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Optimize Astronaut Sleep Medication Efficacy and Individual Effects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03526575
Recruitment Status : Completed
First Posted : May 16, 2018
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
National Aeronautics and Space Administration (NASA)

Tracking Information
First Submitted Date  ICMJE March 26, 2018
First Posted Date  ICMJE May 16, 2018
Last Update Posted Date May 16, 2018
Actual Study Start Date  ICMJE January 10, 2011
Actual Primary Completion Date July 15, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
Number of lapses of attention [ Time Frame: 3 weeks ]
The number of lapses of attention on 3 minute Psychomotor Vigilance Test
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Digit Symbol Substitution Test [ Time Frame: 3 weeks ]
    The number of correct responses
  • Descending Subtraction Test [ Time Frame: 3 weeks ]
    The number of correct responses
  • Free Recall [ Time Frame: 3 weeks ]
    The number of correctly recalled words
  • Response time to shut off alarm time [ Time Frame: 3 weeks ]
    The time subjects require to shut off the awakening simulated International Space Station (ISS) alarm
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimize Astronaut Sleep Medication Efficacy and Individual Effects
Official Title  ICMJE Operational Ground Testing Protocol to Optimize Astronaut Sleep Medication Efficacy and Individual Effects
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
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. 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. 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, 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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Sleep
  • Cognition
  • Pharmacologic Actions
Intervention  ICMJE Drug: Zolpidem
Other Name: Zaleplon
Study Arms  ICMJE
  • Placebo Comparator: 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.
    Intervention: Drug: Zolpidem
  • Placebo Comparator: 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.
    Intervention: Drug: Zolpidem
Publications * 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). pii: zsy258. doi: 10.1093/sleep/zsy258.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2018)
34
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 15, 2015
Actual Primary Completion Date July 15, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03526575
Other Study ID Numbers  ICMJE 0925-0586
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Aeronautics and Space Administration (NASA)
Study Sponsor  ICMJE National Aeronautics and Space Administration (NASA)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Smith Johnston, MD JSC NASA
Principal Investigator: David Dinges, PhD University of Pennsylvania
PRS Account National Aeronautics and Space Administration (NASA)
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP