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

NCT06277336 | Completed

• 1 other identifier: 2023-01716; kt23ChristCrain3
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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 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

Keywords

Apelin

Outcome Measures

Primary Outcomes (1)

• Total urinary excretion (ml)

  Urinary excretion, in ml, between end of water loading and one hour past study infusion completion

  assessment between timepoint 0 hours and timepoint +4 hours

Secondary Outcomes (6)

• Hourly and total urinary excretion (ml)

  assessment between timepoint -2 hours and timepoint +9 hours

• Change in electrolyte free water clearance (ml/min)

  assessment between timepoint -2 hours and timepoint +9 hours

• Change in free water clearance (ml/min)

  assessment between timepoint -2 hours and timepoint +9 hours

• Change in plasma osmolality (mOsm/kg)

  assessment between baseline and timepoint +9 hours

• Change in plasma sodium (mmol/l)

  assessment between baseline and timepoint +9 hours

Study Arms (8)

Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed.

Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose

Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.

Drug: Placebo; Drug: Selected Apelin Dose

Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo

EXPERIMENTAL

The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.

Drug: Placebo; Drug: Selected Apelin Dose

Interventions

Placebo DRUG

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)

Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose; Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo; Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose; Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose; Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose; Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose

Apelin Low Dose DRUG

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)

Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose; Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose; Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose; Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose

Apelin High Dose DRUG

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)

Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo; Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose; Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose; Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose; Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose

Selected Apelin Dose DRUG

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.

Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose; Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• Age 18 to 65 years
• Serum sodium level 135-145mmol/l
• Clinically euvolemic status
• For female only: Due to the influence of estrogen on apelin levels, only females with combined (=containing estrogen) oral contraceptive pill will be included in order to guarantee a similar estrogen levels at each visit.

You may not qualify if:

• Known or suspected allergy to trial product or related products or history of multiple and/or severe allergic reaction to drugs (including study drugs) or food
• Pregnancy, wish to become pregnant during study period or breastfeeding
• Overt cardiovascular disease or abnormality in screening ECG
• Family history of sudden cardiac death or unexplained sudden death \< 50 years
• Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome) or personal history/active malignant disease
• Hepatic impairment (ALAT/ASAT \>3x upper limit) or liver cirrhosis
• Kidney disease (GFR \< 60ml/min)
• History of epileptic seizures
• Diabetes mellitus type 1 or 2
• Other severe disease requiring regular medication intake or regular medical care
• Any daily medication (including vitamin supplements).
• Uncontrolled hypertension (systolic blood pressure \>160mmHg or diastolic blood pressure \>100 mmHg)
• BMI \<18 or \>29kg/m2
• Inability to follow the procedures of the study (e.g. due to language problems, psychological disorders, dementia).
• Participation in another study with an investigational drug within the 30 days preceding and during the present study.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Inappropriate ADH Syndrome; Hyponatremia

Interventions

Apelin

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Mirjam Christ-Crain, Prof. Dr.

  University Hospital Basel; Endocrinology, Diabetes and Metabolism

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 26, 2024
• Study Start: March 1, 2024
• Primary Completion: March 18, 2025
• Study Completion: March 18, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)