High Water Intake in Polycystic Kidney Disease (DRINK)

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

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

Study Overview

• Status: Completed
• Conditions: Autosomal Dominant Polycystic Kidney Disease
• Intervention / Treatment: Other: Ad libitum water intake; Dietary supplement: High water intake

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: Addenbrookes Charitable Trust; PKD Charity; British Renal Society & British Kidney Patient Association
• Investigators: Principal Investigator: Thomas F Himestra, Cambridge University Hospital NHS Foundation Trust

Publications and helpful links

General Publications

• El-Damanawi R, Lee M, Harris T, Mader LB, Bond S, Pavey H, Sandford RN, Wilkinson IB, Burrows A, Woznowski P, Ben-Shlomo Y, Karet Frankl FE, Hiemstra TF. Randomised controlled trial of high versus ad libitum water intake in patients with autosomal dominant polycystic kidney disease: rationale and design of the DRINK feasibility trial. BMJ Open. 2018 May 9;8(5):e022859. doi: 10.1136/bmjopen-2018-022859.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2016
• Primary Completion (Actual): March 31, 2018
• Study Completion (Actual): July 31, 2018

Study Registration Dates

• First Submitted: September 18, 2016
• First Submitted That Met QC Criteria: October 12, 2016
• First Posted (Estimate): October 14, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 13, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: ADPKD; Vasopressin; Autosomal Dominant Polycystic Kidney Disease; Water; Polycystic Kidney Disease; Dietary
• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
• Other Study ID Numbers: 203565

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES