Optimize Astronaut Sleep Medication Efficacy and Individual Effects

NCT ID: NCT03526575

Last Updated: 2018-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-10
• Study Completion Date: 2015-07-15

Brief Summary

In the study titled Operational Ground Testing Protocol to Optimize Astronaut Sleep Medication Efficacy and Individual Effects (Phase 11), two randomized , blinded , placebo-controlled , cross-over trials will be conducted. The hypnotic medication and the placebo will be indistinguishable by subjects. Experiment 1 will involve N=14 subjects randomized to placebo , 10 mg Zolpidem (Ambien) and 10 mg Zaleplon (Sonata) in counterbalanced order and will be awakened 90 min. post-placebo administration (half at 60 min and half at 90 min). The latter will be done to maintain some degree of blinding relative to the participants knowledge of conditions and the staff working on the protocol. Zolpidem is the most commonly , and Zaleplon is the second most commonly , used sleep aid medication used in spaceflight. Females and those subjects who have had a previous adverse experience with 10 mg zolpidem will be placed into Experiment 2, which will involve N=20 subjects randomized to placebo , 5 mg zolpidem and 10 mg zaleplon. Data acquisition for both experiments will occur in the Astronaut Quarantine Facility ("AQF") at Johnson Space Center (JSC). Experimental methods and cognitive outcomes will be the same as those used in the pilot investigation titled Develop and Implement Operational Ground Testing Protocols to Individualize Astronaut Sleep Medication Efficacy and Individual Effects (Phase I). Combined , Experiment 1 and 2 will provide data on zaleplon 10 mg compared to placebo on a total of 34 subjects consisting of astronauts and other subjects considered analogous to the astronaut population (e.g., Flight Controllers, Flight Directors , Flight Surgeons, medical residents and medical students on National Aeronautics and Space Administration (NASA) rotation, and NASA/contractor employed University of Texas Medical Branch physician's) , which will provide the larger sample needed to identify those subjects who have cognitive performance deficits on abrupt awakening to the less sedating 10 mg zaleplon.

Detailed Description

The NASA /JSC Behavioral Health and Performance (BHP) Element of Space Medicine Division , Human Research Program (HRP) is supporting a ground-based directed research study to evaluate the effects of sleep medications (relative to placebo) on astronaut and other populations analogous to the astronaut population (e.g., Flight Controllers, Flight Directors, Flight Surgeons, medical residents and medical students on NASA rotation , and NASA/contractor employed University of Texas Medical Branch physician's) cognitive performance after an abrupt awakening. The second objective of the study is to develop a protocol to select a sleep medication and dose that minimally affects an individual 's cognitive performance upon awakening. Following completion of the study , it is the intent of the BHP Element to work with Space Medicine in the transition of the data and protocol as "best practices " for medical operations provided by the Clinical Services Branch in the Space Medicine Division at the NASA Johnson Space Center.

The study aims to characterize the effects of the most commonly used sleep medications and dosages on performance after an unplanned awakening , while providing the foundation for future development of individualized protocols for sleep medication use during training and on-orbit for astronauts and analogous populations (e.g., Flight Controllers , Flight Directors , Flight Surgeons , medical residents and medical students on NASA rotation , and NASA/contractor employed University of Texas Medical Branch physician's). Findings from the study will also further inform BHP 's development of an education training program related to countermeasures for sleep loss, circadian desynchronization , fatigue, and work overload for astronauts as well as ground crews who work night shifts in support of missions. Results of the study will also inform the human system health and medical standards and requirements for future exploration missions.

The study protocol was successfully pilot tested in the study titled Develop and Implement Operational Ground Testing Protocols to Individualize Astronaut Sleep Medication Efficacy and Individual Effects (Phase I) with N=7 subjects (6 NASA flight surgeons and 1 BHP Operations professional) as subjects from March through June , 2009. The pilot study results supported the scientific feasibility of conducting a randomized , blinded , placebo controlled study of sleep medication effects on alarm-based awakenings. Preliminary analysis from the pilot study indicated differences in performance upon abrupt awakening between the sleep medication and placebo conditions. Thus, the pilot data also supported the likelihood of new scientific and clinical insights from the Phase II studies with astronauts and the additional analogous populations (e.g., Flight Controllers, Flight Directors, Flight Surgeons, medical residents and medical students on NASA rotation, and NASA/contractor employed University of Texas Medical Branch physician's) .

In the study titled Operational Ground Testing Protocol to Optimize Astronaut Sleep Medication Efficacy and Individual Effects (Phase 11), two randomized , blinded , placebo-controlled , cross-over trials will be conducted. The hypnotic medication and the placebo will be indistinguishable by subjects. Experiment 1 will involve N=14 subjects randomized to placebo , 10 mg Zolpidem (Ambien) and 10 mg Zaleplon (Sonata) in counterbalanced order and will be awakened 90 min. post-placebo administration (half at 60 min and half at 90 min). The latter will be done to maintain some degree of blinding relative to the participants knowledge of conditions and the staff working on the protocol. Zolpidem is the most commonly , and Zaleplon is the second most commonly , used sleep aid medication used in spaceflight. Females and those subjects who have had a previous adverse experience with 10 mg zolpidem will be placed into Experiment 2, which will involve N=20 subjects randomized to placebo , 5 mg zolpidem and 10 mg zaleplon. Data acquisition for both experiments will occur in the Astronaut Quarantine Facility ("AQF") at JSC. Experimental methods and cognitive outcomes will be the same as those used in the pilot investigation titled Develop and Implement Operational Ground Testing Protocols to Individualize Astronaut Sleep Medication Efficacy and Individual Effects (Phase I). Combined , Experiment 1 and 2 will provide data on zaleplon 10 mg compared to placebo on a total of 34 subjects consisting of astronauts and other subjects considered analogous to the astronaut population (e.g., Flight Controllers, Flight Directors , Flight Surgeons, medical residents and medical students on NASA rotation, and NASA/contractor employed University of Texas Medical Branch physician's) , which will provide the larger sample needed to identify those subjects who have cognitive performance deficits on abrupt awakening to the less sedating 10 mg zaleplon.

This is an applied study and it is not feasible to include two or three doses of each drug in order to determine a dose-response curve based on each of the drugs pharmacodynamics. Literature has shown that zaleplon 10 mg will be less disruptive on performance at awakening than zolpidem 10 mg and that zaleplon 20 mg is likely to be comparable in effects to zolpidem 10 mg. However , zaleplon 20 mg is not a commonly used dose in space, whereas zolpidem 10 mg and 5mg, and zaleplon 10 mg are used-hence the study will focus on these drugs and doses. More importantly , the goal of this study is not to determine whether these dose-by-drug comparisons are likely to yield the same average results in astronauts as has been found in the general population (e.g., Roehrs et a., 1994; Wesensten et al., 1996; Greenblatt et al., 1998; Hindmarch et al., 2001). Instead , we began by are focusing on individual astronaut vulnerability to hypnotic sedation on awakening , and having a limited number of astronauts who can realistically participate in the operational research was not realistic or conducive in completing the study. We needed to expand our astronaut population to include international astronauts and other populations deemed analogous to the astronaut population (e.g., Flight Controllers, Flight Directors , Flight Surgeons, medical residents and medical students on NASA rotation,and NASA/contractor employed University of Texas Medical Branch physician's) . We want to evaluate as many astronauts on these drugs and doses as possible , and in a manner that permits comparisons between both drug type and dose; however , it became necessary to broaden our subject pool in order to reach the desired N. Thus Experiment 1 will evaluate 10 mg zolpidem for males and zaleplon 10 mg relative to placebo in N=14 astronauts and analogous subjects (e.g., Flight Controllers, Flight Directors, Flight Surgeons, medical residents and medical students on NASA rotation,and NASA/contractor employed University of Texas Medical Branch physician's). Experiment 2 will evaluate zolpidem 5 mg and zaleplon 10 mg relative to placebo in N = 20 additional astronauts and other analogous subjects (e.g., Flight Controllers , Flight Directors , Flight Surgeons, medical residents and medical students on NASA rotation,and NASA/contractor employed University of Texas Medical Branch physician's).

Conditions

Sleep; Cognition; Pharmacologic Actions

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

10 mg Zolpidem and 10 mg Zaleplon

Experiment 1 will involve N= 14 subjects randomized to placebo , 10 mg zolpidem for males and 10 mg zaleplon in counterbalanced order. Subjects are nested into group.

Group Type: PLACEBO_COMPARATOR

Zolpidem

Intervention Type: DRUG

5 mg Zolpidem and 10 mg Zaleplon

Experiment 2, which will involve N=20 subjects randomized to placebo, 5 mg zolpidem and 10 mg zaleplon. All females will be placed in experiment 2. Subjects are nested into group.

Group Type: PLACEBO_COMPARATOR

Zolpidem

Intervention Type: DRUG

Interventions

Zolpidem

Intervention Type: DRUG

Other Intervention Names

Zaleplon

Eligibility Criteria

Inclusion Criteria

The participant must be an active astronaut or analogous to the astronaut population (e.g., Flight Controllers, Flight Directors, Flight Surgeons, medical residents and medical students on NASA rotation, and NASA /contractor employed University of Texas Medical Branch physician's) to participate in the study. Not Applicable (NA)

Exclusion Criteria

Pregnancy

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Aeronautics and Space Administration (NASA)

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Smith Johnston, MD

Role: PRINCIPAL_INVESTIGATOR

JSC NASA

David Dinges, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

References

Dinges DF, Basner M, Ecker AJ, Baskin P, Johnston SL. Effects of zolpidem and zaleplon on cognitive performance after emergent morning awakenings at Tmax: a randomized placebo-controlled trial. Sleep. 2019 Mar 1;42(3):zsy258. doi: 10.1093/sleep/zsy258.

Reference Type: DERIVED

PMID: 30576525 (View on PubMed)

Other Identifiers

0925-0586

Identifier Type: -

Identifier Source: org_study_id