Patients with severe insomnia which is interfering with normal daily life, and where other sleep therapies (behavioural and pharmacologic) have failed. Nervous System Diseases
Conditions
Interventions
The trial will have one treatment arm, where all trial participants will receive Chloral Hydrate oral solution daily for up to 2 weeks. Chloral Hydrate is licensed in the UK, for the short-term treatm
Sponsors
Pharmanovia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged =18 years and =75 years 2. Participant is willing and able to give informed consent 3. Clinically significant impairment from severe insomnia (eg. ISI score 22-28) 4. Previous treatment with sleep therapies (behavioural and pharmacologic), which have failed. Defined as the presence of ongoing severe insomnia (ISI score 22-28), despite previous use of other sleep therapies. 5. Able to adhere to study procedures 6. Willingness to take a pregnancy test prior to starting IMP treatment (participants of childbearing potential)
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding 2. Taking any substances that significantly affect sleep during the 2 week IMP treatment period 3. Starting any new behavioural sleep therapies* during the 2 week IMP treatment period 4. At point of enrolment taking substances that affects sleep at greater than maximum licensed doses 5. Other sleep diagnosed/suspected sleep disorders (restless legs, periodic limb movements, unusual sleep timings (indicative of advanced/delayed sleep, etc), parasomnias 6. Known severe hepatic impairment 7. Known moderate / severe renal impairment / eGFR <60 8. Known severe sleep apnea 9. Known severe cardiac disease 10. Known cardiac disease with QT prolongation 11. History of myocardial infarction in the last 12 months 12. History of stroke or TIA 13. Taking medication that may cause QT prolongation 14. Active gastritis, oesophagitis, gastric or duodenal ulcers or perforation 15. Susceptible to acute attacks of porphyria 16. Hypersensitivity to chloral hydrate or to any of the excipients (glycerol, liquid glucose, citric acid, sodium citrate, sodium benzoate, saccharin sodium, essence of passion fruit [containing natural flavouring, artificial flavouring, propylene glycol], and purified water) 17. Individuals with a history of alcohol or drug abuse or dependence 18. Patients taking antipsychotic medication in last 12 months 19. History of overdose or attempted overdose 20. History of significant psychiatric disease 21. Patients are taking one of the drugs listed as interacting with Chloral Hydrate and would need to continue taking these during the trial: alcohol, CNS depressants, antipsychotics, hypnotics, anxiolytics/sedatives, antidepressant agents, centrally acting muscle relaxants, narcotic, analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines, intravenous furosemide, anticoagulants. 22. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 23. Participants who have participated in another research trial involving an investigational product in the past 4 months 24. Participants of childbearing potential (participants who are anatomically and physiologically capable of becoming pregnant), or have a partner of childbearing potential, not willing to use highly effective contraceptives** for the duration of the trial, and who do not confirm a negative pregnancy test prior to starting the drug. *Participants currently undergoing behavioural sleep therapies, such as CBT, will continue on these during the trial, in line with the licensing for chloral hydrate licensing, where chloral hydrate should be used as an adjunct to behavioural therapies. However, they should not start any new behavioural sleep therapies during the 2 week IMP treatment period. **Highly effective methods have typical-use failure rates of less than 1% and include sterilisation and long-acting reversible contraceptive (LARC) methods (intrauterine devices and implants) OR if a couple are using another method of contraception, such as a combined hormonal method, progestogen only pill or injection, they are only eligible if they are willing to use an additional barrier method (e.g. male condom) for the 28-day duration of follow-up in the trial. Note: a barrier method on its own is not sufficient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in self-rated insomnia severity, assessed using the Insomnia Severity Index at baseline and 2 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in self-rated insomnia severity, assessed using the Insomnia Severity Index at Baseline, 1 and 6 weeks 2. Change in Epworth Sleepiness Scale (ESS) scores at Baseline, 1, 2 and 6 weeks 3. Change in health-related quality of life, measured using the ShortForm 36 Questionnaire (SF-36) and EQ-5D-5L at Baseline, 1, 2 and 6 weeks 4. Change in subjective sleep measured using the NHS sleep diary over 7 days, at baseline, 1, 2, 3 and 6 weeks 5. Change in Hospital Anxiety and Depression Scale (HADS) scores at Baseline, 1, 2 and 6 weeks 6. Change in Pittsburgh Sleep Quality Index (PSQI) scores at Baseline, 2 and 6 weeks 7. Evaluation of overall safety of chloral hydrate by the monitoring of AEs and SAEs over 6 week trial duration 8. Daily intervention adherence for the duration of the intervention (Days 1-14) 9. Number of participants withdrawn from the IMP due to an AE, during the 2 week treatment period 10. Change in use of non-pharmacological sleep therapies at Baseline, 1, 2 and 6 weeks 11. Change in: - Concomitant medication at Baseline, 1, 2 and 6 weeks - Over the counter medication used to facilitate sleep at Baseline, 1, 2 and 6 weeks 12. Clinical Global Impressions - Severity Scale (CGI-S) assessed at baseline, and Clinical Global Impressions – Improvement scale (CGI-I) assessed after IMP treatment by the medically qualified doctor at baseline, and CGI-I at 2 and 6 weeks Exploratory end point 13. Change in percentage of days off work at 1 month and 12 months prior to baseline, and 2 and 6 weeks | — |
Countries
United Kingdom
Outcome results
None listed