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Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial

Primary Purpose

Insomnia, Dementia, Frontotemporal Dementia

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Lemborexant 5 MG
Sponsored by
Nova Scotia Health Authority
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insomnia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Identified by clinician investigator to have early-onset dementia and a significant component of insomnia. Exclusion Criteria: Known sleep disorders that are contraindications for orexin antagonist therapy.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    lemborexant

    Arm Description

    The study will be an N of 1 trial over 8 weeks were treatment with lemborexant being alternated with a placebo in an "ABBABAAB" format.

    Outcomes

    Primary Outcome Measures

    Total sleep time
    Total number of hours of sleep
    Sleep onset latency (SOL)
    How long it takes to fall asleep the first time the patient goes to sleep in minutes
    Wake time after sleep onset
    How long the patient is awake overnight
    Number of night awakenings
    How many times the patient wakes overnight
    Quality of sleep
    Based on sleep quality questionnaire

    Secondary Outcome Measures

    Presence & severity of ADRs
    Monitor events that may be related to medication use
    Drop-out due to ADR
    Monitor events that may be related to medication use

    Full Information

    First Posted
    October 6, 2023
    Last Updated
    October 16, 2023
    Sponsor
    Nova Scotia Health Authority
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06093126
    Brief Title
    Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
    Official Title
    Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    December 31, 2023 (Anticipated)
    Study Completion Date
    January 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Nova Scotia Health Authority

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Insomnia is a highly common, chronic disorder that is distressful for the patient but also for caregivers and can give rise to a heavy burden on the healthcare team. Sleeping aids like benzodiazepines and other sedatives (e.g., zolpidem, zopiclone) have been widely used to help treat insomnia. However, sleeping aids are also known to cause adverse drug reactions such as drowsiness and dizziness, that increases the risk of falls, driving impairment, visual impairment, cognitive impairment, and upon discontinuation may cause paradoxical rebound insomnia, delirium, and nightmares all of which exacerbate the initial insomnia. All of the negative aspects of sleeping aid use are exaggerated for older, frail adults. Some patients experience an early (young-age) onset dementia with a substantial component of insomnia. Due to the many risks associated with traditional sleeping aids they are often inappropriate in adults living with cognitive impairment and/or frailty. Lemborexant comes from a new class of medications for insomnia. Lemborexant is a dual orexin receptor antagonist that blocks the binding of wake-promoting neuropeptides orexin A and orexin B to their receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), which is thought to suppress wake drive. Unlike other traditional sleeping aids, lemborexant has not shown to be significantly associated with driving impairment, rebound insomnia, or dependence/withdrawal symptoms. Also, in clinical trials it only rarely causes the types of adverse events associated with benzodiazepines and other traditional sedatives and is less often associated with discontinuations due to adverse events. While lemborexant is available on the Canadian market it is unclear how this medication will be tolerated by patients living with an early onset dementia. Understanding the effectiveness and tolerability of lemborexant will be helpful in an N of 1 trial to understand the details of effect and effectiveness in individual patients.
    Detailed Description
    Background & Rationale Insomnia is a highly common, chronic disorder that is distressful for the patient but also for caregivers and can give rise to a heavy burden on the healthcare team. Sleeping aids like benzodiazepines and other sedatives (e.g., zolpidem, zopiclone) have been widely used to help treat insomnia. However, sleeping aids are also known to cause adverse drug reactions such as drowsiness and dizziness, that increases the risk of falls, driving impairment, visual impairment, cognitive impairment, and upon discontinuation may cause paradoxical rebound insomnia, delirium, and nightmares all of which exacerbate the initial insomnia. All of the negative aspects of sleeping aid use are exaggerated for older, frail adults. Some patients experience an early (young-age) onset dementia with a substantial component of insomnia. Due to the many risks associated with traditional sleeping aids they are often inappropriate in adults living with cognitive impairment and/or frailty. Lemborexant comes from a new class of medications for insomnia. Lemborexant is a dual orexin receptor antagonist that blocks the binding of wake-promoting neuropeptides orexin A and orexin B to their receptors orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), which is thought to suppress wake drive. Unlike other traditional sleeping aids, lemborexant has not shown to be significantly associated with driving impairment, rebound insomnia, or dependence/withdrawal symptoms. Also, in clinical trials it only rarely causes the types of adverse events associated with benzodiazepines and other traditional sedatives and is less often associated with discontinuations due to adverse events. While lemborexant is available on the Canadian market it is unclear how this medication will be tolerated by patients living with an early onset dementia. Understanding the effectiveness, tolerability, and safety of lemborexant will be helpful in an N of 1 trial to understand the details of effect and effectiveness in individual patients living with dementia and insomnia. Hypothesis The investigators hypothesize that lemborexant will be effective and safe in the treatment of insomnia in adults living with both early-onset dementia and concomitant sleep difficulty. Objective The objective of this study is to evaluate lemborexant for efficacy and safety as a sedative medication for insomnia in adults living with both early-onset dementia and insomnia. Methods This is an investigator led N of 1 trial for adults with early onset dementia and insomnia. While this trial is designed for a particular patient case the investigators anticipate that there may be opportunities in the future for this N of 1 trial to be redeployed additional times to other adults living with early onset dementia. Study Procedures: Patients identified to have early onset dementia and insomnia by a co-principal investigator during routine patient care will be considered for the N of 1 trial. The other co-investigator will then meet the potential patient, review of the project details and study objectives. There will be a discussion of risks and benefits and the consent form will be reviewed. There will be an invitation for the patient to provide informed consent. Given that the study will include people living with dementia and cognitive impairment investigators will ensure that a caregiver or substitute decision maker will participate in these discussions as well. Once the patient provides informed consent with support from a substitute decision maker if necessary, the patient will be considered enrolled in the study and will be provided with (1) Study medication and (2) Study reporting tool. (1) Study medication will be provided for an 8 week period. Medications will be dispensed in an ABiBABAAB sequence where each letter represents 7 days of treatment, A represents placebo, Bi represents lemborexant 5mg and B represents lemborexant 10 mg. This doubly counterbalanced design to defends against both linear secular trends and nonlinear trends. Medication will be provided in 7 day packs (plastic or cardboard dosette) marked to correspond to the assigned treatment week and assigned as follows. Week 1 = placebo Week 2 = lemborexant 5mg Week 3 = lemborexant 10 mg Week 4 = placebo Week 5 = lemborexant 10 mg Week 6 = placebo Week 7 = placebo Week 8 = lemborexant 10 mg Medications will be placed inside an opaque capsule to minimize the difference in appearance for the active and inactive treatments. Dispensing details of the 3 treatments will be provided with each of the 8 week long medication supplies. Please note that there will be no washout time between treatment periods (For practical purposes, washout periods may not be necessary when treatment effects (e.g., therapeutic half-lives) are short relative to the length of the treatment periods. Since treatment half-lives are often not well characterized and vary among individuals, the safest course may be to choose treatment lengths long enough to accommodate patients with longer than average treatment half-lives and to take frequent (e.g., daily) outcome measurements. (2) The patient will also be provided with a Study reporting tool (Appendix 1) where they can record details of drug response and any other noticed events/effects. 4. The participant/caregiver will receive weekly follow up phone calls by the researcher to report the efficacy and harms that the participant experienced in the last 7 days for the 8-week duration and ensure that the treatment is being tolerated. These details will be recorded for consideration and assessment when determining patient response. 5. Efficacy outcome that will be measured in the Study Reporting tool will include: i) total sleep time, ii) sleep onset latency (SOL), iii) wake time after sleep onset (WASO), iv) sleep efficiency, v) number of awakenings to be measured nightly based on patient and caregiver estimate, vi) quality of sleep (see Appendix 2), vii) quality of life of both the patient and the caregiver. Risk outcome that will be measured will include: i) presence & severity of adverse drug reactions (ADRs) (somnolence, headache, sleep paralysis, etc.), ii) patient's willingness to drop-out due to ADRs. Furthermore, provision of follow-up care will be ensured by the co-investigator. Statistical Analysis N of 1 trials are completed with a signal analysis which analyzes the differences in effect between the periods of treatment and the periods of comparator. In this study the treatment will be lemborexant and the comparator will be placebo. Investigators will assess each of the efficacy measures and risk outcomes and then compare across periods of active treatment and comparator.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Insomnia, Dementia, Frontotemporal Dementia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Single Group Assignment
    Model Description
    The study will be an N of 1 trial over 8 weeks were treatment with lemborexant given alternated with a placebo in an "ABBABAAB" format.
    Masking
    None (Open Label)
    Masking Description
    The subject will not be aware what the treatment is.
    Allocation
    N/A
    Enrollment
    1 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    lemborexant
    Arm Type
    Experimental
    Arm Description
    The study will be an N of 1 trial over 8 weeks were treatment with lemborexant being alternated with a placebo in an "ABBABAAB" format.
    Intervention Type
    Drug
    Intervention Name(s)
    Lemborexant 5 MG
    Other Intervention Name(s)
    Lemborexant 10 MG
    Intervention Description
    The participant will receive 8 weeks of treatment Week 1 = placebo Week 2 = lemborexant 5mg Week 3 = lemborexant 10 mg Week 4 = placebo Week 5 = lemborexant 10 mg Week 6 = placebo Week 7 = placebo Week 8 = lemborexant 10 mg
    Primary Outcome Measure Information:
    Title
    Total sleep time
    Description
    Total number of hours of sleep
    Time Frame
    Daily for 8 weeks
    Title
    Sleep onset latency (SOL)
    Description
    How long it takes to fall asleep the first time the patient goes to sleep in minutes
    Time Frame
    Daily for 8 weeks
    Title
    Wake time after sleep onset
    Description
    How long the patient is awake overnight
    Time Frame
    Daily for 8 weeks
    Title
    Number of night awakenings
    Description
    How many times the patient wakes overnight
    Time Frame
    Daily for 8 weeks
    Title
    Quality of sleep
    Description
    Based on sleep quality questionnaire
    Time Frame
    Weekly for 8 weeks
    Secondary Outcome Measure Information:
    Title
    Presence & severity of ADRs
    Description
    Monitor events that may be related to medication use
    Time Frame
    Daily for 8 weeks
    Title
    Drop-out due to ADR
    Description
    Monitor events that may be related to medication use
    Time Frame
    Daily for 8 weeks

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Identified by clinician investigator to have early-onset dementia and a significant component of insomnia. Exclusion Criteria: Known sleep disorders that are contraindications for orexin antagonist therapy.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Shanna C Trenaman
    Phone
    19024484994
    Email
    shanna.trenaman@dal.ca

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Not applicable. No planned sharing of results but upon reasonable request findings may be shared if other researchers wish to pursue inclusion as part of the study team and submit ethics approval for that permission.

    Learn more about this trial

    Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial

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