Vasopressin in the Elderly: Physiological Changes in Neuroendocrine Function and Urinary Secretion in Healthy Aging (VENUS)

Elderly people are at a high risk for disturbances in water homeostasis, with both hypo- and hypernatremia being more common with increasing age. Several changes in the physiology of the ageing body are responsible for this predisposition towards hypo- and hypernatremia, including diminished thirst perception, decreasing kidney function, and altered body composition. In addition, age-related changes in AVP secretion have been suggested, but findings remain inconclusive. Possibly, this controversy is due to measurement challenges of AVP.

Copeptin, a surrogate marker of AVP-release, is more stable and a reliable assay is commercially available. While copeptin stimulation and suppression has been studied in healthy volunteers, no study assessed possible changes in copeptin dynamics occurring with ageing.

Therefore, the aim of this study is to investigate copeptin levels in hypo- and hyperosmolar states in generally healthy elderly adults compared to young controls. The investigators hypothesize that both the suppression and stimulation of copeptin is impaired and that the overall range of variation is diminished with increasing age.

This is a monocentric open-labeled randomized controlled trial conducted at the university hospital Basel. All participants will be scheduled for a copeptin stimulation test using hypertonic saline infusion and a copeptin suppression test using water ingestion. The order of the two study visits will be randomized at study inclusion.

Study Overview

• Status: Completed
• Conditions: Healthy Ageing
• Intervention / Treatment: Other: Hypertonic 3% saline; Other: Water

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-30 years or ≥ 60 years
• Normonatremia (135-145 mmol/L)
• Plasma osmolality 280-300 mOsm/kg
• BMI ≥18 and ≤ 30 kg/m2

Exclusion Criteria:

• Regular use of medication with effects on water homeostasis (e.g. blood pressure medication, neuroleptics, desmopressin, etc.)
• Any severe disease requiring frequent medical care, except physiotherapy and/or psychotherapy
• Pacemaker or ICD
• History of thrombosis
• Active oncologic disease
• Heart failure
• Liver cirrhosis
• Estimated glomerular filtration rate (eGFR) < 60 ml/kg/1.73 m2
• Uncontrolled hypertension >160 mmHg systolic or >100 mmHg diastolic
• Polydipsia (ingestion of >3L fluids per day) and polyuria (>50 ml/kg urine production within 24 hours)
• Pregnancy or breastfeeding
• Participation in a study with investigational drugs within 30 days
• Acute illness
• Inability to follow study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation first, Suppression second	Other: Hypertonic 3% saline; Participants receive 10 ml/kg body weight of 3% saline infused over 1 hour. The aim is to stimulate copeptin release.; Other: Water; Participants ingest 20 ml/kg water over 1h. The aim is to suppress copeptin release.
Experimental: Suppression first, Stimulation second	Other: Hypertonic 3% saline; Participants receive 10 ml/kg body weight of 3% saline infused over 1 hour. The aim is to stimulate copeptin release.; Other: Water; Participants ingest 20 ml/kg water over 1h. The aim is to suppress copeptin release.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Range of Variation in Copeptin	The primary outcome is the range of variation in copeptin, i.e. difference of suppressed copeptin to the stimulated copeptin, in healthy elderly participants compared to young controls.	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in Copeptin upon stimulation and suppression	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Differences in total body water (L) measured by body impedance analysis	at Baseline
Changes in cortisol (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in blood pressure (mmHg)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in heart rate	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma sodium (mmol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma potassium (mmol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma chloride (mmol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma osmolality (mOsm/kg)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in estimated glomerular filtration rate (ml/kg/1.73m2)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma glucose (mmol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma urea (mmol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in plasma uric acid (umol/L)	Baseline, 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine osmolality (mOsm/kg)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine sodium (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine potassium (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine chloride (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine urea (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine uric acid (umol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine glucose (mmol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion
Changes in urine creatinine (umol/L)	Baseline, 60 minutes, and 120 minutes both after saline administration and after water ingestion

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2025
• Primary Completion (Actual): October 10, 2025
• Study Completion (Actual): October 10, 2025

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Inorganic Chemicals; Chlorine Compounds; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Oxides; Oxygen Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Water; Sodium Chloride
• Other Study ID Numbers: 2025-00474

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No