NephropathyPhase 2DOVANCT02078973
Effect of the Aquaretic Tolvaptan on Nitric Oxide System. A Dose-response Study (DOVA)
A Phase 2 study testing 15 mg tolvaptan, 30 mg tolvaptan and 45 mg tolvaptan in people with Nephropathy, run by Regional Hospital Holstebro at 1 site in Denmark.
Trial summary
Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Nephropathy
- What is being tested?
- 15 mg tolvaptan, 30 mg tolvaptan and 45 mg tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Mar 2014to Jan 2016
- 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: The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.
Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.
The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).
- Conditions
- Nephropathy
- Being tested
- 15 mg tolvaptan, 30 mg tolvaptan, 45 mg tolvaptan, Placebo
- Keywords
- Tolvaptan, L-NMMA, Healthy subjects, Nephrology
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
15 mg tolvaptanDrug
Also called Samsca
15 mg pr day for 1 day
30 mg tolvaptanDrug
Also called Samsca
30 mg pr day for 1 day
45 mg tolvaptanDrug
Also called Samsca
45 mg pr day for 1 day
PlaceboDrug
Also called Unikalk
1 tablet Unikalk pr day for 1 day
| Study group | Role | What they receive |
|---|---|---|
| 15 mg tolvaptan | Active comparator | Oral administration of 15 mg tolvaptan on each examination day. Receives: Drug: 15 mg tolvaptan |
| 30 mg tolvaptan | Active comparator | Oral administration of 30 mg tolvaptan on each examination day. Receives: Drug: 30 mg tolvaptan |
| 45 mg tolvaptan | Active comparator | Oral administration of 45 mg tolvaptan on each examination day. Receives: Drug: 45 mg tolvaptan |
| Placebo | Placebo comparator | Oral administration of a Unikalk tablet 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 (5)
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Measured: 5-6 Hours
Central and brachial blood pressure
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 posted5 Mar 2014 (estimated)
- Study start1 Mar 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NephropathyStudies 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regional Hospital Holstebro
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital
- Responsible party
- Principal investigator, Erling Bjerregaard Pedersen, Regional Hospital Holstebro
- Investigators
- Frank H Mose, MD, PhD, Principal investigator, Department of medical research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078973
- Sponsor's protocol ID
- SAFA-1-2014
- Other IDs
- 2013-003800-38
- Acronym
- DOVA
- Status last verified
- Feb 2017
- First submitted
- 1 Mar 2014
- Last updated
- 1 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Al Therwani S, Rosenbaek JB, Mose FH, Bech JN, Pedersen EB. Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects. BMC Nephrol. 2017 Mar 13;18(1):86. doi: 10.1186/s12882-017-0501-1.
PubMed 28288570
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.
- ClinicalTrials.gov ID
- NCT02078973
- Acronym / sponsor ID
- DOVA / SAFA-1-2014
- Conditions
- Nephropathy
- Keywords
- Tolvaptan, L-NMMA, Healthy subjects, Nephrology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Regional Hospital HolstebroUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- 1 Mar 2014 (actual)
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 5 Mar 2014 (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.
Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.
The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 15 mg tolvaptan | Active comparator | Drug: 15 mg tolvaptanOral administration of 15 mg tolvaptan on each examination day. |
| 30 mg tolvaptan | Active comparator | Drug: 30 mg tolvaptanOral administration of 30 mg tolvaptan on each examination day. |
| 45 mg tolvaptan | Active comparator | Drug: 45 mg tolvaptanOral administration of 45 mg tolvaptan on each examination day. |
| Placebo | Placebo comparator | Drug: PlaceboOral administration of a Unikalk tablet |
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 |
|---|---|---|
| 15 mg tolvaptanAlso: Samsca15 mg pr day for 1 day | Drug | 15 mg tolvaptan |
| 30 mg tolvaptanAlso: Samsca30 mg pr day for 1 day | Drug | 30 mg tolvaptan |
| 45 mg tolvaptanAlso: Samsca45 mg pr day for 1 day | Drug | 45 mg tolvaptan |
| PlaceboAlso: Unikalk1 tablet Unikalk 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
5 secondary outcomes
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Time frame: 5-6 Hours
Central and brachial blood pressure
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 1 Mar 2017.
- Derived from this study: PubMed 28288570Al Therwani S, Rosenbaek JB, Mose FH, Bech JN, Pedersen EB. Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects. BMC Nephrol. 2017 Mar 13;18(1):86. doi: 10.1186/s12882-017-0501-1.
Related trials for Nephropathy
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Population Pharmacokinetics of Temocillin in Acute Enterobacterial Pyelonephritis in Children
Pyelonephritis
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
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.
Frank H Mose, MD, PhD principal investigator
Department of medical research
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 15 mg tolvaptan, 30 mg tolvaptan and 45 mg tolvaptan in people with 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 1 Mar 2017. 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?
On the ClinicalTrials.gov record for NCT02078973, which also lists 1 linked publication.
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 1 Mar 2017.