High Water Intake in Polycystic Kidney Disease

Study Overview
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Brief Summary
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DRINK is an open-label randomised controlled feasibility trial of high versus ad libitum water intake in ADPKD.

Detailed Description
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Autosomal Dominant Polycystic Kidney Disease (PKD) affects 12.5 million people worldwide, and accounts for 7% of those requiring renal replacement therapy. The hormone vasopressin drives cyst growth until ultimately most of the normal functioning kidney tissue is replaced and compressed by cysts over the life course. Half of those affected will require dialysis by the age of 55 years. Vasopressin blockade has emerged as a viable strategy for altering disease course. High water intake suppresses vasopressin, and may therefore slow cyst growth and consequent disease progression. However, evidence to support high water intake in PKD is lacking, and it is not clear whether patients can adhere sufficiently to a high water intake. DRINK is a single-centre prospective, open label, parallel group randomised controlled feasibility trial. The primary objective is to establish whether a definitive large randomised trial comparing high versus ad libitum water intake on long-term disease progression is deliverable. Fifty patients will be recruited from the Renal Genetics service at Addenbrooke's Hospital. Participants will be randomly allocated to the high water intake (high) or the ad libitum (standard) water intake group. For the high intake group the aim is to drink large enough volumes of water to achieve and maintain dilute urine (urine osmolality < 270 mOsmo/kg or urine specific gravity ≤ 1.010 ). Multiple methods will be employed to promote adherence these include instruction and education as well as self-monitoring of urine specific gravity twice weekly by participants and the recording of results via a trial specific smartphone application.

Official Title
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Determining Feasibility of Randomisation to High vs ad Libitum Water Intake in Polycystic Kidney Disease: The DRINK Randomised Feasibility Trial

Conditions
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Autosomal Dominant Polycystic Kidney Disease

Intervention / Treatment
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* Dietary Supplement: High water intake
* Other: Ad libitum water intake


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have given written informed consent to participate Aged 16 years or older Have a diagnosis of ADPKD (fulfilling radiological diagnostic criteria ± genetic evidence) eGFR ≥ 20ml/min/1.73m2 Able to self-monitor urine SG Exclusion Criteria: Inability to provide informed consent eGFR < 20ml/min/1.73m2 Fluid overload states e.g. heart failure, cirrhosis, or requirement for fluid restriction Confounding illness impacting on renal disease e.g. concomitant diabetes or glomerulonephritis Treatment with diuretics for fluid overload (those on diuretics for hypertension may participate in the trial after a run-in period of 2 weeks) Treatment with Tolvaptan in the last 4 weeks Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ad libitum water intake<br>Ad libitum water intake, defined as intake guided by thirst to achieve a target urine osmolality > 300 mOsmo/kg | Other: Ad libitum water intake<br>* Water intake guided by thirst<br>|
| Active Comparator: High water intake<br>Personalised daily water intake prescription to achieve target urine osmolality < 270 mOsm/kg. | Dietary Supplement: High water intake<br>* High water intake aimed at achieving an urine osmolality < 270mOsmo/kg. Individualised prescription for each participant based on the free water clearance formula calculation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieving a urine osmolality < 270 mOsm/kg |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine osmolality | Achieved urine osmolality as a surrogate for vasopressin suppression | 8 weeks | 
| Proportion of participants that can self-monitor and report urine specific gravity reliably |  | 8 weeks | 
| Proportion of patients experiencing a serious adverse event |  | 12 weeks | 
| Acute change in estimated GFR | Evaluation of the change form baseline eGFR after 2 weeks | 4 weeks | 
| Health-Related Quality of Life (HRQoL) | Change from baseline HRQoL as estimated by EQ5D-5L | 12 weeks | 
| Recruitment rate |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autosomal Dominant Polycystic Kidney Disease, Polycystic Kidney Disease, ADPKD, Water, Vasopressin, Dietary