Cardiovascular DiseasesPhase 2NCT01638663
Effect of the Aquaretic Tolvaptan on Nitric Oxide System (TORA)
A Phase 2 study testing Tolvaptan in people with Cardiovascular Diseases and Nephropathy, run by Regional Hospital Holstebro at 1 site in Denmark.
Trial summary
The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Nephropathy
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- May 2012to Mar 2014
- 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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women, age 18-40 years
- Body Mass Index (BMI) 18,5-30 kg/m2
Who cannot join
- Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
- Neoplastic disease
- Drug abuse
- Alcohol abuse
- Medical treatment except peroral anticontraceptive
- Pregnancy
Show all 11Show fewer
- Smoking
- Abnormal blood and urine sample
- Abnormal ECG
- Blood donation within a month before examination
- Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Vasopressin Antagonism on Renal Sodium and Water Handling and Circulation During Inhibition of the Nitric Oxide System in Healthy Subjects
The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects.
Read the detailed description
Tolvaptan is a vasopressin antagonist (V2-antagonist) and is used in treatment of hyponatremia. Animal studies have demonstrated that inhibition of V2 receptors in the renal principal cell increases renal free water clearance and renal sodium excretion.
Treatment with V2-receptor antagonists increases vasopressin concentration in plasma that stimulates V1-receptors in the vascular bed. This may change both central and peripheral hemodynamics and plasma concentration of vasoactive hormones. Changes in hemodynamics and hormone concentration may consequently change renal sodium and water handling.
The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure.
The effects of tolvaptan the circulation and kidneys is investigated by using measurements of biomarkers specific for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of tolvaptan and L-NMMA infusion.
- Conditions
- Cardiovascular Diseases, Nephropathy
- Being tested
- Tolvaptan, Placebo
- Keywords
- Tolvaptan, L-NMMA, Healthy subjects, Nephrology, Cardiology
- Medical subject headings
- Cardiovascular Diseases, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called Samsca
15 mg pr day for 1 day
PlaceboDrug
Also called Unikalk
1 tablet Unikalk 1 pr day for 1 day
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Active comparator | Oral administration of 15 mg Tolvaptan on each examination day. Receives: Drug: Tolvaptan |
| Placebo | Placebo comparator | Oral administration of 15 mg Unikalk tablet on each examination day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CH2O
Measurement of H2O clearance at baseline, during and after L-NMMA infusion.
Measured: 5-6 Hours
Secondary outcomes (6)
Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)
Measured: 5-6 Hours
Central blood pressure
Measured: 5-6 Hours
Pulse wave velocity
Measured: 5-6 Hours
Augmentation Index
Measured: 5-6 Hours
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Measured: 5-6 Hours
Fractional sodium excretion
Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
Measured: 5-6 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2012 (estimated)
- Study startMay 2012
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regional Hospital Holstebro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erling Bjerregaard Pedersen, Regional Hospital Holstebro
- Investigators
- Safa Therwani, Bachelor, Principal investigator, Medicinsk Forskning
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01638663
- Sponsor's protocol ID
- SAFA-1-2012
- Status last verified
- Oct 2014
- First submitted
- 6 Jul 2012
- Last updated
- 9 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vasopressin Antagonism on Renal Sodium and Water Handling and Circulation During Inhibition of the Nitric Oxide System in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01638663
- Acronym / sponsor ID
- SAFA-1-2012
- Conditions
- Cardiovascular Diseases, Nephropathy
- Keywords
- Tolvaptan, L-NMMA, Healthy subjects, Nephrology, Cardiology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Regional Hospital HolstebroUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 12 Jul 2012 (estimated)
- 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.
The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects.
Detailed description
Tolvaptan is a vasopressin antagonist (V2-antagonist) and is used in treatment of hyponatremia. Animal studies have demonstrated that inhibition of V2 receptors in the renal principal cell increases renal free water clearance and renal sodium excretion.
Treatment with V2-receptor antagonists increases vasopressin concentration in plasma that stimulates V1-receptors in the vascular bed. This may change both central and peripheral hemodynamics and plasma concentration of vasoactive hormones. Changes in hemodynamics and hormone concentration may consequently change renal sodium and water handling.
The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure.
The effects of tolvaptan the circulation and kidneys is investigated by using measurements of biomarkers specific for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of tolvaptan and L-NMMA infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Active comparator | Drug: TolvaptanOral administration of 15 mg Tolvaptan on each examination day. |
| Placebo | Placebo comparator | Drug: PlaceboOral administration of 15 mg Unikalk tablet on each examination day. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Men and women, age 18-40 years
- Body Mass Index (BMI) 18,5-30 kg/m2
Key exclusion criteria (11 listed)
- Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
- Neoplastic disease
- Drug abuse
- Alcohol abuse
- Medical treatment except peroral anticontraceptive
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 |
|---|---|---|
| TolvaptanAlso: Samsca15 mg pr day for 1 day | Drug | Tolvaptan |
| PlaceboAlso: Unikalk1 tablet Unikalk 1 pr day for 1 day | Drug | Placebo |
Primary outcome
CH2O
Time frame: 5-6 Hours
Measurement of H2O clearance at baseline, during and after L-NMMA infusion.
6 secondary outcomes
Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)
Time frame: 5-6 Hours
Central blood pressure
Time frame: 5-6 Hours
Pulse wave velocity
Time frame: 5-6 Hours
Augmentation Index
Time frame: 5-6 Hours
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Time frame: 5-6 Hours
Fractional sodium excretion
Time frame: 5-6 Hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2014.
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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.
Safa Therwani, Bachelor principal investigator
Medicinsk Forskning
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 in people with Cardiovascular Diseases and Nephropathy, run by Regional Hospital Holstebro at 1 site in Denmark.
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 2 inclusion and 11 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: finished, as of the sponsor's last update on 9 Oct 2014. 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 Denmark. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CH2O (time frame: 5-6 Hours). 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 9 Oct 2014.