Dietary Intervention in ADPKD on Tolvaptan (DIAT)
Primary Purpose
Polyuria, Autosomal Dominant Polycystic Kidney
Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Dietary
Sponsored by
About this trial
This is an interventional treatment trial for Polyuria
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- St. Joseph's HealthcareRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intervention
Arm Description
Single arm study. All participants will receive dietary intervention.
Outcomes
Primary Outcome Measures
Change in 24-hour urine volume
24-hour urine volume in ml.
Secondary Outcome Measures
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
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.
Change in urine total solute
Urine total solute measured by (urine sodium + urine urea) * urine volume
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03858439
Brief Title
Dietary Intervention in ADPKD on Tolvaptan
Acronym
DIAT
Official Title
Dietary Intervention in Patients With ADPKD on Tolvaptan: Urine Output and Quality of Life
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 6, 2019 (Actual)
Primary Completion Date
September 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polyuria, Autosomal Dominant Polycystic Kidney
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single group before / after dietary intervention.
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Experimental
Arm Description
Single arm study. All participants will receive dietary intervention.
Intervention Type
Other
Intervention Name(s)
Dietary
Intervention Description
Low sodium, low protein dietary recommendation
Primary Outcome Measure Information:
Title
Change in 24-hour urine volume
Description
24-hour urine volume in ml.
Time Frame
Change from baseline to 3 months
Secondary Outcome Measure Information:
Title
Change in ADPKD-IS
Description
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
Time Frame
Change from baseline to 3 months
Title
Change in Nagasaki Diabetes Insipidus Questionnaire
Description
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.
Time Frame
Change from baseline to 3 months
Title
Change in urine total solute
Description
Urine total solute measured by (urine sodium + urine urea) * urine volume
Time Frame
Change from baseline to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Margetts, MD PhD
Phone
9055221155
Ext
32299
Email
margetts@mcmaster.ca
Facility Information:
Facility Name
St. Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Margetts, MD PhD
Phone
9055221155
Ext
32299
Email
margetts@mcmaster.ca
First Name & Middle Initial & Last Name & Degree
Matt Lanktree, MD PhD
Phone
9055221155
Ext
33323
Email
mblanktree@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Dietary Intervention in ADPKD on Tolvaptan
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