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Completed

NCT Number: NCT02493985

Studying Physiological and Anatomical Cerebral Effects of Carbon Dioxide and Tilt

The purpose of this study is to study the effects of carbon dioxide combined with head down tilt on cerebral physiology and anatomy. This paradigm will help establish a ground-based analog for spaceflight, and also evaluate the ability of non-invasive devices to monitor brain physiology.

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Key information

Conditions

Age range

30 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

About this study

Many of the long duration astronauts develop visual changes, associated with neuroophthalmological abnormalities suggesting elevated intracranial pressure. There is currently no suitable ground based analog to simulate these changes on Earth, or a standard methodological approach to monitoring the combined effects of head down tilt and atmospheric carbon dioxide. Given that carbon dioxide and cephalad fluid shifting are known factors in spaceflight, we sought to evaluate an approach to monitoring these effects in healthy subject in a ground based analog on Earth.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Male
  • Ages between 30 to 55 years old
  • Body Mass Index (BMI) of 20-26 kg/m2
  • Weight between 65-85 kg
  • Height between 158-190 cm
  • Non-smoker, for at least six months before the start of the study
  • VO2 max of at least 30ml/kg/min

Exclusion criteria

  • History of intracranial pressure elevation
  • History of abnormal intraocular pressure
  • Ophthalmological conditions: glaucoma, retinopathy, severe cataracts, eye trauma or implants.
  • History of diseases of the optic nerve
  • Pre-existing corneal injury
  • History of these eye surgeries: implanted lens, corneal transplant, recent (less than 6 months) LASIK surgery
  • Congenital abnormalities of the anterior chamber
  • Active eye infections, recent corneal abrasions, inflammation
  • Intraocular pressure greater than 20 mm Hg
  • Viral or bacterial eye infection Severe dry eye syndrome
  • Retinal or choroidal detachment
  • More than -6,0 dpr (high myopia)
  • More than +5,0 dpr
  • Arm or shoulder injury in the past year
  • Psychiatric conditions including major depression, bipolar disorder or severe anxiety
  • History of cerebrovascular disease including brain aneurysms, stroke, transient ischemic attack, brain hemorrhage, arteriovenous malformations History of brain tumor, congenital cysts, hydrocephalus, brain injury (requiring hospitalization)
  • Meningitis/encephalitis
  • Epilepsy
  • History of severe hypertension (> 160/90 mmHg),
  • Diabetes mellitus
  • Coronary artery disease
  • Congestive heart failure
  • Ventricular or atrial arrhythmias
  • Autonomic disorders (syncope, autoimmune neuropathy)
  • Hepatic disease
  • Renal disease
  • Chronic infections including HIV, Hepatitis B or C, Lyme disease
  • History of hematological disease including hemophilia, leukemia, thrombocytosis, thrombocytopenia, myelodysplastic syndrome, autoimmune disease (lupus, rheumatoid arthritis, Sjogren's syndrome)
  • History of malignancy except for basal cell carcinoma
  • Chronic back pain (inability to lay in bed for long periods of time)
  • Conditions that would preclude MRI including severe claustrophobia, pace maker or other metallic implants or devices
  • Sleep disturbances including: obstructive sleep apnea, narcolepsy, insomnia - Medications that exert cardiovascular, cerebrovascular or psychiatric function (i.e. beta blockers, calcium channel blockers, diuretics, diamox, sedatives) Drug, medication or alcohol abuse (regular consumption of more than 20-30 g alcohol/day)*
  • Smoking
  • VO2 max less than 30 ml/kg/min or greater than 60 ml/kg/min
  • Vegetarian, vegan
  • Migraine
  • Previous psychiatric illness
  • Hiatus hernia
  • Gastro-esophageal reflux
  • Diabetes mellitus
  • Rheumatic illness
  • Muscle or joint disorder
  • Pronounced orthostatic intolerance (< 10 min standing)
  • Hyperlipidaemia
  • Thyroid gland disorder: deviations from normal values for TSH in plasma
  • Hyper-homocysteinaemia
  • Hyperuricaemia or hypouricaemia: deviations from normal values for uric acid in plasma.
  • Hypercalcaemia or hypocalcaemia: deviations from normal values for calcium in plasma.
  • Iron deficiency
  • Vitamin D deficiency
  • Baseline blood gas values deviating from the normal reference values
  • Elevated risk of venous thromboembolism including deep venous thrombosis, pulmonary embolism
  • Chronic back complaints
  • Participation in another clinical study within the last 3 months before start of this study
  • Criminal record
  • Stomach sleepers
  • Any other medical condition that the investigators consider a contraindication to the study procedures that would make it unsafe or confound the measurements.

Treatment and study plan

0.5% CO2

Other

The subjects will be randomized to breath 0.5% carbon dioxide during one of the -12 degree head down tilt body position periods in crossover design

ambient air

Other

The subjects will be randomized to breath ambient air during one of the -12 degree head down tilt body position periods in crossover design

Primary outcomes

  1. Changes in cerebral blood flow: Transcranial doppler

    Time frame: 24 and 48 hours from baseline measurements

    Transcranial Doppler derived measurements of mean cerebral blood flow velocity

  2. Changes in intracranial volume

    Time frame: 24 and 48 hours from baseline measurements

    Cerebrotech monitor derived intracranial fluid volume changes (percentage change)

  3. Changes in intracranial pressure

    Time frame: 24 and 48 hours from baseline measurements

    Vittamed ICP meter derived intracranial pressure (mmHg)

  4. Changes in cognitive function

    Time frame: 24 and 48 hours from baseline measurements

    Cognition battery score (max 1000): tests multiple cognitive domains including spatial memory, psychomotor processing speed, facial emotional recognition

  5. Changes in cerebral blood flow: cFLOW

    Time frame: 24 and 48 hours from baseline measurements

    cFLOW derived changes in cerebral blood flow index

Secondary outcomes

  1. Tolerability of combined -12 head down tilt and 0.5% carbon dioxide

    Time frame: Within 48 hours from baseline

    Assess safety outcomes: tolerance of condition through duration of study and number of adverse events

  2. Changes in intraocular pressure

    Time frame: 24 and 48 hours from baseline measurements

    iCare derived intraocular pressure measurements from both eyes (mmHg)

  3. Changes in pulmonary mechanics

    Time frame: 24 and 48 hours from baseline measurements

    minute ventilation, respiratory rate and vital capacity

  4. Changes in internal jugular vein volumes

    Time frame: 48 hours from baseline measurements

    Ultrasound derived measure of right internal jugular vein cross sectional areas

  5. Changes in peripheral arterial vasoreactivity

    Time frame: 48 hours from baseline measurements

    Ultrasound Doppler Measurement of arterial diameter and flow (cm/sec) after transient cuff occlusion of brachial artery

  6. Changes in cardiac hemodynamics

    Time frame: 48 hours from baseline measurements

    Assessment of cardiac output, stroke volume, heart rate, blood pressure

  7. Changes in olfactory threshold

    Time frame: 24 and 48 hours from baseline measurement

    Sniffin' sticks threshold testing for phenyethyl alcohol

  8. Changes in pulmonary gas exchange

    Time frame: 24 and 48 hours from baseline measurements

    changes in arterial pH and partial pressure CO2

Sponsors and collaborators

Lead sponsor

Baylor College of Medicine

Other

Collaborators

  • DLR German Aerospace Center
  • Harvard University
  • National Space Biomedical Research Institute
  • The University of Texas Health Science Center, Houston
  • University of Cologne
  • University of Pennsylvania

Registry information

Acronym: SPACE-COT

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Jul 10, 2015
Registry last updated
Jan 13, 2016

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

View the official ClinicalTrials.gov record (opens in a new tab)

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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