Clinical trial NCT03422848: Hydration to Optimize Metabolism
Official title: Hydration to Optimize Metabolism
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Glucose, High Blood
Keywords: hydration
water
vasopressin
copeptin
glucose
OGTT
insulin
glucagon
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
name: Danone Global Research & Innovation Center
First posted: 2018-02-06
Enrollment: 760
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel-group RCT with two arms during 12 months. Subjects will be randomized to the water-intervention (in total 1.5 L increment daily on the top of habitual intake) and control groups (1:1) by computer-generated block randomization. Both groups will receive general life style advice (general oral and written advice on diet and physical activity).
Primary purpose: PREVENTION

Brief 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.

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).

Eligibility criteria: 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:

* 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).

Primary outcomes:
measure: Fasting plasma glucose concentration (mmol/L)
timeFrame: 12 months
Secondary outcomes:
measure: Diabetes incidence
timeFrame: 12 months
measure: Post oral glucose load glucose concentration (mmol/L)
timeFrame: 12 months
measure: Fasting insulin concentration (mIE/L)
timeFrame: 12 months
measure: Post oral glucose load insulin concentration (mIE/L)
timeFrame: 12 months
measure: Fasting glucagon concentration (pmol/L)
timeFrame: 12 months
measure: Post oral glucose load glucagon concentration (pmol/L)
timeFrame: 12 months
measure: HbA1c concentration (mmol/mol)
timeFrame: 12 months
measure: Waist circumference (cm)
timeFrame: 12 months
measure: Body mass index (kg/m^2)
timeFrame: 12 months
measure: Systolic blood pressure (mmHg)
timeFrame: 12 months
measure: Diastolic blood pressure (mmHg)
timeFrame: 12 months
measure: Triglyceride concentration (mmol/L)
timeFrame: 12 months
measure: HDL cholesterol concentration (mmol/L)
timeFrame: 12 months
measure: LDL cholesterol concentration (mmol/L)
timeFrame: 12 months
measure: Apolipoprotein B concentration (g/L)
timeFrame: 12 months
measure: Apolipoprotein A1 concentration (g/L)
timeFrame: 12 months
measure: Urine albumin/creatinine ratio (g/mol)
timeFrame: 12 months
measure: Estimated glomerular filtration rate (mL/min/1,73 m2)
timeFrame: 12 months
measure: Creatinine clearance (mL/min)
timeFrame: 12 months
measure: Fasting cortisol concentration (nmol/L)
timeFrame: 12 months
measure: Fasting adrenocorticotropic hormone concentration (pmol/L)
timeFrame: 12 months
measure: C-reactive protein concentration (mg/L)
timeFrame: 12 months
measure: Hair cortisol concentration (pg/mg)
timeFrame: 12 months between samplings
Other outcomes:
measure: Fasting plasma glucose concentration in pre-specified subgroups
timeFrame: 12 months
Locations:
city: Malmö
country: Sweden
facility: KFE, Skåne University Hospital in Malmö
Study officials:
affiliation: Lund University
name: Olle Melander, M.D., Prof.
role: PRINCIPAL_INVESTIGATOR
References: