Clinical trial NCT02493985: Studying Physiological and Anatomical Cerebral Effects of Carbon Dioxide and Tilt
Official title: Studying Physiological and Anatomical Cerebral Effects of Carbon Dioxide and Tilt
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Brain physiology
Intracranial pressure
Cognition
Cerebrovascular
Head down tilt
Space flight
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: National Space Biomedical Research Institute
name: DLR German Aerospace Center
name: The University of Texas Health Science Center, Houston
name: University of Pennsylvania
name: Harvard University
name: University of Cologne
First posted: 2015-07-10
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in cerebral blood flow: Transcranial doppler
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in intracranial volume
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in intracranial pressure
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in cognitive function
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in cerebral blood flow: cFLOW
timeFrame: 24 and 48 hours from baseline measurements
Secondary outcomes:
measure: Tolerability of combined -12 head down tilt and 0.5% carbon dioxide
timeFrame: Within 48 hours from baseline
measure: Changes in intraocular pressure
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in pulmonary mechanics
timeFrame: 24 and 48 hours from baseline measurements
measure: Changes in internal jugular vein volumes
timeFrame: 48 hours from baseline measurements
measure: Changes in peripheral arterial vasoreactivity
timeFrame: 48 hours from baseline measurements
measure: Changes in cardiac hemodynamics
timeFrame: 48 hours from baseline measurements
measure: Changes in olfactory threshold
timeFrame: 24 and 48 hours from baseline measurement
measure: Changes in pulmonary gas exchange
timeFrame: 24 and 48 hours from baseline measurements
Other outcomes:
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