Treatments for Orthostatic Intolerance

(Lunar OI Trial)

Overseen By Lucinda M Yu, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Aeronautics and Space Administration (NASA)

Must not be taking: Aspirin, NSAIDs, Antibiotics, others

Disqualifiers: Renal disease, Type II Diabetes, others

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

Compensation: Varies

Number of Visits: 3

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how males and females respond to being tilted at different angles, simulating reduced gravity like on the Moon, to understand orthostatic intolerance (difficulty standing upright due to blood pressure changes). Researchers aim to determine if a special compression garment helps manage these effects. Participants will take furosemide (Lasix), a drug that reduces blood fluid levels, mimicking conditions astronauts experience. Ideal candidates can pass a specific physical exam and do not have allergies to certain medications or conditions affecting their heart or kidneys. As an unphased trial, this study offers participants a unique opportunity to contribute to groundbreaking research that could improve astronaut health and safety.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are known to adversely interact with furosemide, such as aspirin, NSAIDs (non-steroidal anti-inflammatory drugs), antibiotics, or immunosuppressant drugs. Additionally, if you are on medications that influence the cardiovascular system, you may not be eligible to participate.

What prior data suggests that the compression garment and treatments are safe for use in this study?

Research has shown that furosemide, a common water pill, helps the body eliminate excess fluid and is often used to treat high blood pressure and swelling. While effective, it can sometimes affect heart function, potentially increasing the risk of sudden heart problems, especially with long-term use and in certain individuals. Furosemide is usually taken with a potassium supplement to replace the potassium lost due to the water pill. No known direct interactions exist between these two, but caution is always advised.

For those using a compression garment along with furosemide and a potassium supplement, there is good news. Studies have shown that compression garments can help lower heart rate and improve symptoms in people who feel dizzy or lightheaded when standing. These garments work by applying pressure to the lower body, aiding blood flow and preventing faintness.

Overall, the treatments in this trial are considered safe, especially since furosemide is already approved for other uses. Knowing these safety details can help prospective participants make an informed decision about joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for orthostatic intolerance because they combine furosemide, a diuretic, with a potassium supplement to address fluid balance in the body. Unlike standard treatments that often focus on medication to manage blood pressure or increase fluid intake, this approach specifically targets the underlying issue of blood volume. Additionally, one of the experimental treatments includes an orthostatic intolerance garment (OIG), which is designed to help maintain blood circulation. This combination of medication and garment support offers a fresh perspective on managing symptoms by addressing both fluid retention and circulation issues directly.

What evidence suggests that this trial's treatments could be effective for orthostatic intolerance?

In this trial, participants will be assigned to different treatment arms to manage orthostatic intolerance. One arm will receive furosemide, a type of water pill used to treat high blood pressure and swelling from heart failure, along with a potassium supplement to prevent low potassium levels. Research has shown that furosemide helps the body eliminate extra fluid, which can lower blood pressure, but it can affect heart function, necessitating a potassium supplement.

Another arm will receive the same combination of furosemide and potassium supplement, plus a compression garment. Studies have found that compression garments can lower heart rate and improve symptoms during tests that mimic standing up after lying down, helping to prevent dizziness or fainting linked to orthostatic intolerance. Wearing compression garments can also help prevent these symptoms after long periods of bed rest. Together, these treatments aim to better manage orthostatic intolerance. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy men and women to study how they handle changes in body position that simulate the gravity levels astronauts face during lunar missions. Participants must be able to tolerate medication that reduces blood fluid levels, similar to conditions in space.

Inclusion Criteria

I passed a specific physical fitness test.

Exclusion Criteria

I am not taking medications that negatively interact with furosemide.

Pregnant participants will be excluded (a urine pregnancy screen will be made available)

Known allergy to furosemide or sulfa drugs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Tilt Familiarization and Normovolemic Tilt Test

Participants undergo tilt familiarization and normovolemic tilt tests to simulate gravity levels experienced during lunar descent and ascent.

1 day

1 visit (in-person)

Phase I: Plasma Volume Measurement and Hypovolemic Tilt Tests

Plasma volume is measured, and participants undergo hypovolemic tilt tests at different gravity levels after furosemide infusion.

1 day

1 visit (in-person)

Phase II: OIG Fit Check and Hypovolemic Tilt Tests with Garment

Participants don custom OIG garments and repeat hypovolemic tilt tests to assess the garment's effect on orthostatic intolerance.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the completion of tilt tests.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Compression Garment
• Furosemide
• Potassium Supplement

Trial Overview The study tests if a compression garment can help with orthostatic intolerance (difficulty adjusting to standing up) by simulating Moon gravity through tilting angles. It also examines differences between males and females using potassium supplements, Furosemide (a diuretic), and the garment.

How Is the Trial Designed?

Group I: Hypovolemic plus garment Experimental Treatment 3 Interventions

Furosemide and potassium supplement plus OIG.

Group II: Hypovolemic Experimental Treatment 2 Interventions

Furosemide and potassium supplement.

Group III: Control Active Control 1 Intervention

Furosemide is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Lasix for:

• Hypertension
• Edema associated with congestive heart failure
• Liver cirrhosis
• Renal disease
• Nephrotic syndrome

Approved in United States as Lasix for:

• Edema associated with congestive heart failure
• Liver cirrhosis
• Renal disease
• Nephrotic syndrome
• Acute pulmonary edema

Approved in Canada as Lasix for:

• Edema associated with congestive heart failure
• Liver cirrhosis
• Renal disease
• Nephrotic syndrome
• Hypertension

Approved in Japan as Lasix for:

• Edema associated with congestive heart failure
• Liver cirrhosis
• Renal disease
• Nephrotic syndrome

Approved in China as Lasix for:

• Edema associated with congestive heart failure
• Liver cirrhosis
• Renal disease
• Nephrotic syndrome
• Hypertension

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

In a study involving 49 heart failure patients on furosemide, potassium supplements, spironolactone, or amiloride were administered for 5 months, leading to increased plasma potassium levels.

Despite the rise in plasma potassium, there was no significant increase in total body or red cell potassium, indicating that heart failure patients on diuretics may not experience significant potassium depletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of potassium supplements, spironolactone of amiloride on the potassium status of patients with heart failure. Davidson, C., Burkinshaw, L., Morgan, DB.[2019]

In a study of 36 male patients with high blood pressure, potassium chloride supplementation did not significantly lower overall blood pressure but effectively prevented increases in blood pressure and pulse rate when changing posture, particularly in those with low sodium excretion.

For patients with high sodium intake, potassium chloride was found to lower both systolic and diastolic blood pressure, suggesting that potassium can mitigate the blood pressure-raising effects of sodium chloride.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of potassium in control of blood pressure. Morgan, T., Teow, BH., Myers, J.[2018]

Low dietary potassium intake is linked to the development of diseases like hypertension and possibly stomach cancer, suggesting that increasing potassium through diet could have health benefits, especially for certain populations.

Routine use of potassium-sparing diuretics alongside non-potassium-retaining diuretics for hypertension treatment is not justified, as mild hypokalaemia from diuretics does not significantly increase the risk of arrhythmias in most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium supplements and potassium-sparing diuretics. A review and guide to appropriate use. Saggar-Malik, AK., Cappuccio, FP.[2018]

In a study of ten elderly patients with idiopathic postural hypotension, potassium supplementation significantly reduced the drop in systolic blood pressure when standing, improving from a fall of 33 mmHg to 16 mmHg, indicating its efficacy in managing this condition.

Potassium therapy was well tolerated, with seven out of ten patients reporting symptomatic improvement, suggesting it is a safe and effective treatment option for postural hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium supplementation in the treatment of idiopathic postural hypotension. Heseltine, D., Thomas, T., Wilkinson, R., et al.[2019]

A study involving 10 patients with controlled hypertension showed that a salt substitute effectively maintained normal serum potassium levels over a 6-week period, demonstrating its efficacy as a potassium replacement.

Despite being safe and cost-effective, patient acceptance of the salt substitute was low, with 8 out of 10 participants preferring to return to their prescription potassium product, indicating a challenge in its adoption despite its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of salt substitutes in the treatment of diuretic-induced hypokalemia. Hueston, WJ.[2014]

In a study of 204 hospitalized patients receiving furosemide, 70.6% experienced biochemical abnormalities, with dehydration and hypotension being the most significant clinical issues attributed to the drug.

While serious toxic effects from furosemide were rare, the study highlighted the need for careful monitoring due to the high incidence of drug-induced events, which were linked to longer hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse biochemical and clinical consequences of furosemide administration. Spino, M., Sellers, EM., Kaplan, HL., et al.[2018]

Hypertensive patients on diuretics that increase potassium loss can effectively prevent low potassium levels (hypokalemia) by consuming potassium-rich foods or using liquid potassium supplements.

While slow-release potassium chloride supplements are convenient, they carry a risk of serious gastrointestinal injury, highlighting the need for careful consideration when choosing potassium supplementation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Klotrix and other slow-release potassium tablets. [2013]

Both fixed combinations of beta-blockers and diuretics (penbutolol plus furosemide and pindolol plus clopamide) were equally effective in lowering blood pressure in hypertensive outpatients, indicating similar efficacy for both treatments.

However, the pindolol-clopamide combination was associated with significant weight gain and decreased serum potassium levels, which raises safety concerns, especially for patients at risk of low potassium (hypokalemia).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum potassium and body weight during treatment with two fixed combinations of beta-blockers and diuretics in hypertensive patients: a controlled study. Houtzagers, JJ., Sumajow, CA., Chadha, DR.[2013]

In a study of 17,068 hospitalized patients, 13.9% received furosemide, primarily for congestive heart failure, indicating its common use in managing cardiovascular conditions.

While 10.1% of furosemide recipients experienced adverse reactions, serious life-threatening effects were rare, suggesting that furosemide is generally safe, especially when potassium supplements are used to mitigate hypokalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. Greenblatt, DJ., Duhme, DW., Allen, MD., et al.[2019]

In a four-year study of 533 hospitalized patients receiving furosemide, 39.8% experienced adverse reactions (ARs), with the most common being electrolyte disturbances and extracellular volume depletion, indicating a significant incidence of ARs associated with this medication.

While the overall frequency of severe ARs was low, they were notably higher in patients with liver cirrhosis, suggesting that these patients require careful monitoring when treated with furosemide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Furosemide-induced adverse reactions during hospitalization. Naranjo, CA., Busto, U., Cassis, L.[2013]

In patients with chronic kidney disease (CKD), maintaining potassium (K+) balance is crucial to prevent hyperkalemia, and this is achieved through increased kidney and gastrointestinal excretion as long as the glomerular filtration rate (GFR) is above 15-20 mL/min.

Management strategies for hyperkalemia include reviewing and potentially discontinuing medications that impair K+ excretion, educating patients about dietary sources of potassium, and using diuretics and potassium-binding drugs to help maintain safe potassium levels while allowing the continued use of beneficial medications like renin-angiotensin blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathophysiology and clinical management of hyperkalemia in chronic kidney disease. Palmer, BF., Clegg, DJ.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9957829/

an evaluation of a prescribing cascade relic Our findings confirm the high incidence of a loop diuretic-potassium supplementation prescribing cascade, with up to one–third of patients in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3989905/

Furosemide and Potassium Chloride-induced Alteration in ... The results suggest that the use of these drugs leads to proteomic alteration, which involve in cardiac conductivity that might increase the risk of SCD.

3. go.drugbank.com go.drugbank.com/drugs/DB00695

Furosemide: Uses, Interactions, Mechanism of Action Furosemide is a loop diuretic used to treat hypertension and edema in congestive heart failure, liver cirrhosis, renal disease, and hypertension.

4. eshonline.org eshonline.org/esh-content/uploads/2019/07/2.-Diuretics-in-clinical-Practice.-Part2.pdf

Diuretics in clinical practice. Part II: electrolyte and acid- ... Potassium-sparing diuretics can also induce metabolic acidosis. Mild metabolic alkalosis develops commonly during thiazide or loop diuretic treatment but is ...

5. drugs.com drugs.com/drug-interactions/furosemide-with-potassium-chloride-1146-0-1912-0.html

Furosemide and potassium chloride Interactions Furosemide and ethanol (alcohol) may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, ...

6. drugs.com drugs.com/drug-interactions/lasix-with-potassium-chloride-1146-676-1912-0.html?professional=1

Drug Interactions between Lasix and potassium chloride There were no interactions found between Lasix and potassium chloride. However, this does not necessarily mean no interactions exist. Always consult your ...

7. pdr.net pdr.net/drug-summary/Lasix-furosemide-2594

Lasix - Drug Summary Furosemide is a loop diuretic that inhibits sodium and chloride resorption by competing with chloride for the Na+/K+/2Cl- co-transporter in the ascending limb ...