Clinical trial NCT04856410: Effects of Long-Duration Spaceflight on General and Spatial Cognition and Its Neural Basis
Official title: Temporal Nature of Cognitive and Visuospatial Brain Domain Changes During Long-Duration Low-Earth Orbit Missions (Spatial Cognition)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Brain Structure
Cognitive Performance
Keywords: Astronauts
Spaceflight
Cognition
Long Duration Spaceflight
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Aeronautics and Space Administration (NASA)
name: DLR German Aerospace Center
name: Charite University, Berlin, Germany
First posted: 2021-04-23
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will investigate 10 astronauts on 12-month ISS missions, 10 astronauts on 12-month ISS missions, 10 astronauts on 12-month ISS missions and 10 control subjects that are matched to 12-month mission astronauts and investigated at similar time points.
Primary purpose: BASIC_SCIENCE

Brief summary: This study investigates the effects of extended-duration spaceflight (12-month International Space Station missions) on general cognitive performance (measured with the Cognition test battery), spatial cognition, structural and functional brain changes in general, and hippocampal plasticity more specifically relative to the shorter 6-month and 2-month missions.

Detailed description: This is an international proposal consisting of two projects with synergistic aims that will be carried out in a joint effort by the National Aeronautics and Space Administration (NASA) and the German Aerospace Center (DLR) as well as the European Space Agency (ESA). The project targets NASA's particular interest in studying the 'Cognitive-perceptual-visuospatial brain domain changes due to isolation and confinement' as part of the Complement of Integrated Protocols for Human Exploration Research (CIPHER) project on the International Space Station (ISS). The collected data will demonstrate whether prolonging mission duration to one year will have detrimental effects on general cognitive performance (measured with the Cognition test battery), spatial cognition, structural and functional brain changes in general, and hippocampal plasticity more specifically relative to the shorter 6-month and 2-month ISS missions. Using state-of-the-art neuroimaging techniques, investigators will determine the biological basis for any changes in cognitive performance, with a focus on hippocampal plasticity and spatial cognition. Similar data already gathered on the ISS and in several short- and long-duration space analog environments will be used to generate a normative data base for long-duration missions. Finally, investigators will derive dose-response relationships between cognitive-visuospatial brain domain changes and mission duration that will allow predicting vulnerability to adverse cognitive or behavioral impairment and psychiatric disorders on interplanetary expeditions such as a mission to Mars. The two projects will deliver a highly unique and comprehensive set of integrated neuroimaging and neurocognitive tools for the evaluation and ultimately prevention of adverse effects on brain structure and function that lead to behavioral effects associated with exploration-type missions.

Eligibility criteria: Inclusion Criteria:

1. Astronauts (according to NASA requirements)
2. Normal, healthy volunteers (astronaut surrogates) - Astronaut surrogates will be matched for sex, age and education relative to astronauts

Exclusion Criteria:

For astronauts and normal, healthy volunteers (astronaut surrogates):

1. Subjects that do not comply with the MRI testing requirements. The following and other conditions may exclude the subject from MRI scanning or require additional examination to assess specific contraindications:

   * Tinnitus;
   * Sensori-neural hearing loss \> 30 decibels (dB);
   * Pace-maker or internal defibrillator;
   * metallic implants (e.g. orthopedic plates after bone fractures, joint replacements, surgical staples or clips, artificial heart valves, stents, cava filters);
   * Metallic splinters (e.g. after an accident or due to war injury);
   * Non-removable dental brace;
   * Intrauterine contraceptive devices (IUD) that are not MRI-compatible;
   * Cochlear implant (implanted hearing device);
   * Medication pump;
   * Acupuncture needle;
   * Other foreign bodies/objects which are non-removable;
   * Pregnancy (or its possibility);
   * Previous brain and/or heart surgery.
   * Tattoos and/or permanent make-up in the body (some inks contain metallic particles).
2. Female subjects in this study are either astronauts or will model those in the astronaut population for whom participation in space missions is not allowed during pregnancy.

Primary outcomes:
measure: Cognitive performance
timeFrame: Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 6 tests, 12 months = 12 tests)
measure: Local task activation Cognition
timeFrame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth)
measure: Spatial cognition performance
timeFrame: Change from pre-flight performance (average of tests performed 180, 120 and 60 days prior to launch) to in-flight performance (average of all tests: 1 month mission = 1 test, 2 months = 2 tests, 6 months = 4 tests, 12 months = 7 tests)
measure: Structural brain changes
timeFrame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight (investigated 5 days and 30 days after return to Earth)
measure: Local task activation Spatial Cognition
timeFrame: Change from pre-flight local task activation (investigated 60 days prior to launch) to post-flight local task activation (investigated 5 days and 30 days after return to Earth)
measure: Brain-Derived Neurotropic Factor (BDNF)
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
Secondary outcomes:
measure: Insulin-like Growth Factor 1 (IGF-1)
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Vascular Endothelial Growth Factor (VEGF)
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Oxytocin
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Interleukin (IL)-1
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Interleukin (IL)-1ra
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Interleukin (IL)-10
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
measure: Tumor Necrosis Factor a (TNFa)
timeFrame: Change from pre-flight values (average of blood drawn180 and 60 days prior to launch) to in-flight values (average of all in-flight blood draws: 1 month mission = 1 draw, 2 months = 2 draws, 6 months = 4 draws,12 months = 7 draws)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Houston
country: United States
facility: Johnson Space Center (JSC)
state: Texas
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
References:
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