Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

Phase 1

Completed

• Conditions: Sleep; Insomnia
• Interventions: Drug: Dexmedetomidine; Other: Saline Placebo

• Registration Number: NCT02818569
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2016-06-13
• Study First Submitted QC: 2016-06-27
• Study First Posted: 2016-06-29
• Study Start: 2016-10
• Primary Completion: 2018-06
• Study Completion: 2018-06
• Results First Submitted: 2019-08-15
• Status Verified: 2019-10
• Results First Submitted QC: 2019-10-01
• Last Update Submitted: 2019-10-01
• Results First Posted: 2019-10-02
• Last Update Posted: 2019-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Age between 18-50
• Native English speaking
• ASA physical status classification P1 and P2 (stable chronic condition)
• Normal body habitus.

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Oral Dexmedetomidine, Then Placebo	Saline Placebo	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.
Placebo, Then Oral Dexmedetomidine	Saline Placebo	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 .
Placebo, Then Oral Dexmedetomidine	Dexmedetomidine	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 .
Oral Dexmedetomidine, Then Placebo	Dexmedetomidine	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.

Primary Outcome Measures

Name	Time	Method
Hemodynamic Stability (Phase I)	Active study night, visit 3 or 4	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.
Polysomnography Sleep Quality (Phase II).	Active study night, visit 3 or 4	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States