Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02818569
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep; Insomnia	Drug: Dexmedetomidine; Other: Saline Placebo	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Patients will receive both the oral dexmedetomidine intervention and placebo comparator in a randomized order.Patients will receive both the oral dexmedetomidine intervention and placebo comparator in a randomized order.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Repurposing Dexmedetomidine as an Orally Administered Sleep Therapeutic
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

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.	Drug: Dexmedetomidine; Oral form; Other Names: Precedex ; Other: Saline Placebo; Saline Placebo; Other Names: Saline
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 .	Drug: Dexmedetomidine; Oral form; Other Names: Precedex ; Other: Saline Placebo; Saline Placebo; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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).

2. Performance on the Motor Sequence Task (Phase II) [Active study night, visit 3 or 4]

   Number of participants with improved MST score after sleeping.

3. Subjective Sleep Quality (Phase II) [Active study night, visit 3 or 4]

   Self-reported sleep latency.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 12, 2017

More Information

Publications

None provided.

• Responsible Party: Oluwaseun Johnson-Akeju, MD, MMSc, Assistant Professor in Anesthesia, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02818569
• Other Study ID Numbers: 2016P000269
• First Posted: Jun 29, 2016
• Last Update Posted: Oct 2, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Dexmedetomidine

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Oral Dexmedetomidine, Then Placebo	Placebo, Then Oral Dexmedetomidine
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	8	7
COMPLETED	8	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	All study participants who were either randomized to receive either Oral Dexmedetomidine or the placebo comparator initially.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 53.3%
Male	7 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	13 86.7%
Unknown or Not Reported	1 6.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	6 40%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 53.3%
More than one race	1 6.7%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Hemodynamic Stability (Phase I)
Description	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.
Time Frame	Active study night, visit 3 or 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Dexmedetomidine	Placebo Comparator
Arm/Group Description	Dexmedetomidine Type: Oral	Placebo Comparator Type: Saline
Measure Participants	15	15
SBP < 60 mmHG	0 0%	0 NaN
Hypertension	0 0%	0 NaN
Bradycardia	0 0%	0 NaN

2. Primary Outcome

Title	Polysomnography Sleep Quality (Phase II).
Description	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.
Time Frame	Active study night, visit 3 or 4

Outcome Measure Data

Analysis Population Description

All 15 Participants completed both arms of the study. After being randomized and completing a single arm, they proceeded to complete the second arm thereafter.

Arm/Group Title	Oral Dexmedetomidine	Placebo Comparator
Arm/Group Description	Oral Dexmedetomidine	Saline Saline Placebo: Saline Placebo
Measure Participants	15	15
Number [participants]	15 100%	15 NaN

3. Secondary Outcome

Title	Performance on the Psychomotor Vigilance Task (Phase II)
Description	The number of responses that were longer than 400 milliseconds (lapse 400).
Time Frame	Active study night, visit 3 or 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	Oral Dexmedetomidine Dexmedetomidine: Oral form	Saline Saline Placebo: Saline Placebo
Measure Participants	15	15
Training (Before Sleep)	5.8 (5)	6.5 (7)
Testing (After Sleep)	14.5 (15.5)	12.3 (13.2)

4. Secondary Outcome

Title	Performance on the Motor Sequence Task (Phase II)
Description	Number of participants with improved MST score after sleeping.
Time Frame	Active study night, visit 3 or 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	Oral Dexmedetomidine Dexmedetomidine: Oral form	Saline Saline Placebo: Saline Placebo
Measure Participants	15	15
Count of Participants [Participants]	12 80%	13 NaN

5. Secondary Outcome

Title	Subjective Sleep Quality (Phase II)
Description	Self-reported sleep latency.
Time Frame	Active study night, visit 3 or 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	Oral Dexmedetomidine Dexmedetomidine: Oral form	Saline Saline Placebo: Saline Placebo
Measure Participants	15	15
Mean (Standard Deviation) [minutes]	33 (24.4)	36.3 (27.3)

Adverse Events

Time Frame	Length of study conduction through visits 1-4
Arm/Group Title	Experimental		Placebo Comparator
Arm/Group Description	Oral Dexmedetomidine Dexmedetomidine: Oral form		Saline Saline Placebo: Saline Placebo
All Cause Mortality
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.