Treatments for Orthostatic Intolerance
(Lunar OI Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
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.
12345Is 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.
678910How 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.
123511Eligibility 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
+3 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Hypovolemic plus garmentExperimental Treatment3 Interventions
Furosemide and potassium supplement plus OIG.
Group II: HypovolemicExperimental Treatment2 Interventions
Furosemide and potassium supplement.
Group III: ControlActive Control1 Intervention
Furosemide is already approved in European Union, United States, Canada, Japan, China for the following indications:
πͺπΊ Approved in European Union as Lasix for:
- Hypertension
- Edema associated with congestive heart failure
- Liver cirrhosis
- Renal disease
- Nephrotic syndrome
πΊπΈ Approved in United States as Lasix for:
- Edema associated with congestive heart failure
- Liver cirrhosis
- Renal disease
- Nephrotic syndrome
- Acute pulmonary edema
π¨π¦ Approved in Canada as Lasix for:
- Edema associated with congestive heart failure
- Liver cirrhosis
- Renal disease
- Nephrotic syndrome
- Hypertension
π―π΅ Approved in Japan as Lasix for:
- Edema associated with congestive heart failure
- Liver cirrhosis
- Renal disease
- Nephrotic syndrome
π¨π³ Approved in China as Lasix for:
- Edema associated with congestive heart failure
- Liver cirrhosis
- Renal disease
- Nephrotic syndrome
- Hypertension
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NASAHouston, TX
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Who Is Running the Clinical Trial?
National Aeronautics and Space Administration (NASA)Lead Sponsor
References
Potassium supplementation in the treatment of idiopathic postural hypotension. [2019]We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.
The effects of potassium supplements, spironolactone of amiloride on the potassium status of patients with heart failure. [2019]Extra potassium supplements, spironolactone or amiloride were given for 5 months to forty-nine patients with heart failure who were taking furosemide and were in a steady state. Plasma potassium increased with all three treatments but there was no significant increase in total body potassium or red cell potassium. These findings together with other studies suggest that patients with heart failure taking diuretics do not have a significant depletion of body potassium.
The role of potassium in control of blood pressure. [2018]Extra potassium intake has been found to be a determinant of blood pressure for epidemiological and experimental reasons. People with hypertension have a small fall in blood pressure with added potassium. Potassium chloride (48 mmol/day) was given to 36 male patients with high blood pressure; 5 did not comply with therapy. In the entire group of patients, potassium chloride had no significant effect on blood pressure, but prevented the rise in blood pressure and pulse rate produced by posture. In patients with a urinary Na+ excretion less than 75 mmol per 10 mmol creatinine, potassium chloride had no effect on supine blood pressure, but prevented the rise in blood pressure and pulse rate with standing. In those on a high sodium intake, potassium chloride lowered both the systolic and diastolic pressures. In sodium-responsive subjects, potassium chloride prevented the rise in blood pressure induced by sodium chloride but had no significant effect on blood pressure when on a low sodium intake. These results indicate that potassium reduces the rise in blood pressure caused by sodium chloride and reduces the increased sympathetic postural response seen in people on a low sodium intake.
Klotrix and other slow-release potassium tablets. [2013]Most hypertensive patients who take diuretics that increase potassium excretion can avoid hypokalemia by eating foods high in potassium or taking liquid potassium supplements. Slow-release preparations of potassium chloride are convenient but can cause serious gastrointestinal injury.
Potassium supplements and potassium-sparing diuretics. A review and guide to appropriate use. [2018]Epidemiological and clinical studies suggest that low dietary potassium intake may have an important role in determining the development of diseases such as hypertension, and perhaps even stomach cancer, and that increased potassium intake may have beneficial effects in several other conditions. Dietary adjustment or active potassium supplementation has been suggested as a natural, less costly and safe method of increasing potassium levels, although active supplementation with tablets or solutions is not recommended in healthy people with normal serum potassium levels. However, increasing dietary potassium intake in the elderly and in patients with renal impairment must be considered with caution. Diuretics have a long established role in the management of hypertension and heart failure. There is no convincing evidence to suggest that the small reduction in plasma potassium levels associated with low dose thiazide and loop diuretic therapy needs to be routinely prevented by the use of potassium-sparing drugs. In non-digitalised patients little association has been found between mild diuretic-induced hypokalaemia and arrhythmias. Thus, the routine prophylactic use of potassium-sparing diuretics in combination with non-potassium-retaining diuretics for the treatment of hypertension and oedematous states is not justified. Based on current evidence, treating all patients whose serum potassium level decreases below 3 mmol/L is recommended, although for certain patients at particular risk of hypokalaemia, levels may need to be maintained above 3.5 mmol/L. In overt hypokalaemia, several therapeutic options are available to the clinician. These include increased consumption of potassium-rich foods, the use of salt substitutes, medicinal potassium supplementation or distal tubular (potassium-sparing) diuretics.
Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. [2019]Of 17,068 hospitalized medical patients monitored in a drug surveillance program, 2,367 (13.9 per cent) received furosemide. Of these patients, 53 per cent were hospitalized with a primary (first) diagnosis of cardiovascular disease; many other patients had cardiovascular disorders coincident with other diseases. In 78 per cent of cases the indication for furosemide therapy was congestive heart failure. Adverse reactions were attributed to furosemide in 239 patients (10.1 per cent), but in only 14 instances were the unwanted effects considered life-threatening. The most common adverse reactions were: intravascular volume depletion (4.6 per cent of furosemide recipients), hypokalemia (3.6 per cent), and other eletrolyte disturbances (1.5 per cent). Many patients experienced more than one manifestation of toxicity. The over-all frequency of adverse reactions increased progressively with higher daily doses of furosemide, but was not correlated with total furosemide dose. Among furosemide recipients who also recieved potassium-supplements or potassium-sparing diuretics, hypokalemia was less frequent, less severe, and of slower onset. Coadministration of other diuretics with furosemide was associated with a higher frequency of volume depletion. The findings indicate that furosemide is a relatively safe diuretic in a wide range of clinical situations. Serious adverse reactions are uncommon, and occur primarily in the seriously ill.
Use of salt substitutes in the treatment of diuretic-induced hypokalemia. [2014]To evaluate the safety, effectiveness, and patient acceptance of salt substitutes for use as a potassium replacement, a series of 10 patients who had controlled hypertension and who were taking a prescription potassium replacement product for diuretic-induced hypokalemia agreed to switch from their usual potassium product to the salt substitute for 6 weeks. Serum potassium values were monitored every 2 weeks while patients took the salt substitute. It was found that the salt substitute was very effective at maintaining patients' serum potassium in the normal range. A questionnaire completed at the end of the 6-week period showed that only three patients experienced any side effects from the salt substitute, none of which was severe enough to warrant discontinuation of the product. The questionnaire also revealed, however, that patients did not care for the salt substitute, and at the end of the study, eight out of the 10 subjects chose to return to their prescription potassium product despite a marked cost advantage in favor of the salt substitute. While this study shows that salt substitutes are an effective, safe, and economical alternative to prescription potassium products, poor patient acceptance of this agent is discouraging. acceptance
Furosemide-induced adverse reactions during hospitalization. [2013]The frequency and types of adverse reactions (ARs) occurring in hospitalized patients receiving furosemide were surveyed prospectively in a four-year study at the JosΓ© Joaquin Aquirre Hospital in Santiago, Chile. A team of clinical pharmacists and clinical pharmacologists monitored 533 patients receiving furosemide and recorded patient characteristics, laboratory test results, drugs administered, and suspected ARs. Definite or probably furosemide-induced ARs were detected in 220 (39.8%) patients. No ARs were fatal but 7.6% of patients, all having cirrhosis of the liver, had severe ARs. Of the ARs recorded, 95.2% were dose-related. The most common ARs were electrolyte disturbances (23.5% of patients), extracellular volume depletion (9.0% of patients) and hepatic comma (3.6% of patients). Total and daily furosemide doses, lengthened hospitalization and hepatic disease were significantly associated with the frequency of ARs (p less than 0.001). The dosage of furosemide did not account for the increased frequency of ARs in patients with hepatic disease. The frequency of hypokalemia was not reduced significantly when furosemide was administered with potassium chloride or potassium-sparing diuretics (p less than 0.05). The frequency of severe furosemide-induced ARs is low, but ARs are more common in patients with cirrhosis of the liver. These patients should be closely monitored for furosemide-induced ARs.
Pathophysiology and clinical management of hyperkalemia in chronic kidney disease. [2023]Adaptive increases in kidney and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with chronic kidney disease (CKD) as long as the glomerular filtration rate (GFR) remains >15-20 mL/min. K+ balance is maintained by increased secretion per functioning nephron, which is mediated by elevated plasma K+ concentration, aldosterone, increased flow rate, and enhanced Na+-K+-ATPase activity. Fecal losses of potassium also increase in CKD. These mechanisms are effective in preventing hyperkalemia if urine output is in excess of 600 mL/day and the GFR exceeds 15 mL/min. Development of hyperkalemia with only mild to moderate reductions in GFR should prompt a search for intrinsic disease of the collecting duct, disturbances in mineralocorticoid activity, and/or decreased delivery of sodium to the distal nephron. The initial approach to treatment is to review the patient's medication profile and whenever possible discontinue drugs that impair kidney K+ excretion. Patients should be educated on sources of K+ in the diet and should be strongly encouraged to avoid the use of K+ containing salt substitutes as well as herbal remedies since herbs may be a hidden source of dietary K+. Effective diuretic therapy and correction of metabolic acidosis are effective strategies to minimize the potential for hyperkalemia. Discontinuation or use of submaximal doses of renin-angiotensin blockers should be discouraged given the cardiovascular protective effect these drugs provide. Potassium binding drugs can be useful to enable use of these drugs and potentially allow liberalization of the diet in CKD patients.
Adverse biochemical and clinical consequences of furosemide administration. [2018]Nurse monitors collected clinical and laboratory data from 204 hospitalized patients receiving furosemide (122 men and 82 women; mean age 69.6 years). Biochemical abnormalities and clinical problems definitely or probably induced by any drug occurred in 70.6% and 49.0% respectively of the patients, and were attributed to furosemide in 81.3% and 13.0% respectively of these patients. The most important clinical events were dehydration and hypotension. Furosemide-induced hypochloremia, hypokalemia and hyponatremia occurred in 35.8%, 25.0% and 24.5% of the patients respectively. Most of the biochemical changes were slight, and only 3.9% of the patients had a furosemide-induced decrease in the serum potassium concentration to less than 3.0 mmol/L. Surprisingly, 24.5% of the patients also manifested drug-induced hyperkalemia. Administration potassium supplements or spironolactone, or both, concurrently with furosemide was responsible in most cases for the development of hyperkalemia. The occurrence of drug-induced adverse effects after 2 weeks of hospitalization was significantly associated (P less than 0.05) with subsequent prolongation of hospitalization. The high frequency of drug-induced events warrants careful monitoring of all patients receiving furosemide in spite of the low frequency of serious toxic effects produced by the drug.
Serum potassium and body weight during treatment with two fixed combinations of beta-blockers and diuretics in hypertensive patients: a controlled study. [2013]Two fixed combinations of beta-blockers and diuretics, penbutolol plus furosemide and pindolol plus clopamide, were compared with respect to efficacy, safety, and tolerability in hypertensive out-patients. The two preparations were equally effective in reducing blood pressure when given as a single daily dose. Doubling the dosage for those patients who responded poorly did not improve therapeutic response. The group treated with pindolol-clopamide had a significant increase in mean body weight and a substantial decrease in serum potassium concentrations. No direct relationship between these findings could be demonstrated, but the loss of potassium would be an important consideration when treating patients who are particularly vulnerable to the consequences of hypokalemia.