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Dietary Intervention in ADPKD on Tolvaptan (DIAT)

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

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.

Condition or disease Intervention/treatment Phase
Polyuria Autosomal Dominant Polycystic Kidney Other: Dietary Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single group before / after dietary intervention.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dietary Intervention in Patients With ADPKD on Tolvaptan: Urine Output and Quality of Life
Actual Study Start Date : June 6, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Intervention
Single arm study. All participants will receive dietary intervention.
Other: Dietary
Low sodium, low protein dietary recommendation

Primary Outcome Measures :
  1. Change in 24-hour urine volume [ Time Frame: Change from baseline to 3 months ]
    24-hour urine volume in ml.

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. Change in urine total solute [ Time Frame: Change from baseline to 3 months ]
    Urine total solute measured by (urine sodium + urine urea) * urine volume

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858439

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Contact: Peter Margetts, MD PhD 9055221155 ext 32299 margetts@mcmaster.ca

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Canada, Ontario
St. Joseph's Healthcare Recruiting
Hamilton, Ontario, Canada, L8N 4A6
Contact: Peter Margetts, MD PhD    9055221155 ext 32299    margetts@mcmaster.ca   
Contact: Matt Lanktree, MD PhD    9055221155 ext 33323    mblanktree@gmail.com   
Sponsors and Collaborators
McMaster University
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Responsible Party: Peter Margetts, Professor, McMaster University
ClinicalTrials.gov Identifier: NCT03858439    
Other Study ID Numbers: v1
First Posted: February 28, 2019    Key Record Dates
Last Update Posted: March 5, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Kidney Diseases, Cystic
Kidney Diseases
Urologic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Urination Disorders
Urological Manifestations