PolyuriaDIATNCT03858439
Dietary Intervention in ADPKD on Tolvaptan
A study testing Dietary in people with Polyuria and Autosomal Dominant Polycystic Kidney, run by McMaster University at 1 site in Canada.
Trial summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Tolvaptan has been approved in Canada as a treatment for ADPKD. Tolvaptan is an arginine vasopressin receptor antagonist which has been shown to decrease the progression of ADPKD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polyuria, Autosomal Dominant Polycystic Kidney
- What is being tested?
- Dietary
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- 6 Jun 2019to 16 May 2022
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients seen in the Hamilton Nephrology Genetics Clinic with a diagnosis of ADPKD taking tolvaptan
- Able to provide informed consent
- On maximal tolerated dose of tolvaptan for at least 3 months
Who cannot join
- Serum sodium > 135 mmol/L
- Patients with evidence of non-compliance (not completing monthly blood work required while on tolvaptan therapy).
- Unlikely to continue in Hamilton Nephrology Genetics Clinic for at least 6 months (planned dialysis initiation, transplant)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dietary Intervention in Patients With ADPKD on Tolvaptan: Urine Output and Quality of Life
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Tolvaptan has been approved in Canada as a treatment for ADPKD. Tolvaptan is an arginine vasopressin receptor antagonist which has been shown to decrease the progression of ADPKD. The main side effect of this treatment is increased urine output which leads to cessation of therapy in about 20% of patients. Low solute (low sodium, low protein) diet may alleviate this side effect. This is a single arm before / after study of dietary intervention on urine output and quality of life in ADPKD patients on a stable dose of tolvaptan.
Read the detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder affecting 12.5 million persons worldwide, and impacting approximately 35,000-66,000 Canadians. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years.
Tolvaptan has been approved in Canada as a treatment for ADPKD. Tolvaptan was discovered in Japan by Otsuka Pharmaceutical and was first approved there for ADPKD in 2014. The Health Canada approval of Tolvaptan is based on the results of the pivotal Phase 3 randomized, double-blind and placebo-controlled TEMPO 3:4 Trial, the largest study conducted to date in adults with ADPKD.
The treatment of ADPKD had previously been symptomatic with the aim of reducing morbidity and mortality associated with disease manifestations. This changed with the publication of the TEMPO 3:4 trial, which proved the efficacy of the arginine vasopressin (AVP) V2 receptor antagonist tolvaptan in decreasing the progression of CKD. In this trial, 1445 patients with ADPKD eGFR > 60 were randomized to receive either placebo or tolvaptan in a split-dose regimen of 45 mg in the morning and 15 mg in the afternoon, up titrated to 90/30 mg as tolerated. The REPRISE study investigated the value of tolvaptan in 1300 patients with lower levels of eGFR (25-65 mL/min/1.73 m2).
AVP plays a major role in the pathogenesis of cysts in ADPKD via cAMP stimulation. The AVP antagonist blocks V2 receptors in collecting ducts and therefore blocks the concentrating ability of the tubule. This leads to increased urine volume. Recently, it has been demonstrated that this increased urine volume is related to solute excretion. Therefore, it seems possible that dietary modification to decrease solute intake (salt, protein) would decrease the urine volume in patients taking tolvaptan.
The most common side effect of AVP antagonist is increased renal water excretion which presents as polyuria, nocturia, increased thirst, and dry mouth. The daily urine volumes 5 days after starting different split doses of tolvaptan (15/15, 30/0, 30/15, 30/30 mg) in a preliminary phase 2 study were 4 to 6 L. In the treatment of hyponatremia and heart failure (another indication for tolvaptan therapy), a meta-analysis found an average increase in water clearance of only 68 mL/h after tolvaptan treatment. This more modest increase in urine output may be related to the low sodium diet most of these patients should be adhering to.
- Conditions
- Polyuria, Autosomal Dominant Polycystic Kidney
- Being tested
- Dietary
- Medical subject headings
- Polyuria, Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DietaryOther
Low sodium, low protein dietary recommendation
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Single arm study. All participants will receive dietary intervention. Receives: Other: Dietary |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 24-hour urine volume
24-hour urine volume in ml.
Measured: Change from baseline to 3 months
Secondary outcomes (3)
Change in ADPKD-IS
Autosomal dominant polycystic kidney disease impact score - quality of life. Eighteen items, score from 18 to 90 with higher values reflecting lower quality of life
Measured: Change from baseline to 3 months
Change in Nagasaki Diabetes Insipidus Questionnaire
Validated measure of polyuria on quality of life. Subset of questions 1-10 will be used (Questions 11-12 relate to therapy with DDAVP). Score from 10 to 40 with higher scores reflecting worse quality of life.
Measured: Change from baseline to 3 months
Change in urine total solute
Urine total solute measured by (urine sodium + urine urea) * urine volume
Measured: Change from baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2019
- Study start6 Jun 2019
- Primary completion24 Sep 2021
- Study completion16 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PolyuriaStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group before / after dietary intervention.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Margetts, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03858439
- Sponsor's protocol ID
- v1
- Acronym
- DIAT
- Status last verified
- Mar 2024
- First submitted
- 4 Feb 2019
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Intervention in Patients With ADPKD on Tolvaptan: Urine Output and Quality of Life
- ClinicalTrials.gov ID
- NCT03858439
- Acronym / sponsor ID
- DIAT / v1
- Conditions
- Polyuria, Autosomal Dominant Polycystic Kidney
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 6 Jun 2019 (actual)
- Primary completion
- 24 Sep 2021 (actual)
- Study completion
- 16 May 2022 (actual)
- First posted
- 28 Feb 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.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Tolvaptan has been approved in Canada as a treatment for ADPKD. Tolvaptan is an arginine vasopressin receptor antagonist which has been shown to decrease the progression of ADPKD. The main side effect of this treatment is increased urine output which leads to cessation of therapy in about 20% of patients. Low solute (low sodium, low protein) diet may alleviate this side effect. This is a single arm before / after study of dietary intervention on urine output and quality of life in ADPKD patients on a stable dose of tolvaptan.
Detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder affecting 12.5 million persons worldwide, and impacting approximately 35,000-66,000 Canadians. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years.
Tolvaptan has been approved in Canada as a treatment for ADPKD. Tolvaptan was discovered in Japan by Otsuka Pharmaceutical and was first approved there for ADPKD in 2014. The Health Canada approval of Tolvaptan is based on the results of the pivotal Phase 3 randomized, double-blind and placebo-controlled TEMPO 3:4 Trial, the largest study conducted to date in adults with ADPKD.
The treatment of ADPKD had previously been symptomatic with the aim of reducing morbidity and mortality associated with disease manifestations. This changed with the publication of the TEMPO 3:4 trial, which proved the efficacy of the arginine vasopressin (AVP) V2 receptor antagonist tolvaptan in decreasing the progression of CKD. In this trial, 1445 patients with ADPKD eGFR > 60 were randomized to receive either placebo or tolvaptan in a split-dose regimen of 45 mg in the morning and 15 mg in the afternoon, up titrated to 90/30 mg as tolerated. The REPRISE study investigated the value of tolvaptan in 1300 patients with lower levels of eGFR (25-65 mL/min/1.73 m2).
AVP plays a major role in the pathogenesis of cysts in ADPKD via cAMP stimulation. The AVP antagonist blocks V2 receptors in collecting ducts and therefore blocks the concentrating ability of the tubule. This leads to increased urine volume. Recently, it has been demonstrated that this increased urine volume is related to solute excretion. Therefore, it seems possible that dietary modification to decrease solute intake (salt, protein) would decrease the urine volume in patients taking tolvaptan.
The most common side effect of AVP antagonist is increased renal water excretion which presents as polyuria, nocturia, increased thirst, and dry mouth. The daily urine volumes 5 days after starting different split doses of tolvaptan (15/15, 30/0, 30/15, 30/30 mg) in a preliminary phase 2 study were 4 to 6 L. In the treatment of hyponatremia and heart failure (another indication for tolvaptan therapy), a meta-analysis found an average increase in water clearance of only 68 mL/h after tolvaptan treatment. This more modest increase in urine output may be related to the low sodium diet most of these patients should be adhering to.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group before / after dietary intervention.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: DietarySingle arm study. All participants will receive dietary intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients seen in the Hamilton Nephrology Genetics Clinic with a diagnosis of ADPKD taking tolvaptan
- Able to provide informed consent
- On maximal tolerated dose of tolvaptan for at least 3 months
Key exclusion criteria (3 listed)
- Serum sodium > 135 mmol/L
- Patients with evidence of non-compliance (not completing monthly blood work required while on tolvaptan therapy).
- Unlikely to continue in Hamilton Nephrology Genetics Clinic for at least 6 months (planned dialysis initiation, transplant)
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 |
|---|---|---|
| DietaryLow sodium, low protein dietary recommendation | Other | Intervention |
Primary outcome
Change in 24-hour urine volume
Time frame: Change from baseline to 3 months
24-hour urine volume in ml.
3 secondary outcomes
Change in ADPKD-IS
Time frame: Change from baseline to 3 months
Change in Nagasaki Diabetes Insipidus Questionnaire
Time frame: Change from baseline to 3 months
Change in urine total solute
Time frame: Change from baseline to 3 months
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 15 Mar 2024.
- Individual participant dataSharing planned: No
Related trials for Polyuria
RecruitingPhase 3
HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
ADPKD
Recruiting
Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome
Arginine Vasopressin Deficiency, Primary Polydipsia
RecruitingObservational study
Secretin in Refeeding
Anorexia in Adolescence
RecruitingPhase 4
A Clinical Observation Study of a Chinese Patent Medicine Combined With Tamsulosin in Improving Sleep and Nocturia Symptoms After Enucleation of the Prostate
Benign Prostatic Hyperplasia, Nocturia Associated With Nocturnal Polyuria
RecruitingObservational study
Lymphoedema and Nocturia/Nocturnal Polyuria After Pelvic LND for Urogenital Cancer
Urogenital Cancer, Lower Limb Lymphedema
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary in people with Polyuria and Autosomal Dominant Polycystic Kidney, run by McMaster University at 1 site in Canada.
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 3 inclusion and 3 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 15 Mar 2024. 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 Canada. 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.
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?
Change in 24-hour urine volume (time frame: Change from baseline to 3 months). 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 15 Mar 2024.