Determinants of thiazide induced hyponatraemia in pre-exposed elderly - a controlled experiment

ISRCTN	ISRCTN38727701
DOI	https://doi.org/10.1186/ISRCTN38727701
Protocol serial number	N/A
Sponsor	Academic Medical Centre (AMC) (The Netherlands)
Funder	Dutch Kidney Foundation (Nierstichting Nederland) (The Netherlands)

Submission date: 16/07/2007
Registration date: 16/07/2007
Last edited: 22/08/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Nanne Frenkel
Scientific

Academic Medical Centre
Department of Vascular Medicine
Amsterdam
1105 AZ
Netherlands

Email	w.j.frenkel@amc.nl

Study information

Primary study design	Interventional
Study design	Non-randomised, controlled experimental study
Secondary study design	Non randomised controlled trial
Scientific title
Study objectives	Thiazide-induced hyponatraemia is caused by impaired free water excretion either due to alterations in the Arginine Dihydrolase (ADH) - Arginine Vasopressin Receptor 2 (AVPR2) - Aquaporin-2 (AQP2) pathway or impaired renal sodium handling.
Ethics approval(s)	Ethics approval received from the Medical Ethics Committee of the AMC on the 16th August 2007 (ref: MEC 07/059).
Health condition(s) or problem(s) studied	Thiazide induced hyponatraemia
Intervention	All subjects included in this controlled experiment will receive a single dose of Hydrochloorthiazide 50 mg. After that they will be monitored for 24 hours.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Hydrochloorthiazide
Primary outcome measure(s)	Effect of a single oral dose hydrochloorthiazide 50 mg intake on the serum and urine sodium, serum ADH, prostaglandin E2 and urinary aquaporin-2 excretion in elderly patients (aged 60 - 80 years) with previous thiazide-induced hyponatraemia (sodium less than 125 mmol/l) without another cause for their hyponatraemia and matched controls receiving a thiazide diuretic without hyponatraemia. Urinary hydrochlorothiazide concentrations are measured to analyse differences in thiazide metabolism. The response to ADH will be assessed by expression of AVPR2 in a cell-culture and determine its activity by measurement of cyclic Adenosine Monophospahte (cAMP). Outcomes will be measured at baseline (n = 0) and after 4, 8 and 24 hours.
Key secondary outcome measure(s)	To identify (elderly) patients who are at risk of thiazide induced hyponatraemia. Outcomes will be measured at baseline (n = 0) and after 4, 8 and 24 hours.
Completion date	01/08/2008

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Not Specified
Target sample size at registration	36
Key inclusion criteria	1. Age 60 - 80 years 2. Previously admitted with thiazide-induced hyponatraemia 3. Patients must be willing and medically able to discontinue anti-hypertensive therapy six weeks before the study and for the duration of the study 4. Patients must be willing to be admitted for 24 hours and must be medically able to take the study medication 5. Patients must be willing to give informed consent
Key exclusion criteria	1. Other causes for hyponatraemia (e.g. heart failure, pulmonary disease, medication associated with hyponatraemia) 2. Renal dysfunction (estimated clearance less than 50 ml/min according to Cockroft-Gault) 3. Liver cirrhosis 4. Heart failure 5. Medication: antipressiva (Selective Serotonin Reuptake Inhibitors [SSRIs]), antiepileptica, prednisone, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), opioids, other diuretics (e.g. lasix, burinex, chloorthalidon, dytac) 6. Allergy for sulphonamide derivates 7. Therapy resistant hypertension (Blood Pressure [BP] greater than 140/90 mmHg while using three or more anti-hypertensive drugs)
Date of first enrolment	01/08/2007
Date of final enrolment	01/08/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Centre

Amsterdam
1105 AZ
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan