Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

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.

Study Overview

• Status: Completed
• Conditions: Insomnia; Sleep
• Intervention / Treatment: Other: Saline Placebo; Drug: Dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Dexmedetomidine, Then 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.	Other: Saline Placebo; Saline Placebo; Other Names: Saline; Drug: Dexmedetomidine; Oral form; Other Names: Precedex
Experimental: Placebo, Then Oral 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 .	Other: Saline Placebo; Saline Placebo; Other Names: Saline; Drug: Dexmedetomidine; Oral form; Other Names: Precedex

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2016P000269

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We are undecided.