Studying Physiological and Anatomical Cerebral Effects of Carbon Dioxide and Tilt (SPACE-COT)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: ambient air; Other: 0.5% CO2

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atmosphere 1 - 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.	Other: ambient 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
Experimental: Atmosphere 2 - 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.	Other: 0.5% 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cerebral blood flow: Transcranial doppler	Transcranial Doppler derived measurements of mean cerebral blood flow velocity	24 and 48 hours from baseline measurements
Changes in intracranial volume	Cerebrotech monitor derived intracranial fluid volume changes (percentage change)	24 and 48 hours from baseline measurements
Changes in intracranial pressure	Vittamed ICP meter derived intracranial pressure (mmHg)	24 and 48 hours from baseline measurements
Changes in cognitive function	Cognition battery score (max 1000): tests multiple cognitive domains including spatial memory, psychomotor processing speed, facial emotional recognition	24 and 48 hours from baseline measurements
Changes in cerebral blood flow: cFLOW	cFLOW derived changes in cerebral blood flow index	24 and 48 hours from baseline measurements

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of combined -12 head down tilt and 0.5% carbon dioxide	Assess safety outcomes: tolerance of condition through duration of study and number of adverse events	Within 48 hours from baseline
Changes in intraocular pressure	iCare derived intraocular pressure measurements from both eyes (mmHg)	24 and 48 hours from baseline measurements
Changes in pulmonary mechanics	minute ventilation, respiratory rate and vital capacity	24 and 48 hours from baseline measurements
Changes in internal jugular vein volumes	Ultrasound derived measure of right internal jugular vein cross sectional areas	48 hours from baseline measurements
Changes in peripheral arterial vasoreactivity	Ultrasound Doppler Measurement of arterial diameter and flow (cm/sec) after transient cuff occlusion of brachial artery	48 hours from baseline measurements
Changes in cardiac hemodynamics	Assessment of cardiac output, stroke volume, heart rate, blood pressure	48 hours from baseline measurements
Changes in olfactory threshold	Sniffin' sticks threshold testing for phenyethyl alcohol	24 and 48 hours from baseline measurement
Changes in pulmonary gas exchange	changes in arterial pH and partial pressure CO2	24 and 48 hours from baseline measurements

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The University of Texas Health Science Center, Houston; University of Pennsylvania; DLR German Aerospace Center; University of Cologne; Harvard University; National Space Biomedical Research Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 27, 2015
• First Submitted That Met QC Criteria: July 7, 2015
• First Posted (Estimate): July 10, 2015

Study Record Updates

• Last Update Posted (Estimate): January 13, 2016
• Last Update Submitted That Met QC Criteria: January 12, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Cognition; Intracranial pressure; Cerebrovascular; Brain physiology; Head down tilt; Space flight
• Other Study ID Numbers: H-36485