Clinical trial NCT06405282: Weightlessness Associated Cephalad Fluid Shifts; The Potential to Evaluate Venous and Lymphatic Dysfunction
Official title: The Use of Non-Invasive Imaging Devices (NIID) to Detect Temperature Differentiation and Lymphatic/Venous Flow to the Head and Neck During Head Down Tilt Position Before and After Manual Lymphatic Drainage: The NIID Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fluid Retention Tissue
Perfusion; Complications
Keywords: dermal flow
venous flow
fluid shift
manual lymphatic drainage
blood circulation
space simulation
diagnostic imaging
tissue temperature gradient
Lead sponsor: Nova Southeastern University
Sponsor class: OTHER
First posted: 2024-05-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy students between the ages of 18 and 45.

Brief summary: In the weightlessness of space and significant alterations of terrestrial 1 g (1 gravity equivalent) head-to-foot hydrostatic pressure gradients, astronauts experience a dramatic fluid redistribution of \~ 2 liters from the legs to the head and neck within the first 24-48 hours of flight, among other cardiovascular and physiologic system adaptations. After only 4 days in the weightlessness of low earth orbit (LEO), changes can be seen in baroreceptor responsiveness, causing orthostatic hypotension upon subsequent return to Earth. Fluid shifts may also result in headaches, congestion or facial puffiness that can contribute to deteriorating sleep patterns. The ability to manage, mitigate, or offset these fluid shifts is vital to maintain nominal health for short and long duration space flight and potentially improve readaptation to terrestrial gravity or other surface gravity fields, such as the moon or Mars. Fluid shifts towards the cephalic region during microgravity have been speculated to contribute towards spaceflight associated neuro-ocular syndrome (SANS). SANS is a distinct, microgravity-induced phenomenon of neuro-ophthalmic findings observed in astronauts following long-duration spaceflight including choroidal folds, optic disc edema, posterior globe flattening, refractive shift, and cerebral fluid shifts noted to be persistent at 6-month post-flight MRI scans. Thus, noninvasive approaches to studying real-time fluid shifts in weightlessness could serve as critical areas of research to further SANS study and effective countermeasure protocol development. For continuous fluid shift monitoring and management, the goal is to establish baseline assessments utilizing real-time point- of-care noninvasive imaging devices (NIID).

Manual lymphatic drainage (MLD) therapy reduces lymphatic fluid in the affected limb, head, and neck to improve function and prevent progression of fluid build-up. MLD is a therapeutic massage that delivers light pressure through the skin to stimulate lymphatic vessel function. Randomized controlled trials have demonstrated statistically significant improvements in lymphatic function and pain following MLD.

The main objectives of this pilot, retrospective study were to use NIID to examine temperature differential alterations, superficial venous flow patterns (head, neck, upper torso), and venous flow patterns along the lymphatic ventromedial bundles of the medial calves and thighs when in the 6-degree head down tilt (HDT) validated space analogue position and to analyze the effect of MLD therapy administered in the HDT position on lymphatic flow and temperature. HDT is the best validated space analogue currently available for evaluation of fluid redistribution in a timely manner.

Detailed description: Under the influence of standard developmental physiology on the Earth's surface (1 g), 70% of body fluids reside below the level of the heart. The lymphatic system has the capacity and capability to transport fluid from distal to proximal in an upward manner, against gravity and tissue pressure gradients, via lymphangion contractility, leg muscle contraction, respiratory and chest wall function, thus augmenting a "suction effect" for pumping lymphatic fluid within the subatmospheric pressure tissue distribution zones (the Guyton principle). Lymphatic drainage of the head and neck must be assisted by gravity, since these regions are above the level of the heart. In the weightlessness of space and significant alterations of terrestrial 1 g head-to-foot hydrostatic pressure gradients, astronauts experience a dramatic fluid redistribution of \~ 2 liters from the legs to the head and neck within the first 24-48 hours of flight, among other cardiovascular and physiologic system adaptations. After only 4 days in the weightlessness of LEO, changes can be seen in baroreceptor responsiveness, causing orthostatic hypotension upon subsequent return to Earth. Fluid shifts may also result in headaches, congestion, or facial puffiness that can contribute to deteriorating sleep patterns. The ability to manage, mitigate, or offset these fluid shifts is vital to maintain nominal health for short and long duration space flight and potentially improve readaptation to terrestrial gravity or other surface gravity fields, such as the moon or Mars. Fluid shifts towards the cephalic region during microgravity have been speculated to contribute towards spaceflight associated neuro-ocular syndrome (SANS). SANS is a distinct, microgravity-induced phenomenon of neuro-ophthalmic findings observed in astronauts following long-duration spaceflight including choroidal folds, optic disc edema, posterior globe flattening, refractive shift, and cerebral fluid shifts noted to be persistent at 6-month post-flight MRI scans. Thus, noninvasive approaches to studying real-time fluid shifts in weightlessness could serve as critical areas of research to further SANS study and effective countermeasure protocol development. For continuous fluid shift monitoring and management, the goal is to establish baseline assessments utilizing real-time point-of-care NIID.

MLD therapy reduces lymphatic fluid in the affected limb, head, and neck to improve function and prevent progression of fluid build-up. MLD is a therapeutic massage that delivers light pressure through the skin to stimulate lymphatic vessel function. Randomized controlled trials have demonstrated statistically significant improvements in lymphatic function and pain following MLD.

The main objectives of this pilot, retrospective case series were to use 4 standard-of-care NIIDs to examine temperature differential alterations, superficial venous flow patterns (head, neck, upper torso), and venous flow patterns along the lymphatic ventromedial bundles of the medial calves and thighs when in the 6-degree HDT space analogue position and to analyze the effect of MLD therapy administered in the HDT position on lymphatic flow and temperature. We hypothesize that dermal venous and lymphatic flow patterns of the head, neck, upper torso, and ventromedial bundle flow patterns shifted to cephalad (dermal interstitial fluid increase) and were reversed following MLD therapy in the 6-degree HDT position. More specifically, MLD therapy could alter lymphatic contractility flow patterns and interstitial fluid, in addition to temperature differentials, in the 6-degree HDT position.

The following imaging devices were used to measure fluid redistribution and temperature in the HDT: near-infrared spectroscopy imaging device (SnapShotNIR, Kent Imaging, Calgary, Canada) to capture perfusion changes through and superficial oxygenation saturation measurements; long-wave infrared and wound imaging device (WoundVision Scout, WoundVision, Indianapolis, IN) to capture thermal images measuring physiological temperature differentiation; Lymphatic fluid scanning device (LymphScanner, Delfin Technologies, Miami, FL, USA) to measure percentage water content \[tissue dielectric constant (TDC)\] consistent with lymphatic flow patterns and interstitial fluid alterations related to positioning.

Eligibility criteria: Inclusion Criteria:

* Students at Nova Southeastern University
* Aged 18-45 years
* Body Mass Index ranging from 18.5 to 24.9
* No known lymphatic dysfunction
* Written informed consent

Exclusion Criteria:

* On blood pressure medications
* On vasodilation medications
* Uses any form of nicotine

Primary outcomes:
measure: Percent change (%) in TDC level from baseline
timeFrame: Baseline, post-30 minutes, post-60 minutes, post-90 minutes, post-120 minutes, post-150 minutes, post-180 minutes, post-195 minutes (post-MLD), and post-225 minutes (30-minutes-post-MLD)
measure: Percent change (%) in tissue oxygenation saturation level from baseline
timeFrame: Baseline, post-30 minutes, post-60 minutes, post-90 minutes, post-120 minutes, post-150 minutes, post-180 minutes, post-195 minutes (post-MLD), and post-225 minutes (30-minutes-post-MLD).
measure: Percent change (%) in tissue temperature gradient from baseline
timeFrame: Baseline,post-30 minutes, post-60 minutes, post-90 minutes, post-120 minutes, post-150 minutes, post-180 minutes, post-195 minutes (post-MLD), and post-225 minutes (30-minutes-post-MLD).
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: Nova Southeastern University
state: Florida
Study officials:
affiliation: Nova Southeastern University
name: Heather Barnhart, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michel CC. Starling: the formulation of his hypothesis of microvascular fluid exchange and its significance after 100 years. Exp Physiol. 1997 Jan;82(1):1-30. doi: 10.1113/expphysiol.1997.sp004000. No abstract available.
citation: Debiec-Bak A, Skrzek A , Prof, Wozniewski M , Prof, Malicka I. Using Thermography in the Diagnostics of Lymphedema: Pilot Study. Lymphat Res Biol. 2020 Jun;18(3):247-253. doi: 10.1089/lrb.2019.0002. Epub 2019 Nov 19.