HealthyPhase 1NCT03910231
The Role of Vasopressin Antagonism on Renal Sodium Handling
A Phase 1 study testing Tolvaptan Oral Tablet in people with Healthy, run by Brigham and Women's Hospital.
Trial summary
Vasopressin has primarily been considered to be a water and osmosis regulating hormone that mediates its effects on renal aquaporin channels. Recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Tolvaptan Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2012to 1 Feb 2015
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- - Blood pressure <130/85 mmHg and >100/50 mmHg
- Normal laboratory values for (see "Normal Values" table):
- Complete blood count
- Serum creatinine, sodium, potassium, glucose, liver enzymes
- Urinalysis
- ECG
Who cannot join
- - Alcohol intake >12 oz per week
- Tobacco or recreational drug use
- History of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months
- Any prescription medication or herbal medication use except oral contraceptive or multivitamin
- Pregnancy or current breastfeeding
- First degree relative with hypertension, diabetes, stroke, renal or cardiac disease
About this study
Vasopressin has primarily been considered to be a water and osmosis regulating hormone that mediates its effects on renal aquaporin channels. Recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. The purpose of this human physiology study was to test whether antagonism of the V2R alters urine sodium excretion in normal healthy volunteers.
Read the detailed description
Vasopressin's potential roles in maintaining normal volume homeostasis are expanding. While previous data support the concept that vasopressin's primary role is in mediating water homeostasis, recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. This effect occurs via activation of the epithelial sodium channel (ENaC). These studies document that vasopressin via activation of the V2 receptor, not only reduces free water excretion but also sodium excretion. These data suggest that blocking this receptor under the right circumstances and in the right population may be effective in modulating hypertension in humans: specifically a V2 receptor antagonist may be effective in treating some individuals that have salt-sensitive hypertension. The current proposal will test in normal human subjects the proof of principle of the above stated hypothesis, and to assess the best markers to determine such an effect. It is important to perform studies with strict environmental control in a clinical research center because of the variability of environmental factors that can create confusion in interpreting data (dietary sodium, activity, body posture, diurnal variation, ambient temperature, sleep-wake cycle, etc.).
The overall program objective is to determine if a vasopressin V2 antagonist will be an effective treatment for salt-sensitive hypertension and if so, what subtype. The object of this specific proposal is to determine the effect of a selective V2 antagonist on sodium handling in normal subjects.
- Conditions
- Healthy
- Being tested
- Tolvaptan Oral Tablet
- Keywords
- vasopressin receptor, renal sodium excretion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolvaptan Oral TabletDrug
Tolvaptan, to block V2R
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: Tolvaptan Oral Tablet |
| 15mg Tolvaptan | Experimental | 15mg Tolvaptan Receives: Drug: Tolvaptan Oral Tablet |
| 30mg Tolvaptan | Experimental | 30mg Tolvaptan Receives: Drug: Tolvaptan Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute intravenous saline response
Urine sodium excretion measured in response to saline infusion
Measured: 6 hours
Secondary outcomes (1)
Dietary salt response
Cumulative sodium excretion measured in response to dietary salt loading
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2019
- Study start1 Feb 2012
- Primary completion30 Sep 2014
- Study completion1 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, placebo-controlled, double-blinded, parallel arm clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Jonathan S. Williams, MD, MMSc, Brigham and Women's Hospital
- Investigators
- Jonathan S Williams, MD, MMSc, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03910231
- Sponsor's protocol ID
- 2012P000638
- Status last verified
- Apr 2019
- First submitted
- 9 Apr 2019
- Last updated
- 10 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Stockand JD. Vasopressin regulation of renal sodium excretion. Kidney Int. 2010 Nov;78(9):849-56. doi: 10.1038/ki.2010.276. Epub 2010 Aug 25.
PubMed 20736986Bankir L, Bichet DG, Bouby N. Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension? Am J Physiol Renal Physiol. 2010 Nov;299(5):F917-28. doi: 10.1152/ajprenal.00413.2010. Epub 2010 Sep 8.
PubMed 20826569Blanchard A, Frank M, Wuerzner G, Peyrard S, Bankir L, Jeunemaitre X, Azizi M. Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent. Clin J Am Soc Nephrol. 2011 Apr;6(4):753-9. doi: 10.2215/CJN.06540810. Epub 2011 Jan 13.
PubMed 21233458Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003 Jun 3;107(21):2690-6. doi: 10.1161/01.CIR.0000070422.41439.04. Epub 2003 May 12.
PubMed 12742979Hauptman PJ, Zimmer C, Udelson J, Shoaf SE, Mallikaarjun S, Bramer SL, Orlandi C. Comparison of two doses and dosing regimens of tolvaptan in congestive heart failure. J Cardiovasc Pharmacol. 2005 Nov;46(5):609-14. doi: 10.1097/01.fjc.0000180899.24865.b6.
PubMed 16220067
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Vasopressin Antagonism on Renal Sodium Handling
- ClinicalTrials.gov ID
- NCT03910231
- Acronym / sponsor ID
- 2012P000638
- Conditions
- Healthy
- Keywords
- vasopressin receptor, renal sodium excretion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd.
- Study start
- 1 Feb 2012 (actual)
- Primary completion
- 30 Sep 2014 (actual)
- Study completion
- 1 Feb 2015 (actual)
- First posted
- 10 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.
Vasopressin has primarily been considered to be a water and osmosis regulating hormone that mediates its effects on renal aquaporin channels. Recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. The purpose of this human physiology study was to test whether antagonism of the V2R alters urine sodium excretion in normal healthy volunteers.
Detailed description
Vasopressin's potential roles in maintaining normal volume homeostasis are expanding. While previous data support the concept that vasopressin's primary role is in mediating water homeostasis, recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. This effect occurs via activation of the epithelial sodium channel (ENaC). These studies document that vasopressin via activation of the V2 receptor, not only reduces free water excretion but also sodium excretion. These data suggest that blocking this receptor under the right circumstances and in the right population may be effective in modulating hypertension in humans: specifically a V2 receptor antagonist may be effective in treating some individuals that have salt-sensitive hypertension. The current proposal will test in normal human subjects the proof of principle of the above stated hypothesis, and to assess the best markers to determine such an effect. It is important to perform studies with strict environmental control in a clinical research center because of the variability of environmental factors that can create confusion in interpreting data (dietary sodium, activity, body posture, diurnal variation, ambient temperature, sleep-wake cycle, etc.).
The overall program objective is to determine if a vasopressin V2 antagonist will be an effective treatment for salt-sensitive hypertension and if so, what subtype. The object of this specific proposal is to determine the effect of a selective V2 antagonist on sodium handling in normal subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Randomized, placebo-controlled, double-blinded, parallel arm clinical trial
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Tolvaptan Oral TabletPlacebo |
| 15mg Tolvaptan | Experimental | Drug: Tolvaptan Oral Tablet15mg Tolvaptan |
| 30mg Tolvaptan | Experimental | Drug: Tolvaptan Oral Tablet30mg Tolvaptan |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- - Blood pressure <130/85 mmHg and >100/50 mmHg
- Normal laboratory values for (see "Normal Values" table):
- Complete blood count
- Serum creatinine, sodium, potassium, glucose, liver enzymes
- Urinalysis
Key exclusion criteria (6 listed)
- - Alcohol intake >12 oz per week
- Tobacco or recreational drug use
- History of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months
- Any prescription medication or herbal medication use except oral contraceptive or multivitamin
- Pregnancy or current breastfeeding
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 Oral TabletTolvaptan, to block V2R | Drug | 15mg Tolvaptan, 30mg Tolvaptan, Placebo |
Primary outcome
Acute intravenous saline response
Time frame: 6 hours
Urine sodium excretion measured in response to saline infusion
1 secondary outcome
Dietary salt response
Time frame: 6 days
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 10 Apr 2019.
- Background: PubMed 20736986Stockand JD. Vasopressin regulation of renal sodium excretion. Kidney Int. 2010 Nov;78(9):849-56. doi: 10.1038/ki.2010.276. Epub 2010 Aug 25.
- Background: PubMed 20826569Bankir L, Bichet DG, Bouby N. Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension? Am J Physiol Renal Physiol. 2010 Nov;299(5):F917-28. doi: 10.1152/ajprenal.00413.2010. Epub 2010 Sep 8.
- Background: PubMed 21233458Blanchard A, Frank M, Wuerzner G, Peyrard S, Bankir L, Jeunemaitre X, Azizi M. Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent. Clin J Am Soc Nephrol. 2011 Apr;6(4):753-9. doi: 10.2215/CJN.06540810. Epub 2011 Jan 13.
- Background: PubMed 12742979Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003 Jun 3;107(21):2690-6. doi: 10.1161/01.CIR.0000070422.41439.04. Epub 2003 May 12.
- Background: PubMed 16220067Hauptman PJ, Zimmer C, Udelson J, Shoaf SE, Mallikaarjun S, Bramer SL, Orlandi C. Comparison of two doses and dosing regimens of tolvaptan in congestive heart failure. J Cardiovasc Pharmacol. 2005 Nov;46(5):609-14. doi: 10.1097/01.fjc.0000180899.24865.b6.
- Individual participant dataSharing planned: Yes
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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.
Jonathan S Williams, MD, MMSc principal investigator
Brigham and Women's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tolvaptan Oral Tablet in people with Healthy, run by Brigham and Women's Hospital.
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 6 inclusion and 6 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 10 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Acute intravenous saline response (time frame: 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 NCT03910231, which also lists 5 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 10 Apr 2019.