Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

Study Overview
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Brief Summary
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The broad objective of this investigation is to assess the safety and efficacy of oral therapy with dexmedetomidine for the induction and maintenance of restful sleep.

Detailed Description
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Sleep is a basic human function that occupies approximately one-third of our lives. Much of what is known about the benefits of sleep in humans has been obtained from studies of patients with insomnia, the most common sleep disorder with a reported prevalence of 10 to 15%. Unfortunately, insomnia is an independent risk factor for acute myocardial infarction, coronary heart disease, heart failure, hypertension, diabetes, and death. More so, sleep disturbances lead to neurocognitive deficits such as delirium and psychosis. However, the principal medications (i.e. benzodiazepines, zolpidem) currently used to treat insomnia are associated with side effects such as daytime sedation, delirium, anterograde memory disturbance, and complex sleep-related behaviors. We recently found that a nighttime intravenous bolus administration of dexmedetomidine was associated with normal sleep architecture comprising of rapid eye movement (REM) and non-REM (N1, N2, N3) sleep, with improved next-day psychomotor vigilance performance compared to zolpidem. Presently, dexmedetomidine is only available in an intravenous formulation. The goal of this project is to develop dexmedetomidine, an alpha-2 receptor agonist, into an oral sleep therapeutic with a neurocognitive sparing profile.

Official Title
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Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

Conditions
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Sleep, Insomnia

Intervention / Treatment
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* Drug: Dexmedetomidine
* Other: Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-50 Native English speaking ASA physical status classification P1 and P2 (stable chronic condition) Normal body habitus. Exclusion Criteria: Abnormal sleep habits Sleeping less than 5 hours each night Going to sleep before 9:00 PM or after 2:00 AM on a regular basis Waking up before 5:00 AM or after 10:00 AM on a regular basis. Takes medication that alters sleep, cognitive function, or both. -Has a history of a known neurological or psychiatric problem. Younger than 18 or older than 50 years of age. Known or suspected sleep disorder(s).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients will receive both the oral dexmedetomidine intervention and placebo comparator in a randomized order.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Dexmedetomidine, Then Placebo<br>This arm will enroll healthy control subjects, who will have an acclimation night followed by a night's sleep with oral dexmedetomidine and then a night's sleep with a placebo comparator. | Drug: Dexmedetomidine<br>* Oral form<br>* Other names: Precedex;Other: Saline Placebo<br>* Saline Placebo<br>* Other names: Saline;|
| Experimental: Placebo, Then Oral Dexmedetomidine<br>This arm will enroll healthy control subjects, who will have an acclimation night followed by a night's sleep with a placebo comparator and then a night's sleep with oral dexmedetomidine . | Drug: Dexmedetomidine<br>* Oral form<br>* Other names: Precedex;Other: Saline Placebo<br>* Saline Placebo<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamic Stability (Phase I) | Number of participants with (1) systolic blood pressure (SBP) < 60 mmHg, diastolic blood pressure (DBP) < 40 mmHg or decrease of SBP by ≥ 50 % from the baseline which is sustained over two consecutive minutes, (2) hypertension: SBP > 180 mmHg, DBP > 100 mmHg, or increase of SBP by ≥ 50 % from the baseline which is sustained over two minutes and, (3) bradycardia: heart rate (HR) < 40 bpm or decrease by ≥ 50 % from the baseline sustained over two consecutive minutes. | Active study night, visit 3 or 4 | 
| Polysomnography Sleep Quality (Phase II). | Number of participants who had EEG features of natural sleep. Relative quantities of spindles and k-complexes were used to assess approximation to natural sleep. | Active study night, visit 3 or 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance on the Psychomotor Vigilance Task (Phase II) | The number of responses that were longer than 400 milliseconds (lapse 400). | Active study night, visit 3 or 4 | 
| Performance on the Motor Sequence Task (Phase II) | Number of participants with improved MST score after sleeping. | Active study night, visit 3 or 4 | 
| Subjective Sleep Quality (Phase II) | Self-reported sleep latency. | Active study night, visit 3 or 4 |