Healthy VolunteersPhase 2TOLVATHIRSTNCT03931369
Adaptation of Thirst to a Single Administration of Tolvaptan (TOLVATHIRST)
A Phase 2 study testing Tolvaptan 15 MG in people with Healthy Volunteers, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Tolvaptan 15 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- 6 Sep 2019to 30 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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),
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Administration of TOLVAptan at a Dosage Used in the Treatment of Hyponatremia: Changes in THIRST and Water Balance in Healthy Volunteers
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.
Read the 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
- Being tested
- Tolvaptan 15 MG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolvaptan 15 MGDrug
Single administration of one pill of 15 MG tolvaptan
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan test | Experimental | 15 MG pill administered tolvatan once, one day Receives: Drug: Tolvaptan 15 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in serum sodium concentration
Measured: Baseline and 6 hours following tolvaptan administration
Secondary outcomes (7)
change in plasma osmolality
Measured: Baseline and 6 hours following tolvaptan administration
change urinary sodium excretion
Measured: Baseline and 6 hours following tolvaptan administration
change urinary potassium excretion
Measured: Baseline and 6 hours following tolvaptan administration
change urinary calcium excretion
Measured: Baseline and 6 hours following tolvaptan administration
change urinary magnesium excretion
Measured: Baseline and 6 hours following tolvaptan administration
change urinary Acide excretion
Measured: Baseline and 6 hours following tolvaptan administration
change urinary chloride excretion
Measured: Baseline and 6 hours following tolvaptan administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start6 Sep 2019 (estimated)
- Primary completion30 Dec 2020 (estimated)
- Study completion30 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka Pharmaceutical Europe Ltd
- Responsible party
- Sponsor
- Investigators
- Anne BLANCHARD, MD, PhD, Principal investigator, Assistance Publique des Hopitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03931369
- Sponsor's protocol ID
- APHP180494
- Other IDs
- 2019-001335-31, 2019
- Acronym
- TOLVATHIRST
- Status last verified
- Sep 2019
- First submitted
- 15 Apr 2019
- Last updated
- 10 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD underlying published results
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Administration of TOLVAptan at a Dosage Used in the Treatment of Hyponatremia: Changes in THIRST and Water Balance in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03931369
- Acronym / sponsor ID
- TOLVATHIRST / APHP180494
- Conditions
- Healthy Volunteers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Otsuka Pharmaceutical Europe Ltd
- Study start
- 6 Sep 2019 (estimated)
- Primary completion
- 30 Dec 2020 (estimated)
- Study completion
- 30 Dec 2020 (estimated)
- First posted
- 30 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan test | Experimental | Drug: Tolvaptan 15 MG15 MG pill administered tolvatan once, one day |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tolvaptan 15 MGSingle administration of one pill of 15 MG tolvaptan | Drug | Tolvaptan test |
Primary outcome
change in serum sodium concentration
Time frame: Baseline and 6 hours following tolvaptan administration
7 secondary outcomes
change in plasma osmolality
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary sodium excretion
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary potassium excretion
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary calcium excretion
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary magnesium excretion
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary Acide excretion
Time frame: Baseline and 6 hours following tolvaptan administration
change urinary chloride excretion
Time frame: Baseline and 6 hours following tolvaptan administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Individual participant dataSharing planned: Yes. IPD underlying published results
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Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne BLANCHARD, MD, PhD principal investigator
Assistance Publique des Hopitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tolvaptan 15 MG in people with Healthy Volunteers, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karine GOUDE-ORY (+33(0)1 44 84 17 22, karine.goude@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in serum sodium concentration (time frame: Baseline and 6 hours following tolvaptan administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.