An Open-label Trial to Evaluate the Safety and Efficacy of Chloral Hydrate in Patients with Severe Insomnia (RESTORE)

The primary aim of this Real-World Evidence trial is to establish whether short-term (2 weeks) treatment of Chloral Hydrate is effective in patients with severe insomnia which is interfering with normal daily life, and where other behavioural and pharmacologic therapies have failed in a real world setting.

Study Overview

• Status: Completed
• Conditions: Insomnia; Insomnia Chronic; Chloral Hydrate
• Intervention / Treatment: Drug: Chloral Hydrate

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 3ER
    • Lindus Health, The Leather Market Weston Street, Bermondsey,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years and ≤75 years
• Participant is willing and able to give informed consent
• Clinically significant impairment from severe insomnia (eg. ISI score 22-28)
• 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.
• Able to adhere to trial procedures
• Willingness to take a pregnancy test prior to starting IMP treatment (participants of childbearing potential)

Exclusion Criteria:

• Pregnant or breastfeeding
• Taking any substances that significantly affect sleep during the 2 week IMP treatment period
• Starting any new behavioural sleep therapies* during the 2 week IMP treatment period
• At point of enrolment taking substances that affects sleep at greater than maximum licensed doses
• Other sleep diagnosed/suspected sleep disorders (restless legs, periodic limb movements, unusual sleep timings (indicative of advanced/delayed sleep, etc), parasomnias
• Known severe hepatic impairment
• Known moderate / severe renal impairment / eGFR <60
• Known severe sleep apnea
• Known severe cardiac disease
• Known cardiac disease with QT prolongation
• History of myocardial infarction in the last 12 months
• History of stroke or TIA
• Taking medication that may cause QT prolongation
• Active gastritis, oesophagitis, gastric or duodenal ulcers or perforation
• Susceptible to acute attacks of porphyria
• 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)
• Individuals with a history of alcohol or drug abuse or dependence
• Patients taking antipsychotic medication in last 12 months
• History of overdose or attempted overdose
• History of significant psychiatric disease
• 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.
• 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.
• Participants who have participated in another research trial involving an investigational product in the past 4 months
• 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 IMP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Drug: Chloral Hydrate; Participants will be involved in the trial for approximately 7-8 weeks, the first week to collect baseline data and complete screening and eligibility confirmation, the following two weeks they will administer IMP, and there will be a further 4 week observation period. All trial recruitment and follow-up procedures will be conducted remotely via telephone/video calls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effectiveness of Chloral Hydrate in reducing insomnia severity	Change in self-rated insomnia severity, assessed using the Insomnia Severity Index	Self-rated insomnia severity, assessed at baseline and 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore whether Chloral Hydrate will affect Self-rated insomnia severity, assessed at baseline and 2 weeks	Change in self-rated insomnia severity, assessed using the Insomnia Severity Index (ISI)	Self-rated insomnia severity, assessed at baseline, 1 week and 6 weeks
To explore whether Chloral Hydrate will affect Insomnia severity	Change in self-rated insomnia severity, assessed using the Insomnia Severity Index (ISI)	Self-rated insomnia severity, assessed at baseline, 1 week and 6 weeks
To explore whether Chloral Hydrate will affect Quality of sleep and sleep disturbances	Change in Pittsburgh Sleep Quality Index (PSQI) scores	PSQI responses assessed at baseline, 2 weeks and 6 weeks
To investigate the safety of Chloral Hydrate	Evaluation of overall safety of Chloral Hydrate by the monitoring of AEs and SAEs	AEs and SAEs for the 6 week trial duration
To investigate intervention adherence	Daily intervention adherence for the duration of the intervention (2 weeks)	Daily intervention adherence survey questions on days 1-14
To assess tolerance of Chloral Hydrate	Number of participants withdrawn from the IMP due to an AR, during the 2 week treatment period	Total number of participants withdrawn from the IMP due to an AR
To explore whether Chloral Hydrate will affect Daytime sleepiness	Change in Epworth Sleepiness Scale scores which is based on a 0-3 scale with 0 being No chance of dozing, and 3 High chance of dozing.	Epworth Sleepiness Scale scores, assessed at baseline, 1 week, 2 weeks and 6 weeks
To explore whether Chloral Hydrate will affect Health-related quality of life	Change in health-related quality of life, measured using the ShortForm 36 (SF-36) and EQ-5D-5L questionnaires. The SF-36 is based on a 1-5 with 1 being excellent and 5 poor. EQ-5D-5L is scored on a 0-100 scale with 0being the worst health possible, and 100 the best health you can imagine.	SF-36 and EQ-5D-5L responses, assessed at baseline, 1 week, 2 weeks and 6 weeks
To explore whether Chloral Hydrate will affect anxiety and Depression	Change in Hospital Anxiety and Depression Scale (HADS) scores. The scale is based on a 0-21 scale with 0-7 = Normal, 8-10 = Borderline abnormal (borderline case), 11-21 = Abnormal (case)	HADS scores, assessed at baseline, 1 week, 2 weeks and 6 weeks
To determine any reductions in the use of non-pharmacological sleep therapies	Change in use of non-pharmacological sleep therapies	Non-pharmacological sleep therapies assessed at baseline, 1 week, 2 weeks and 6 weeks
To determine any reductions in 1. Concomitant prescribed medication 2. Over the counter medication used to facilitate sleep	Change in; Concomitant medication; Over the counter medication used to facilitate sleep	1. Concomitant medication assessed at baseline, 1 week, 2 weeks and 6 weeks 2. Over the counter medication used to facilitate sleep assessed at baseline, 1 week, 2 weeks and 6 week
Medical doctor assessment of effectiveness of Chloral Hydrate	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. Rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.	CGI-S assessed at baseline, and CGI-I assessed at 2 weeks and 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess days off work	Change in percentage of days off work	Percentage of days off work one month and 12 months prior to baseline, and assessed at 2 weeks (for the 2 week treatment period) and 6 weeks (for the 4 week observation period)

Collaborators and Investigators

• Sponsor: Pharmanovia

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): April 24, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Chloral Hydrate
• Other Study ID Numbers: 1007757

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No