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

NCT03931369 | Unknown Phase 2 DMC

• 2 other identifiers: APHP1804942019-001335-31
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• change in serum sodium concentration

  Baseline and 6 hours following tolvaptan administration

Secondary Outcomes (7)

• change in plasma osmolality

  Baseline and 6 hours following tolvaptan administration

• change urinary sodium excretion

  Baseline and 6 hours following tolvaptan administration

• change urinary potassium excretion

  Baseline and 6 hours following tolvaptan administration

• change urinary calcium excretion

  Baseline and 6 hours following tolvaptan administration

• change urinary magnesium excretion

  Baseline and 6 hours following tolvaptan administration

Study Arms (1)

Tolvaptan test

EXPERIMENTAL

15 MG pill administered tolvatan once, one day

Drug: Tolvaptan 15 MG

Interventions

Tolvaptan 15 MG DRUG

Single administration of one pill of 15 MG tolvaptan

Tolvaptan test

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Otsuka Pharmaceutical Europe Ltd: collaborator

Study Sites (1)

AP-HP Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

MeSH Terms

Interventions

Tolvaptan

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anne BLANCHARD, MD, PhD

  Assistance Publique des Hopitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karine GOUDE-ORY

CONTACT

+33(0)1 44 84 17 22; karine.goude@aphp.fr

Hakima MANSEUR

CONTACT

+33(0)1 56 09 59 71; hakima.manseur@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 30, 2019
• Study Start: September 6, 2019
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: One year after the last publication
• Access Criteria: Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team. Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.

Locations

FR (1)