Ignite Creation Date:
2024-05-06 @ 8:09 PM
Last Modification Date:
2024-10-26 @ 3:21 PM
Study NCT ID:
NCT06277336
Status:
RECRUITING
Last Update Posted:
2024-04-12
First Post:
2024-01-30
Brief Title:
Effects of Intravenous Pyr1Apelin-13 on Healthy Volunteers With Artificially Induced SIAD
Sponsor:
University Hospital Basel Switzerland
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Effects of Intravenous Pyr1Apelin-13 on Healthy Volunteers With Artificially Induced SIAD- the ESCAPE Study
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ESCAPE
Brief Summary:
Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation The study aims to investigate whether the apelin hormone which plays a role in regulating salt and water balance in the body can be used to treat hyponatremia
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water thus inducing a temporary hyponatremia state The researchers will measure the volunteers blood and urine electrolyte levels to see how these are influenced by apelin administration As comparison the same measurements will be done in volunteers dosed with placebo instead of apelin
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output If the study focused in the healthy volunteers population is successful the investigators will assess the effect of apelin administration in patients with chronic hyponatremia
The studys hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water thus inducing a temporary hyponatremia state The researchers will measure the volunteers blood and urine electrolyte levels to see how these are influenced by apelin administration As comparison the same measurements will be done in volunteers dosed with placebo instead of apelin
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output If the study focused in the healthy volunteers population is successful the investigators will assess the effect of apelin administration in patients with chronic hyponatremia
The studys hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia
Detailed Description:
Hyponatremia defined as plasma sodium levels 135 mmoll is the most frequent electrolyte and fluid disturbance with a prevalence up to 30 in hospitalized patients It is usually classified according to its duration its biochemical findings hypotonicisotonichypertonic mildmoderateprofound its symptoms severity mildmoderatesevere and volume status hypovolemiceuvolemichypervolemic Chronic hyponatremia defined as a duration 48 hours is associated with longer hospital stays and higher hospital costs increased mortality and morbidity such as gait instability falls osteoporosis fractures and attention deficit Hyponatremia is recognized as a marker of poor prognosis in multiple diseases but the extent of its causative role has not been quantified to date There is increasing evidence that correcting hyponatremia could improve clinical outcome
The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis SIAD which is also the main etiology of hyponatremia overall SIAD is characterized by an imbalanced arginine vasopressin AVP secretion or an increased renal AVP sensitivity This leads to free water retention thereupon to extracellular volume expansion and a subsequent renal sodium loss resulting in hypotonic hyponatremia Patients with SIAD are usually older adults with many comorbidities and polypharmacy making physiological studies difficult to interpret due to many possible confounders To overcome this limitation the investigators designed a protocol of artificial SIAD induction in healthy volunteers through administration of desmopressin and water loadingThis model allowed us to develop the use of the SGLT2 inhibitors empagliflozin as a promising treatment option for SIAD
The apelin receptor is a g-protein coupled receptor whose structure resembles the angiotensin 2 type 1 receptor It has two endogenous ligands apelin and elabela whose different isoforms are present in different organs and are thought to work in an autocrineparacrine manner Apelin is inter alia expressed in the magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei together with AVP and oxytocin
Apelin has a broad spectrum of beneficial physiological effects and thus represents an attractive new target in many medical fields For instance it naturally displays vasodilatatory and inotropic effects and promotes glucose uptake and lipolysis In salt and water homeostasis apelin counteracts the effects of AVP by inhibiting central AVP release and AVP renal effect as well as by antagonizing the vasoconstrictive effects of angiotensin II on renal afferent arterioles and increasing renal blood flow
AVP and apelin have been shown to change in opposite directions upon hypo- and hyperosmotic challenges in healthy humans A cross-sectional study in hyponatremic patients with SIAD or heart failure suggests that not only an increased copeptin surrogate stoichiometric marker of AVP but also relative insufficient apelin levels contribute to renal water reabsorption in hyponatremia Re-establishing a physiological copeptin apelin ratio by administering exogenous apelin could therefore restore a normal salt and water balance This concept was tested in hyponatremic rats in which an apelin-17 analog increased urine output decreased urine osmolality and increased sodium levels to a similar extent as tolvaptan These results suggest that apelin could become an effective treatment for SIAD once a long-acting analog will be developed for human use However whether a similar effect could be induced in humans is still not known and needs to be investigated in order to characterize apelin physiology in disorders of salt and water balance
The investigators therefore hypothesize that the administration of intravenous Pyr1apelin-13 the most common apelin isoform in the blood increases urinary excretion and thus sodium levels in healthy participants with artificially induced SIAD In case the hypothesis is confirmed the investigators aim to investigate the physiological effect of intravenous Pyr1apelin-13 administration in hyponatremic patients with chronic SIAD
The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis SIAD which is also the main etiology of hyponatremia overall SIAD is characterized by an imbalanced arginine vasopressin AVP secretion or an increased renal AVP sensitivity This leads to free water retention thereupon to extracellular volume expansion and a subsequent renal sodium loss resulting in hypotonic hyponatremia Patients with SIAD are usually older adults with many comorbidities and polypharmacy making physiological studies difficult to interpret due to many possible confounders To overcome this limitation the investigators designed a protocol of artificial SIAD induction in healthy volunteers through administration of desmopressin and water loadingThis model allowed us to develop the use of the SGLT2 inhibitors empagliflozin as a promising treatment option for SIAD
The apelin receptor is a g-protein coupled receptor whose structure resembles the angiotensin 2 type 1 receptor It has two endogenous ligands apelin and elabela whose different isoforms are present in different organs and are thought to work in an autocrineparacrine manner Apelin is inter alia expressed in the magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei together with AVP and oxytocin
Apelin has a broad spectrum of beneficial physiological effects and thus represents an attractive new target in many medical fields For instance it naturally displays vasodilatatory and inotropic effects and promotes glucose uptake and lipolysis In salt and water homeostasis apelin counteracts the effects of AVP by inhibiting central AVP release and AVP renal effect as well as by antagonizing the vasoconstrictive effects of angiotensin II on renal afferent arterioles and increasing renal blood flow
AVP and apelin have been shown to change in opposite directions upon hypo- and hyperosmotic challenges in healthy humans A cross-sectional study in hyponatremic patients with SIAD or heart failure suggests that not only an increased copeptin surrogate stoichiometric marker of AVP but also relative insufficient apelin levels contribute to renal water reabsorption in hyponatremia Re-establishing a physiological copeptin apelin ratio by administering exogenous apelin could therefore restore a normal salt and water balance This concept was tested in hyponatremic rats in which an apelin-17 analog increased urine output decreased urine osmolality and increased sodium levels to a similar extent as tolvaptan These results suggest that apelin could become an effective treatment for SIAD once a long-acting analog will be developed for human use However whether a similar effect could be induced in humans is still not known and needs to be investigated in order to characterize apelin physiology in disorders of salt and water balance
The investigators therefore hypothesize that the administration of intravenous Pyr1apelin-13 the most common apelin isoform in the blood increases urinary excretion and thus sodium levels in healthy participants with artificially induced SIAD In case the hypothesis is confirmed the investigators aim to investigate the physiological effect of intravenous Pyr1apelin-13 administration in hyponatremic patients with chronic SIAD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None