Healthy
Conditions
Keywords
Brain physiology, Intracranial pressure, Cognition, Cerebrovascular, Head down tilt, Space flight
Brief summary
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.
Detailed description
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.
Interventions
OTHER0.5% CO2
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
OTHERambient air
The subjects will be randomized to breath ambient air during one of the -12 degree head down tilt body position periods in crossover design
Sponsors
National Space Biomedical Research Institute
DLR German Aerospace Center
The University of Texas Health Science Center, Houston
University of Pennsylvania
Harvard University
University of Cologne
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
30 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cerebral blood flow: Transcranial doppler | 24 and 48 hours from baseline measurements | Transcranial Doppler derived measurements of mean cerebral blood flow velocity |
| Changes in intracranial volume | 24 and 48 hours from baseline measurements | Cerebrotech monitor derived intracranial fluid volume changes (percentage change) |
| Changes in intracranial pressure | 24 and 48 hours from baseline measurements | Vittamed ICP meter derived intracranial pressure (mmHg) |
| Changes in cognitive function | 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 |
| Changes in cerebral blood flow: cFLOW | 24 and 48 hours from baseline measurements | cFLOW derived changes in cerebral blood flow index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in cardiac hemodynamics | 48 hours from baseline measurements | Assessment of cardiac output, stroke volume, heart rate, blood pressure |
| Tolerability of combined -12 head down tilt and 0.5% carbon dioxide | Within 48 hours from baseline | Assess safety outcomes: tolerance of condition through duration of study and number of adverse events |
| Changes in pulmonary gas exchange | 24 and 48 hours from baseline measurements | changes in arterial pH and partial pressure CO2 |
| Changes in olfactory threshold | 24 and 48 hours from baseline measurement | Sniffin' sticks threshold testing for phenyethyl alcohol |
| Changes in intraocular pressure | 24 and 48 hours from baseline measurements | iCare derived intraocular pressure measurements from both eyes (mmHg) |
| Changes in pulmonary mechanics | 24 and 48 hours from baseline measurements | minute ventilation, respiratory rate and vital capacity |
| Changes in internal jugular vein volumes | 48 hours from baseline measurements | Ultrasound derived measure of right internal jugular vein cross sectional areas |
| Changes in peripheral arterial vasoreactivity | 48 hours from baseline measurements | Ultrasound Doppler Measurement of arterial diameter and flow (cm/sec) after transient cuff occlusion of brachial artery |
Outcome results
None listed