Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD

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 study's hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia.

Conditions

• SIAD - Syndrome of Inappropriate Antidiuresis
• Hyponatremia

Interventions

DRUG

Placebo

Artificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h)

DRUG

Apelin Low Dose

Artificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml infusion of \[Pyr1\]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 1 nmol/min (60ml per h)

DRUG

Apelin High Dose

Artificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml infusion of \[Pyr1\]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 10 nmol/min (60ml per h)

DRUG

Selected Apelin Dose

Study infusions (timepoint 0 to timepoint +3): * 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h) * 180-ml infusion of \[Pyr1\]apelin-13 in NaCl 0.45% over 3 hours based on the best performing apelin dose (from Low Dose or High Dose) in healthy volunteers corresponding to one of the following options: 1. at an infusion rate of 1 nmol/min (60ml per h) OR 2. at an infusion rate of 10 nmol/min (60ml per h) In case both apelin dosis performed equally well in the healthy volunteers population the lower dose will be selected.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland

  lead OTHER

Principal Investigators

• Mirjam Christ-Crain, Prof. Dr. · University Hospital Basel; Endocrinology, Diabetes and Metabolism

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-03-01

Primary Completion

2025-03-18

Completion

2025-03-18

Countries

• Switzerland

Study Locations