A New Clinical Trial Underway
Sleep and Alzheimer's Disease Prevention
What is the study about?
Alzheimer's disease (AD) begins many years before the onset of memory problems (approximately 20 years earlier, around the age of 50), when amyloid and tau proteins accumulate abnormally in the brain. Finding ways to slow or prevent this process could significantly reduce the impact of AD.
Dual orexin receptor antagonists (DORAs) are a type of drug initially designed to treat insomnia. Recent research suggests that they may be capable of more than just improving sleep: they may help the brain clear out amyloid and tau before they cause the memory problems associated with AD.
One DORA in particular, daridorexant, is available in Canada and has a favourable safety and tolerance profile. We are currently testing whether daridorexant can delay or prevent the accumulation of amyloid and tau in a clinical trial. The clinical trial is for people aged 50 and over who have not been diagnosed with AD or other memory problems (unless very mild). People do not need to have a sleep disorder to participate in the study.
What does it entail?
We want to recruit 240 participants, randomly assigned to receive either 50 mg of daridorexant or a placebo every night for 12 months. We will examine changes in blood markers related to amyloid and tau proteins, memory, sleep quality, and treatment safety.
Who can participate?
Inclusion criteria
- Aged 50-90
- Sans démence (MoCA>21 ou CDR<1 dans la dernière année)
- Minimum of 6 years of formal education
- Stable psychoactive medication for 1 month prior to screening with no intention to change dose during treatment period
- Capacity to provide written consent in English or French
- Having a study partner available and willing to answer questions at the screening visit, if requested
Exclusion criteria
- Clinical diagnosis of major neurocognitive disorder
- Active use of cholinesterase inhibitors or memantine
- Unstable psychiatric condition
- Diagnosis of depressive disorders: exclusion if a moderate or severe episode occurred in the last 12 months prior to inclusion AND a PHQ-9 score ˃9 at pre-screening
- Anxiety disorders or PTSD: exclusion if a score on the GAI ˃ 8 at pre-screening
- Eating disorders: exclusion if they have an ongoing condition or if remission is ˂ 5 years
- Clinically significant active suicidal ideations
- Exclusion if C-SSRS score is 3/5 or higher. Scores of 1/5 or 2/5: to be evaluated by psychiatrist prior the enrolment in the study to confirm low risk
- Unstable medical condition in the opinion of the investigator
- Uncontrolled hypertension or cardiovascular conditions (Guideline: clinical manifestation and/or persistent elevated BP > 160/90 (at least 2 values))
- Uncontrolled diabetes (guideline: HbA1c ˃7%)
- Uncontrolled kidney disease (guideline: GFR ˂ 50% lower normal limit)
- Uncontrolled pulmonary disease (example: chronic obstructive pulmonary disease)
- Neurological conditions (examples: epilepsy, CVA, brain tumor, MS, ALS)
- Recent cardiac event (example: myocardial infarct - less than 12 months)
- Recent surgery/accident (less than 3 month)
- Cancer (current or in remission for less than 2 years)
- Known or suspected history of drug or alcohol dependence or abuse within one year of the screening visit
- Insuffisance hépatique sévère ou modérée (élévation des enzymes hépatiques : AST et/ou ALT : > 3 à 5 fois la limite supérieure de la normale et/ou bilirubine : > 1.5 à 3 fois la limite supérieure de la normale)
- Currently taking a DORA
- Allergy or significant adverse reaction to DORA
- Prise de benzodiazépines ou médicaments Z > 2 fois par semaine au cours du dernier mois
- Examples restricted z-drugs: Zopiclone, Eszopiclone, Zolpidem. Examples restricted benzodiazepines: Lorazepam, Clonazepam, Alprazolam, Diazepam, Temazepam.
- Use of major and moderate CYP3A4 inducers and inhibitors
- Use of strong central nervous system depressants, opioids, strong analgesics, antipsychotics, sedative antidepressants (case by case review with the pharmacy department). List of a few examples of medications in each of the excluded classes:
- All barbiturates such as Phenobarbital, Pentobarbital, Secobarbital, Amobarbital
- All opioids such as Morphine, Oxycodone, Hydrocodone, Codeine, Fentanyl, Methadone, Heroin
- Non-opioid strong analgesics such as ketamine
- Antipsychotics such as Haloperidol, Chlorpromazine, Olanzapine, Risperidone, Quetiapine (˃25mg – lower doses are allowed)
- Sedative antidepressants: Tricyclics such as Amitriptyline, Clozapine, Doxepin, Trimipramine, Mirtazapine (an atypical antidepressant with strong sedative properties) at higher doses (30 mg – 45 mg), low doses (7.5 mg-15 mg) are allowed. High dose of trazodone will be excluded (higher than 50 mg).
- Other exclusions: gabapentin, pregabalin, nabilone. High doses of melatonin will be excluded (higher than 6 mg).
- Women who are breast feeding or pregnant
- Clinically significant non-treated, rapid eye movement (REM) sleep behavior disorder, restless leg syndrome or parasomnia
- Diagnosis of narcolepsy
- Severe obstructive sleep apnea (OSA)
- Given that obstructive sleep apnea is often undiagnosed, individuals scoring 6 or more on the STOP-Bang questionnaire (administered during screening process) will need to be evaluated by a physician to exclude the possibility of non-treated severe sleep apnea. Severe Sleep Apnea is defined by apnea-hypopnea index (AHI) greater than 30, meaning the person experiences more than 30 episodes of breathing pauses (apneas and hypopneas) per hour of sleep. These episodes must last for at least 10 seconds each.
Read and download the consent form:
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