Studying Physiological and Anatomical Cerebral Effects of Carbon Dioxide and Tilt

Phase 1

Completed

• Conditions: Healthy
• Interventions: Other: ambient air; Other: 0.5% CO2

• Registration Number: NCT02493985
• Lead Sponsor: Baylor College of Medicine

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-27
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Study First Submitted QC: 2015-07-07
• Study First Posted: 2015-07-10
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-12
• Last Update Posted: 2016-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Atmosphere 1 - Ambient air	ambient air	First, the subjects will have 1 baseline day in the upright body position. This will be followed by 28 hours of head down tilt body position and ambient air at sea level, followed by 2 hour exposure of 3% carbon dioxide inhalation.
Atmosphere 2 - 0.5% CO2	0.5% CO2	First, the subjects will have 1 baseline day in the upright body position. This will be followed by 28 hours of head down tilt body position and air with 0.5% carbon dioxide, followed by 2 hour exposure of 3% carbon dioxide inhalation.

Primary Outcome Measures

Name	Time	Method
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 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 intracranial pressure	24 and 48 hours from baseline measurements	Vittamed ICP meter derived intracranial pressure (mmHg)
Changes in cerebral blood flow: cFLOW	24 and 48 hours from baseline measurements	cFLOW derived changes in cerebral blood flow index

Secondary Outcome Measures

Name	Time	Method
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
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 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 pulmonary gas exchange	24 and 48 hours from baseline measurements	changes in arterial pH and partial pressure CO2
Changes in internal jugular vein volumes	48 hours from baseline measurements	Ultrasound derived measure of right internal jugular vein cross sectional areas
Changes in cardiac hemodynamics	48 hours from baseline measurements	Assessment of cardiac output, stroke volume, heart rate, blood pressure
Changes in olfactory threshold	24 and 48 hours from baseline measurement	Sniffin' sticks threshold testing for phenyethyl alcohol