Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02818569

Enrollment

Registered

2016-06-29

Start date

2016-10-31

Completion date

2018-06-30

Last updated

2019-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insomnia, Sleep

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.

Interventions

DRUGDexmedetomidine

Oral form

OTHERSaline Placebo

Saline Placebo

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Intervention model description

Patients will receive both the oral dexmedetomidine intervention and placebo comparator in a randomized order.

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

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).

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Pre-assignment details

All 15 participants completed both arms (dexmedetomidine and placebo) for the study. After being randomized and completing the first arm, patients completed the alternative arm thereafter.

Participants by arm

Arm	Count
All Study Participants All study participants who were either randomized to receive either Oral Dexmedetomidine or the placebo comparator initially.	15
Total	15

Baseline characteristics

Characteristic	All Study Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	8 Participants
Region of Enrollment United States	15 participants
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 15
other Total, other adverse events	0 / 15	0 / 15
serious Total, serious adverse events	0 / 15	0 / 15

Outcome results

Primary

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.