Adaptation of Thirst to a Single Administration of Tolvaptan (TOLVATHIRST)

• Status: Unknown status
• Trial end date: 2020-12-30
• Target enrollment: 0
• Participant gender: All

Summary

Tolvaptan is a new drug that specifically antagonizes the V2-receptor of antidiuretic hormone (ADH) and leads to water diuresis: During acute administration of tolvaptan, the main fear is to induce a too fast increase in plasma sodium concentration and in turn brain damageHowever, the tolvaptan-induced increase in plasma sodium concentration is expected to stimulate thirst, preventing major negative water balance.

The investigators hypothesize that tolvaptan-induced increase in plasma osmolality (and sodium concentration) is dependent of thirst adaptation that is influenced by physiological factors, namely age and sex. To address the effect of a single oral administration of tolvaptan at a dosage used during hyponatremia (15 mg) under free water access in healthy volunteers. Primary outcome will be the maximal change in serum sodium concentration within the 6 hours following tolvaptan administration.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Otsuka Pharmaceutical Europe Ltd
• Treatments: Tolvaptan

Criteria

Inclusion Criteria:

• To be 18-85 years old at the date of inclusion, both sex

• to have his/her full-legal capacity and understand the study protocol,

• to be covered by health insurance,

• to give his/her written informed consent

Exclusion Criteria:

• On-going pregnancy,

• women of childbearing age without efficient contraception,

• breastfeeding women,

• all acute (less than 7 days) pathological conditions,

• all active chronic diseases, especially those that could be interfering with water balance and/or thirst and/or renal response to tolvaptan,

• any prohibited treatment since at least 8 days (tolerated : calcium channel blockers, statins, acetaminophen, oral contraception and impregnated sterilets of progesterone are tolerated if necessary),

• hypersensitivity to tolvaptan or its excipients

• severe history of allergy (i.e. dyspnea, edema, cutaneous rash…) secondary to any drug administration

• participants with anuria orurinary pathway obstruction (complete or partial)

• natremia ≤133 mmol/l or ≥145 mmol/l

• hypovolemia

• SGOT, SGPT > 1.5 fold upper normal values

• estimated GFR (CKD epi) < 60 ml/min/1.73 m2,)

• current participation to (or being in exclusion period of) another interventional study.