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Enrolling by Invitation

NCT Number: NCT04856410

Effects of Long-Duration Spaceflight on General and Spatial Cognition and Its Neural Basis

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.

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Key information

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Charité - Universitätsmedizin Berlin, Berlin, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Astronauts (according to NASA requirements)
  • 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):

  • 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).
  • 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.

Treatment and study plan

Spaceflight

Other

Exposure to the spaceflight environment on the International Space Station for 2, 6, or 12 months.

Controls

Other

No intervention

Primary outcomes

  1. Cognitive performance

    Time frame: 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)

    Cognitive efficiency across domains as determined with the Cognition test battery

  2. Local task activation Cognition

    Time frame: 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)

    fMRI local task activation while performing the MRI version of Cognition in the scanner

  3. Spatial cognition performance

    Time frame: 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)

    Accuracy and reaction times for each cognitive task as determined with the Spatial Cognition test batteries

  4. Structural brain changes

    Time frame: 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)

    Structural brain changes assessed with MRI

  5. Local task activation Spatial Cognition

    Time frame: 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)

    fMRI local task activation while performing visuospatial tasks in the scanner

  6. Brain-Derived Neurotropic Factor (BDNF)

    Time frame: 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)

    Changes in Brain-Derived Neurotropic Factor (BDNF)

Secondary outcomes

  1. Insulin-like Growth Factor 1 (IGF-1)

    Time frame: 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)

    Changes in Insulin-like Growth Factor 1 (IGF-1)

  2. Vascular Endothelial Growth Factor (VEGF)

    Time frame: 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)

    Changes in Vascular Endothelial Growth Factor (VEGF)

  3. Oxytocin

    Time frame: 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)

    Changes in Oxytocin

  4. Interleukin (IL)-1

    Time frame: 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)

    Changes in Interleukin (IL)-1

  5. Interleukin (IL)-1ra

    Time frame: 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)

    Changes in Interleukin (IL)-1ra

  6. Interleukin (IL)-10

    Time frame: 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)

    Changes in Interleukin (IL)-10

  7. Tumor Necrosis Factor a (TNFa)

    Time frame: 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)

    Changes in Tumor Necrosis Factor a (TNFa)

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • Charite University, Berlin, Germany
  • DLR German Aerospace Center
  • National Aeronautics and Space Administration (NASA)

Registry information

Official study title

Temporal Nature of Cognitive and Visuospatial Brain Domain Changes During Long-Duration Low-Earth Orbit Missions (Spatial Cognition)

Important dates

Study start
2021
Primary completion
2027
Study completion
2028
First posted
Apr 23, 2021
Registry last updated
Oct 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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