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Dietary Intervention in ADPKD on Tolvaptan (DIAT)

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ClinicalTrials.gov Identifier: NCT03858439
Recruitment Status : Recruiting
First Posted : February 28, 2019
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
Peter Margetts, McMaster University

Tracking Information
First Submitted Date  ICMJE February 4, 2019
First Posted Date  ICMJE February 28, 2019
Last Update Posted Date March 5, 2020
Actual Study Start Date  ICMJE June 6, 2019
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
Change in 24-hour urine volume [ Time Frame: Change from baseline to 3 months ]
24-hour urine volume in ml.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
  • Change in ADPKD-IS [ Time Frame: Change from baseline to 3 months ]
    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 [ Time Frame: Change from baseline to 3 months ]
    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 [ Time Frame: Change from baseline to 3 months ]
    Urine total solute measured by (urine sodium + urine urea) * urine volume
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dietary Intervention in ADPKD on Tolvaptan
Official Title  ICMJE Dietary Intervention in Patients With ADPKD on Tolvaptan: Urine Output and Quality of Life
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single group before / after dietary intervention.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Polyuria
  • Autosomal Dominant Polycystic Kidney
Intervention  ICMJE Other: Dietary
Low sodium, low protein dietary recommendation
Study Arms  ICMJE Experimental: Intervention
Single arm study. All participants will receive dietary intervention.
Intervention: Other: Dietary
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 27, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients seen in the Hamilton Nephrology Genetics Clinic with a diagnosis of ADPKD taking tolvaptan
  2. Able to provide informed consent
  3. On maximal tolerated dose of tolvaptan for at least 3 months

Exclusion Criteria:

  1. Serum sodium > 135 mmol/L
  2. Patients with evidence of non-compliance (not completing monthly blood work required while on tolvaptan therapy).
  3. Unlikely to continue in Hamilton Nephrology Genetics Clinic for at least 6 months (planned dialysis initiation, transplant)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peter Margetts, MD PhD 9055221155 ext 32299 margetts@mcmaster.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03858439
Other Study ID Numbers  ICMJE v1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Peter Margetts, McMaster University
Study Sponsor  ICMJE McMaster University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account McMaster University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP