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

Trial Summary

What is the purpose of this trial?

The purpose of Lunar OI (Orthostatic Intolerance) is to determine if there are differences between males and females in tolerance to and cardiovascular responses during different angles of head-up tilt simulating gravity levels less than or equal to Earth's gravity. Also, this study will determine if a gradient compression garment affects tolerance to tilting and the cardiovascular stress at different tilt angles. Males and females are being identified by biological sex. This will be a two-phased study design. In Phase I we will determine whether there are differences in the development of signs or symptoms of orthostatic intolerance between males and females when tilted head up on a table to different angles to simulate gravity levels that astronauts may experience when landing on or launching from the surface of the Moon. In Phase II, the tilt tests simulating the same gravity levels from Phase I will be repeated, but a custom-made lower-body compression garment will be worn to see if wearing the garment affects the development of orthostatic intolerance. For both study phases, before tilting, a drug will be administered to reduce the amount fluid in the blood (plasma) to levels similar to that experienced by astronauts during spaceflight.

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 data supports the effectiveness of potassium supplements as a treatment for orthostatic intolerance?

Research shows that potassium supplements can help reduce the drop in blood pressure when standing up, which is a key issue in orthostatic intolerance. In a study, patients experienced a significant decrease in the fall of blood pressure when taking potassium, and many reported feeling better. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Furosemide is generally considered safe, but it can cause side effects like dehydration and low potassium levels, especially at higher doses or in patients with liver disease. Potassium supplements and salt substitutes are also safe, but some people may not like the taste of salt substitutes. ^{6 7 8 9 10}

How does the drug Furosemide with Potassium Supplement differ from other treatments for orthostatic intolerance?

This drug combination is unique because it uses potassium supplements to help manage blood pressure changes when standing, which is a key issue in orthostatic intolerance. Potassium can help stabilize blood pressure and prevent the drop that occurs when standing, making it a potentially effective and safe option for treating this condition. ^{1 2 3 5 11}

Eligibility Criteria

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.

I have a condition or take medication that affects my heart.

Known allergy to furosemide or sulfa drugs

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Potassium supplementation in the treatment of idiopathic postural hypotension. [2019]

2. England pubmed.ncbi.nlm.nih.gov

The effects of potassium supplements, spironolactone of amiloride on the potassium status of patients with heart failure. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

The role of potassium in control of blood pressure. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

Potassium supplements and potassium-sparing diuretics. A review and guide to appropriate use. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Furosemide-induced adverse reactions during hospitalization. [2013]

9. Italy pubmed.ncbi.nlm.nih.gov

Pathophysiology and clinical management of hyperkalemia in chronic kidney disease. [2023]

10. Canada pubmed.ncbi.nlm.nih.gov

Adverse biochemical and clinical consequences of furosemide administration. [2018]

11. United States 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. [2013]