralytic ileus 5.5. Glaucoma 5.6. Hepatic Impairment 6. Any of the following cautions to hyoscine hydrobromide or glycopyrrolate as stated in the British National Formulary: 6.1. Chronic heart failure 6.2. Stomach ulcer 6.3. Ulcerative colitis 6.4. Significant liver disease that in the opinion of the CI or PI is a contraindication 6.5. Down’s syndrome 6.6. Arrhythmia and/or history of myocardial infarction 6.7. Overactive thyroid gland. 6.8. Unstable angina 7. Current prescription for potassium chloride, digoxin, amantadine, levodopa, tricyclic antidepressants or monoamine oxidase inhibitors 8. Pregnant, trying to conceive or breastfeeding. 9. Participation in another drug study within the preceding 12 weeks (or within 5 half-lives of an IMP, whichever is longer) or use of other investigational drugs. 10. Active suicidal ideation as assessed within usual care. 11. Known sensitivity to any interventions or excipients. 12. Known history of intestinal obstruction. 13. Known history of urinary retention. 14. Severe renal impairment (eGFR <30 ml/min/1.73m2). 15. Known history of brain tumour or encephalitis. 16. Any contraindication to dispensing monthly supply of medications. 17. Unable to swallow tablets. Previous participant exclusion criteria as of 07/03/2024: 1. Medical conditions that could influence hypersalivation (e.g., Parkinson’s Disease). 2. Neurological conditions that could affect cognitive functioning during the course of the study (e.g., unstable epilepsy). 3. History of an allergic reaction to hyoscine hydrobromide 4. History of an allergic reaction to glycopyrrolate. 5. Any of the following contra-indications to hyoscine hydrobromide or glycopyrrolate as stated in the British National Formulary: 5.1. Prostatic enlargement 5.2. Myasthenia gravis 5.3. Pyloric stenosis 5.4. Paralytic ileus 5.5. Glaucoma 5.6. Hepatic Impairment 6. Any of the following cautions to hyoscine hydrobromide or glycopyrrolate as stated in the British National Formulary: 6.1. Chronic heart failure 6.2. Stomach ulcer 6.3. Ulcerative colitis 6.4. Significant liver disease that in the opinion of the CI or PI is a contraindication 6.5. Down’s syndrome 6.6. Arrhythmia and/or history of myocardial infarction 6.7. Overactive thyroid gland. 6.8. Unstable angina 7. Current prescription for potassium chloride, digoxin, amantadine, levodopa, tricyclic antidepressants or monoamine oxidase inhibitors 8. Pregnant, trying to conceive or breastfeeding. 9. Sexually active heterosexual patients who are unable or unwilling to use contraception during the study (see section 10.4). 10. Participation in another drug study within the preceding 12 weeks (or within 5 half-lives of an IMP, whichever is longer) or use of other investigational drugs. 11. Active suicidal ideation as assessed within usual care. 12. Known sensitivity to any interventions or excipients. 13. Known history of i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome as of 27/05/2026: Hypersalivation measured using the Drooling Rating Scale at Baseline, T 1, 2, 4, 6, 8, 12 Previous primary outcome: Hypersalivation measured using the Drooling Rating Scale at Baseline, T 1, 2, 4, 6, 8, 12 and Optional T16, 20, 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Neuroleptic side-effects measured using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) PROM (participant reported outcome measure) at Baseline, T 4, 8, 12 and Optional T16, 20, 24 2. Anticholinergic side effects measured using the Liverpool Anticholinergic Side-effects Scale (LASS) PROM at Baseline, T 4, 8, 12 and Optional T16, 20, 24 3. Sustained attention and Verbal Recognition Memory (VRM) measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a pre-loaded tablet device at Baseline and T12 4. Nocturnal hypersalivation measured using the Nocturnal Hypersalivation Rating Scale (NHRS) PROM at Baseline, T 1, 2, 4, 6, 8, 12 and Optional T16, 20, 24 5. Self-esteem measured using the Rosenberg Self-esteem scale (RSE) PROM at Baseline and T12 6. Hospital admission (whether for physical or psychiatric reasons) from Consent up to T12 and Optional follow-up to T24 7. Constipation measured using the Patient assessment of constipation and symptoms (PAC-SYM) at Baseline, T4, 8, 12 and Optional T24 8. Social functioning measured using the Personal and Social Performance scale (PSP) conducted via interview at Baseline and T12 9. Symptoms of schizophrenia measured using the Positive and negative syndrome scale (PANSS) conducted via interview at Baseline and T12 10. Effect and tolerability of treatment measured by premature discontinuation of study treatment/Continuation at T12 11. Discontinuation of clozapine 12. Serious Adverse Events reported from Consent up to T12 and Optional follow-up to T24 Updated 01/05/2024: Exploratory outcome measure: 1. Clozapine plasma levels from blood analysis at Baseline and T12 (moved from secondary outcome measures) | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactJulie Perry
Outcome results
None listed