High Water Intake in Polycystic Kidney Disease (DRINK)

• ClinicalTrials.gov Identifier: NCT02933268
• Recruitment Status: Completed
• First Posted: October 14, 2016
• Last Update Posted: January 15, 2019
• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: PKD Charity; Addenbrookes Charitable Trust; British Renal Society & British Kidney Patient Association
• Information provided by (Responsible Party): Dr Thomas Hiemstra, University of Cambridge

Tracking Information

• First Submitted Date: September 18, 2016
• First Posted Date: October 14, 2016
• Last Update Posted Date: January 15, 2019
• Actual Study Start Date: September 26, 2016
• Actual Primary Completion Date: March 31, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 12, 2016): The proportion of patients achieving a urine osmolality < 270 mOsm/kg [ Time Frame: 8 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2016)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High Water Intake in Polycystic Kidney Disease
• Official Title: Determining Feasibility of Randomisation to High vs ad Libitum Water Intake in Polycystic Kidney Disease: The DRINK Randomised Feasibility Trial
• Brief Summary: DRINK is an open-label randomised controlled feasibility trial of high versus ad libitum water intake in ADPKD.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Autosomal Dominant Polycystic Kidney Disease

Intervention

• 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.
• Other: Ad libitum water intake
  Water intake guided by thirst

Study Arms

• 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
  Intervention: Other: Ad libitum water intake
• Active Comparator: High water intake
  Personalised daily water intake prescription to achieve target urine osmolality < 270 mOsm/kg.
  Intervention: Dietary Supplement: High water intake

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 13, 2019): 42
• Original Estimated Enrollment (submitted: October 12, 2016): 50
• Actual Study Completion Date: July 31, 2018
• Actual Primary Completion Date: March 31, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02933268
• Other Study ID Numbers: 203565
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Dr Thomas Hiemstra, University of Cambridge
• Study Sponsor: Cambridge University Hospitals NHS Foundation Trust

Collaborators

• PKD Charity
• Addenbrookes Charitable Trust
• British Renal Society & British Kidney Patient Association

Investigators

• Principal Investigator: Thomas F Himestra; Cambridge University Hospital NHS Foundation Trust

• PRS Account: Cambridge University Hospitals NHS Foundation Trust
• Verification Date: January 2019