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

NCT ID: NCT03931369

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-06
• Study Completion Date: 2020-12-30

Brief 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.

Detailed Description

Tolvaptan is a new drug that specifically antagonizes the V2-receptor of antidiuretic hormone (ADH) and leads to water diuresis: its beneficial effects have been demonstrated for hyponatremia due to a syndrome of inappropriate antidiuresis (SIAD). During acute administration of tolvaptan, the main fear is to induce a too fast increase in plasma sodium concentration and in turn brain damage. An acute increase in serum sodium concentration has been observed in water restricted subjects. However, the tolvaptan-induced increase in plasma sodium concentration is expected to stimulate thirst, preventing major negative water balance. In non-water restricted subjects, this has never been studied. Moreover, this physiological adaptation may change according to age and gender. The investigatorshypothesize that healthy volunteers will adapt normally to an acute tolvaptan administration, thirst helping to maintain plasma sodium and osmolality within the normal range. The final tolvaptan-induced increase in plasma osmolality will depend on thirst adaptation, influenced by physiological factors, namely age and sex.

Sixty subjects (30 male, 30 female) from 18 to 85 years old will be recruited from the database of healthy subjects of the Clinical Investigation Center of the European Georges Pompidou Hospital, Paris, France. They will have two visits: one inclusion safety visit without administration, and 2 to 15 days later, an experimental visit. During the later visit water and electrolyte output and water intake will be monitored hourly two hours before and six hours after single administration of 15 mg tolvaptan.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Tolvaptan test

15 MG pill administered tolvatan once, one day

Group Type: EXPERIMENTAL

Tolvaptan 15 MG

Intervention Type: DRUG

Single administration of one pill of 15 MG tolvaptan

Interventions

Tolvaptan 15 MG

Single administration of one pill of 15 MG tolvaptan

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Otsuka Pharmaceutical Europe Ltd

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne BLANCHARD, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique des Hopitaux de Paris

Locations

AP-HP Hôpital Européen Georges Pompidou

Paris, , France

Countries

France

Central Contacts

Karine GOUDE-ORY

Role: CONTACT

karine.goude@aphp.fr

+33(0)1 44 84 17 22

Hakima MANSEUR

Role: CONTACT

hakima.manseur@aphp.fr

+33(0)1 56 09 59 71

Other Identifiers

2019-001335-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP180494

Identifier Type: -

Identifier Source: org_study_id