Autosomal Dominant Polycystic Kidney DiseasePhase 2TOPONCT02527863
Effect of the Aquaretic Tolvaptan on Nitric Oxide System
A Phase 2 study testing Tolvaptan in people with Autosomal Dominant Polycystic Kidney Disease, 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 65 years
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease
- 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
- 18 participants
- Where
- 1 siteDenmark
- Study dates
- Feb 2015to Aug 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Caucasian men and women
- Age between 18-65 years
- ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:
- patients with negative family history for ADKPD and more than 10 cysts in each kidney and no extrarenal or renal findings that suggest causes to cyst formation.
- patients with positive family history for ADPKD:
- 15-39 yr of age and at least 3 or more unilateral or bilateral.
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- 40-59 yr of age and 2 or more cysts in each kidney.
- 60 yr of age and at least 4 cysts in each kidney.
- Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),
- BMI between 18.5 and 35.5 kg/m2.
Who cannot join
- Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
- clinically significant abnormalities in blood or urine sample at the inclusion
- previous cerebrovascular insults,
- previous clinical evidence for aneurysm
- Alcohol or drug abuse,
- smoking,
Show all 10Show fewer
- pregnancy or breastfeeding,
- clinically significant changes in the electrocardiogram,
- medication except antihypertensive agents and oral contraceptives,
- blood pressure>170/105 mmHg despite treatment with metoprolol and/or amlodipine.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Medical Research and Medicine, Holstebro Regional Hospital
Holstebro, Holstebro, 7500
About this study
Official title: The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Central Hemodynamics During Baseline Conditions and After Inhibition of the Nitric Oxide System in Patients With Autosomal Dominant Polycystic Kidney Disease
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) in patients with autosomal dominant polycystic kidney disease.
- Being tested
- Tolvaptan, Placebo
- Keywords
- Tolvaptan, L-NMMA, ADPKD
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called Samsca
60 mg Tolvaptan pr day for 1 day
PlaceboDrug
Also called Unikalk
1 tablet Unikalk pr day for 1 day
| Study group | Role | What they receive |
|---|---|---|
| 60 mg Tolvaptan | Active comparator | Oral administration of 60 mg tolvaptan on each examination day. Receives: Drug: 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)
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 posted19 Aug 2015 (estimated)
- Study startFeb 2015
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies 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
- 18 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
- Erling B Pedersen, Study chair, Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527863
- Sponsor's protocol ID
- SAFA-2-2014
- Other IDs
- 2014-001973-15, 2014
- Acronym
- TOPO
- Status last verified
- Feb 2017
- First submitted
- 18 Feb 2015
- Last updated
- 1 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039Al Therwani S, Malmberg MES, Rosenbaek JB, Bech JN, Pedersen EB. Effect of tolvaptan on renal handling of water and sodium, GFR and central hemodynamics in autosomal dominant polycystic kidney disease during inhibition of the nitric oxide system: a randomized, placebo-controlled, double blind, crossover study. BMC Nephrol. 2017 Aug 15;18(1):268. doi: 10.1186/s12882-017-0686-3.
PubMed 28810844
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 Central Hemodynamics During Baseline Conditions and After Inhibition of the Nitric Oxide System in Patients With Autosomal Dominant Polycystic Kidney Disease
- ClinicalTrials.gov ID
- NCT02527863
- Acronym / sponsor ID
- TOPO / SAFA-2-2014
- Keywords
- Tolvaptan, L-NMMA, ADPKD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Regional Hospital HolstebroUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- Feb 2015 (actual)
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 19 Aug 2015 (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) in patients with autosomal dominant polycystic kidney disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 60 mg Tolvaptan | Active comparator | Drug: TolvaptanOral administration of 60 mg tolvaptan on each examination day. |
| Placebo | Placebo comparator | Drug: PlaceboOral administration of a Unikalk tablet. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Caucasian men and women
- Age between 18-65 years
- ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:
- Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),
- BMI between 18.5 and 35.5 kg/m2.
Key exclusion criteria (10 listed)
- Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
- clinically significant abnormalities in blood or urine sample at the inclusion
- previous cerebrovascular insults,
- previous clinical evidence for aneurysm
- Alcohol or drug abuse,
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: Samsca60 mg Tolvaptan pr day for 1 day | Drug | 60 mg Tolvaptan |
| PlaceboAlso: Unikalk1 tablet Unikalk pr day for 1 day | Drug | Placebo |
Primary outcome
CH2O (Measurement of H2O clearance)
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 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 28810844Al Therwani S, Malmberg MES, Rosenbaek JB, Bech JN, Pedersen EB. Effect of tolvaptan on renal handling of water and sodium, GFR and central hemodynamics in autosomal dominant polycystic kidney disease during inhibition of the nitric oxide system: a randomized, placebo-controlled, double blind, crossover study. BMC Nephrol. 2017 Aug 15;18(1):268. doi: 10.1186/s12882-017-0686-3.
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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.
Erling B Pedersen study chair
Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500
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 Autosomal Dominant Polycystic Kidney Disease, 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 10 inclusion and 10 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 (Measurement of H2O clearance) (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 NCT02527863, which also lists 2 linked publications.
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.