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CompletedNCT03422848H2O-metabolismUpdated Dec 2, 2025

Hydration to Optimize Metabolism

An interventional study of Water and general life style advice in Glucose, High Blood, sponsored by Region Skane. Completed at 1 site in Sweden. Open to participants aged 20 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-02.

Sponsored by Region Skane · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
797
Allocation
Randomized
Ages
20 Years to 75 Years
Sex
All
01

Study summary

This study evaluates hydration (1.5 L of water daily during 1 year) in the lowering of blood glucose concentration in adults with signs of dehydration (elevated levels of the vasopressin marker copeptin and high urine osmolality). Half of participants will in addition to lifestyle advice receive extra water on top of their habitual fluid intake, and the other half (control) will receive only lifestyle advice.

Read the detailed description

High plasma concentration of vasopressin (i.e. antidiuretic hormone) is a novel and independent risk factor for type 2 diabetes, the metabolic syndrome, cardiovascular disease and premature death. The main physiological role of vasopressin is to maintain constant plasma osmolality. Previous studies in rats and mendelian randomization studies in humans suggest causality between elevated vasopressin concentration and elevated plasma glucose concentration. As vasopressin can be suppressed by increasing water intake, we hypothesize that water supplementation in individuals with high vasopressin can lower plasma glucose and prevent diabetes.

The aim of this project is to test in a single-centre randomized clinical trial (RCT), if water supplementation in subjects with high plasma levels of vasopressin (measured by a stable vasopressin marker of its precursor hormone called copeptin) can reduce fasting levels of glucose (primary outcome measure), risk of new-onset diabetes and other cardiometabolic risk factors (secondary outcome measures).

02

Conditions studied

  • Glucose, High Blood

Keywords

  • hydration
  • water
  • vasopressin
  • copeptin
  • glucose
  • OGTT
  • insulin
  • glucagon
03

Who can participate

Ages eligible
20 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Provision of informed consent, age 20-75 years with high plasma concentration of vasopressin (plasma concentration of copeptin of > 6.1 pmol/L in women and > 10.7 pmol/L in men) and 24 hour urine osmolality > 600 milliosmol (mOsm) /kg water.

Exclusion criteria

Exclusion Criteria:

  • 24 hour urine volume > 1.5 L, pregnancy or breastfeeding, plasma sodium \< 135 mmol/L, use of diuretics, lithium or selective serotonin reuptake inhibitor (SSRI) drugs, chronic kidney disease (estimated glomerular filtration rate \< 30 mL/min), heart failure, inflammatory bowel disease, type 1 diabetes or type 2 diabetes treated with insulin, vulnerable subjects (subjects with legal guardian, with loss of personal liberty).
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
797 participants (actual)

Study arms

  • Active comparator
    Water intervention arm

    The water intervention group will increase their habitual daily water intake with 1.5 L of tap water. Furthermore they will receive general life style advice (general oral and written advice on diet and physical activity).

    Dietary Supplement: Water · Behavioral: general life style advice

  • Other
    Control arm

    Control group that will receive general life style advice (general oral and written advice on diet and physical activity).

    Behavioral: general life style advice

Interventions

  • Dietary supplementWater

    Increased daily water intake with 1.5 L of water on top of habitual water intake.

  • Behavioralgeneral life style advice

    oral and written advice on diet and physical activity

05

What researchers measure

Primary outcomes

  1. Fasting plasma glucose concentration (mmol/L)

    Difference in change of fasting plasma glucose between water intervention arm and control arm.

    Time frame: 12 months

Secondary outcomes

  1. Diabetes incidence

    Difference in diabetes incidence between water intervention arm and control arm.

    Time frame: 12 months

  2. Post oral glucose load glucose concentration (mmol/L)

    Difference in change of post oral glucose load glucose concentration (mmol/L) between water intervention arm and control arm

    Time frame: 12 months

  3. Fasting insulin concentration (mIE/L)

    Difference in change of fasting insulin (mIE/L) between water intervention arm and control arm

    Time frame: 12 months

  4. Post oral glucose load insulin concentration (mIE/L)

    Difference in change of post oral glucose load insulin concentration (mIE/L) between water intervention arm and control arm

    Time frame: 12 months

  5. Fasting glucagon concentration (pmol/L)

    Difference in change of fasting glucagon (pmol/L) between water intervention arm and control arm

    Time frame: 12 months

  6. Post oral glucose load glucagon concentration (pmol/L)

    Difference in change of post oral glucose load glucagon concentration (pmol/L) between water intervention arm and control arm

    Time frame: 12 months

  7. HbA1c concentration (mmol/mol)

    Difference in change of HbA1c (mmol/mol) between water intervention arm and control arm

    Time frame: 12 months

  8. Waist circumference (cm)

    Difference in change of waist circumference (cm) between water intervention arm and control arm

    Time frame: 12 months

  9. Body mass index (kg/m^2)

    Difference in change of body mass index (kg/m\^2) between water intervention arm and control arm

    Time frame: 12 months

  10. Systolic blood pressure (mmHg)

    Difference in change of systolic blood pressure (mmHg) between water intervention arm and control arm

    Time frame: 12 months

  11. Diastolic blood pressure (mmHg)

    Difference in change of diastolic blood pressure (mmHg) between water intervention arm and control arm

    Time frame: 12 months

  12. Triglyceride concentration (mmol/L)

    Difference in change of triglycerides (mmol/L) between water intervention arm and control arm

    Time frame: 12 months

  13. HDL cholesterol concentration (mmol/L)

    Difference in change of HDL cholesterol (mmol/L) between water intervention arm and control arm

    Time frame: 12 months

  14. LDL cholesterol concentration (mmol/L)

    Difference in change of LDL cholesterol (mmol/L) between water intervention arm and control arm

    Time frame: 12 months

  15. Apolipoprotein B concentration (g/L)

    Difference in change of Apolipoprotein B (g/L) between water intervention arm and control arm

    Time frame: 12 months

  16. Apolipoprotein A1 concentration (g/L)

    Difference in change of Apolipoprotein A1 (g/L) between water intervention arm and control arm

    Time frame: 12 months

  17. Urine albumin/creatinine ratio (g/mol)

    Difference in change of urine albumin/creatinine ratio (g/mol) between water intervention arm and control arm

    Time frame: 12 months

  18. Estimated glomerular filtration rate (mL/min/1,73 m2)

    Difference in change of estimated glomerular filtration rate (mL/min/1,73 m2) between water intervention arm and control arm

    Time frame: 12 months

  19. Creatinine clearance (mL/min)

    Difference in change of creatinine clearance (mL/min) between water intervention arm and control arm

    Time frame: 12 months

  20. Fasting cortisol concentration (nmol/L)

    Difference in change of fasting cortisol (nmol/L) between water intervention arm and control arm

    Time frame: 12 months

  21. Fasting adrenocorticotropic hormone concentration (pmol/L)

    Difference in change of fasting adrenocorticotropic hormone (pmol/L) between water intervention arm and control arm

    Time frame: 12 months

  22. C-reactive protein concentration (mg/L)

    Difference in change of C-reactive protein (mg/L) between water intervention arm and control arm

    Time frame: 12 months

  23. Hair cortisol concentration (pg/mg)

    Difference in change of hair cortisol (pg/mg) between water intervention arm and control arm. Hair cortisol is a measure of chronic stress exposure 3 months prior to sampling.

    Time frame: 12 months between samplings

Other outcomes

  1. Fasting plasma glucose concentration in pre-specified subgroups

    glucose reduction in A) subjects who remain high in copeptin from population screening to main study baseline, B) subjects with the highest (top tertile) baseline copeptin, C) subjects with/without diabetes mellitus at baseline, D) subjects with/without impaired fasting glucose (diabetes+impaired/not impaired), E) men and women separately.

    Time frame: 12 months

06

Study locations

1 site
  • KFE, Skåne University Hospital in Malmö
    Malmö, SE-20502, Sweden
07

References and documents

Study documents

  • Study protocol · Dec 15, 2017
  • Statistical analysis plan · Dec 15, 2017
  • Statistical analysis plan · May 19, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03422848
Lead sponsor
Region Skane
Collaborators
Lund University, Danone Global Research & Innovation Center
Responsible party
Olle Melander (Professor, Region Skane) — Principal investigator
First posted
Feb 6, 2018
Start date
Apr 24, 2018
Primary completion
Dec 23, 2024
Completion
Nov 3, 2025
Last update
Dec 2, 2025

Study contacts

Olle Melander, M.D., Prof.
principal investigator · Lund University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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