Thigh Cuffs for Fluid Shift in Healthy Subjects

Overseen By Brandon R Macias, PhD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: National Aeronautics and Space Administration (NASA)

Must not be taking: Ethinyl estradiol

Disqualifiers: Allergies to proparacaine, VTE risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests thigh cuffs to manage fluid shifts in astronauts during space missions. These Venoconstrictive Thigh Cuffs (VTC) aim to counteract fluid movement toward the head in weightlessness, potentially preventing eye issues known as SANS. Participants will experience different stages of wearing the cuffs before and during their flight. The trial suits astronauts on missions lasting two months or more, who do not have certain allergies or a high risk of blood clots. As an unphased trial, it offers astronauts a unique opportunity to contribute to innovative solutions for space health challenges.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are using ethinyl estradiol Combined Oral Contraceptive (COC) pills, you cannot participate.

What prior data suggests that these Venoconstrictive Thigh Cuffs are safe for use in healthy subjects?

Research has shown that special thigh cuffs can help control fluid movement in the body during situations like space travel or long periods of bed rest. Studies suggest these cuffs do not pose significant medical risks. For example, one study found no major side effects when participants used these thigh cuffs to manage fluid movement.

The cuffs work by gently squeezing the thighs, aiding in fluid control throughout the body. They have been tested in conditions similar to space without causing harm. Overall, evidence suggests these thigh cuffs are safe to use, with no serious side effects reported in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Venoconstrictive Thigh Cuffs (VTC) because they offer a novel approach to managing fluid shifts in the body, especially in unique environments like space. Unlike traditional methods that may rely on medications to manage fluid distribution, VTCs are a non-invasive, mechanical solution that can be worn to directly influence blood flow. This technique could potentially provide an immediate and adjustable way to counteract fluid shifts, which is particularly advantageous for astronauts experiencing prolonged periods in microgravity. The ability to study these effects in-flight offers a real-time understanding of the cuff's impact, making it a promising tool for space travel and possibly other applications on Earth.

What evidence suggests that the Venoconstrictive Thigh Cuff is effective for reversing headward fluid shift?

Studies have shown that Venoconstrictive Thigh Cuffs (VTC) can help reduce the upward movement of body fluids that occurs in weightlessness, such as in space. This fluid movement can increase pressure in the head and eyes, causing problems for astronauts. Research indicates that the thigh cuffs work by gently squeezing the legs to prevent fluids from moving upward. Initial findings suggest that VTCs can reduce the swelling of the optic nerve sheath, a significant change during space travel. In this trial, participants will use VTCs to further evaluate their effectiveness in managing these fluid shifts and protecting astronauts' health in space. ^{6 7 8 9 10}

Who Is on the Research Team?

Brandon R Macias, PhD

Principal Investigator

National Aeronautics and Space Administration (NASA)

Are You a Good Fit for This Trial?

This trial is for healthy individuals who are interested in participating in a study that involves wearing Venoconstrictive Thigh Cuffs (VTC). The cuffs are tested to see if they can counteract fluid movement towards the head in zero gravity, which could help with space-related health issues.

Inclusion Criteria

Astronauts participating in missions that are ≥2 months

Exclusion Criteria

Having known allergies to proparacaine hydrochloride ophthalmic solution precludes participation in this study

I do not have a high risk of blood clots based on tests.

I am not using birth control pills containing ethinyl estradiol.

Timeline for a Trial Participant

Preflight

Participants undergo VTC fit check and baseline data collection without and with the VTC donned

90 days before mission

2 visits (in-person)

Inflight

Participants undergo VTC fit check and data collection sessions during the mission

45 days into mission and 45 days before return

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the mission

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venoconstrictive Thigh Cuff (VTC)

Trial Overview

The effectiveness of Venoconstrictive Thigh Cuffs (VTC) is being studied. Participants will undergo two preflight sessions to check the fit and collect baseline data, then three inflight sessions including another fit check and data collection before and after wearing the VTC on specific flight days.

How Is the Trial Designed?

Group I: Flight Thigh Cuff Crew Participants Experimental Treatment 1 Intervention

Participants will participate in 2 preflight study sessions consisting of a VTC fit check and a baseline data collection without and with the VTC donned. Participants will also participate in 3 inflight study sessions: a VTC fit check on flight day 30 (FD30) and two separate data collection sessions on flight day 45 (FD45) and 45 days before landing (R-45). During the two in-flight data collection days, participants will be studied before and for up to 6 hours after donning the VTC.

Who Is Running the Clinical Trial?

National Aeronautics and Space Administration (NASA)

Lead Sponsor

Trials

32

Recruited

1,900+

Published Research Related to This Trial

Thigh cuffs worn by healthy volunteers during a 7-day head-down bed rest simulation effectively limited fluid shift and reduced headache symptoms, as well as minimizing plasma volume loss compared to not using the cuffs.

While thigh cuffs did not significantly improve overall orthostatic tolerance or the duration of standing tests, they did help mitigate increases in heart rate during orthostatic stress, suggesting a potential benefit in managing cardiovascular responses to fluid shifts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest. Pavy-Le Traon, A., Maillet, A., Vasseur Clausen, P., et al.[2019]

The occlusive cuffs (Braslet) positively impacted the health of cosmonauts during the first month of their long-term missions by improving cerebral hemodynamics and reducing venous congestion, as observed in a study involving seven cosmonauts.

While the cuffs initially did not affect leg vein capacity, they led to progressive vein expansion and changes in vein properties over time, indicating potential benefits for lower extremity circulation, though the long-term safety of continuous use remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of prophylactic device "Braslet" on hemodynamic changes during long-term missions to orbital station Mir]. Fomina, GA., Kotovskaia, AR., Temnova, EV.[2008]

Wearing venoconstrictive thigh cuffs during 7 days of head-down bed rest helped limit plasma volume loss and reduced heart rate changes, indicating some benefit in managing cardiovascular deconditioning.

Despite these benefits, thigh cuffs were not effective in preventing orthostatic intolerance, as participants still experienced similar standing times compared to the control group, suggesting that other physiological factors also play a significant role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest. Custaud, MA., Millet, C., Frutoso, J., et al.[2013]

In a study involving 12 healthy male volunteers, the use of thigh cuffs at 40 mmHg for 10 hours a day during 10 days of head-down tilt bed rest helped improve orthostatic tolerance, allowing participants to remain upright longer after the bed rest.

While thigh cuffs did not fully prevent decreases in blood flow in the middle cerebral artery, they were effective in mitigating the negative effects of fluid shifts associated with prolonged bed rest, indicating their potential utility in space flight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of thigh cuffs on haemodynamic changes of the middle cerebral artery and on orthostatic intolerance induced by 10 days head-down bed rest. Yao, YJ., Jiang, SZ., Jiang, CL., et al.[2008]

In a study involving 18 healthy men undergoing a 5-day dry immersion simulation of microgravity, thigh cuffs worn for 10 hours a day helped limit the loss of body water and plasma volume, which are typically reduced during microgravity conditions.

Despite the thigh cuffs' effectiveness in mitigating fluid loss, they did not improve orthostatic tolerance, indicating that while they may help with fluid dynamics, they do not fully counteract the cardiovascular challenges posed by microgravity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid Changes but Not Orthostatic Intolerance Induced by a 5-Day Dry Immersion. Robin, A., Auvinet, A., Degryse, B., et al.[2020]

In a study involving one subject after 5 days in space, it was found that interstitial fluid loss contributes to cardiovascular deconditioning, as evidenced by significant changes in body fluid distribution detected through electrical impedance methods.

The lower body negative pressure (LBNP) test demonstrated that higher levels of LBNP can effectively refill interstitial spaces in the legs, counteracting some effects of microgravity on cardiovascular function, particularly during orthostatic stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orthostatic stress by lower body negative pressure and its body fluid distribution kinetics under microgravity. Baisch, FJ.[2006]

In a study involving 10 healthy male subjects, venoconstrictive thigh cuffs inflated to 50 mmHg during simulated microgravity significantly increased leg volume by 3.0%, helping to counteract fluid redistribution effects typically seen in microgravity environments.

The use of these cuffs did not result in any significant changes in systemic cardiovascular parameters, suggesting they are a safe intervention that could help manage symptoms of fluid shifts, such as cephalad edema, associated with space adaptation syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venoconstrictive thigh cuffs impede fluid shifts during simulated microgravity. Lindgren, KN., Kraft, D., Ballard, RE., et al.[2006]

Wearing thigh cuffs for 10 hours daily during a 7-day head-down bed rest helped reduce the decrease in plasma volume, showing a protective effect against fluid shifts in the body.

Despite this reduction in plasma volume loss, thigh cuffs did not improve symptoms of orthostatic intolerance, indicating they are not a fully effective solution for counteracting the effects of prolonged bed rest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptations to a 7-day head-down bed rest with thigh cuffs. Millet, C., Custaud, MA., Allevard, AM., et al.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

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DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid ...

Thigh cuffs are effective in alleviating the symptoms associated with cephalad fluid shift in the early hours and days in space (Arbeille et al.

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ntrs.nasa.gov

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MITIGATING HEADWARD FLUID SHIFTS WITH VENO- ...

The study uses Veno-Constrictive Thigh Cuffs (VTC) to mitigate headward fluid shifts during spaceflight, hypothesizing it will reverse or attenuate ocular and ...

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frontiersin.org

frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.692361/full

Effects of Venoconstrictive Thigh Cuffs on Dry Immersion ...

These findings suggest that 5 days of DI induced significant ophthalmological changes. VTC were found to dampen the ONSD enlargement induced by DI.

4.

researchgate.net

researchgate.net/publication/13467852_Venoconstrictive_thigh_cuffs_impede_fluid_shifts_during_simulated_microgravity

Venoconstrictive thigh cuffs impede fluid shifts during ...

This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity.

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abstractscorecard.com

abstractscorecard.com/uploads/Tasks/upload/21810/DPPWZUCK-1647381-1-PDF.pdf

mitigating headward fluid shifts with veno-constrictive thigh cuffs

The purpose of this study is to evaluate the efficacy of using the NASA VTC to reverse the headward fluid shift during spaceflight and inform use of VTC as a ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11891356/

Mechanical countermeasures for spaceflight-associated neuro ...

Both countermeasures, venous thigh constriction and LBNP, could pose specific medical risks. In our study, we did not observe clinically ...

7.

ntrs.nasa.gov

ntrs.nasa.gov/api/citations/20110010986/downloads/20110010986.pdf

Cardiac and Vascular Responses to Thigh Cuffs and ...

Venoconstrictive thigh cuffs impede fluid shifts during simulated microgravity. Aviat Space Environ Med 1998 Nov;69(11):1052-8. (35) Tei C, Nishimura RA ...

8.

journals.physiology.org

journals.physiology.org/doi/full/10.1152/japplphysiol.00557.2011

Cardiac and vascular responses to thigh cuffs and ...

Notwithstanding the massive fluid shift, invasive central venous pressure (CVP) measurements in spaceflight have shown it to decrease to 2 mmHg with no ...

9.

withpower.com

withpower.com/trial/phase-healthy-subjects-hs-2-2023-8c7ad

Thigh Cuffs for Fluid Shift in Healthy Subjects

Research shows that venoconstrictive thigh cuffs can help limit fluid shifts in the body during conditions that simulate microgravity, like space travel or bed ...

10.

nature.com

nature.com/articles/s41526-024-00389-1

Systematic review of the effectiveness of standalone ...

Thigh cuffs (aka “bracelets”) apply about 30–40 mmHg of pressure to the thighs in order to reduce venous return to the heart from the lower ...