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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
  1. Ragada El-Damanawi1,2,
  2. Michael Lee3,
  3. Tess Harris4,
  4. Laura B Mader2,5,
  5. Simon Bond2,
  6. Holly Pavey2,
  7. Richard N Sandford6,
  8. Ian B Wilkinson1,2,
  9. Alison Burrows7,
  10. Przemyslaw Woznowski7,
  11. Yoav Ben-Shlomo7,
  12. Fiona E Karet Frankl6,
  13. Thomas F Hiemstra1,2
  1. 1 Division of Experimental Medicine and Immunotherapeutics, Department of Medicine, University of Cambridge, Cambridge, UK
  2. 2 Cambridge Clinical Trials Unit, Cambridge, UK
  3. 3 Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
  4. 4 PKD Charity, London, UK
  5. 5 Patient Led Research Hub, Cambridge, UK
  6. 6 Department of Medical Genetics, University of Cambridge, Cambridge, UK
  7. 7 University of Bristol, Bristol, UK
  1. Correspondence to Dr Thomas F Hiemstra; tfh24{at}cam.ac.uk

Abstract

Introduction Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) leading to enlarged kidneys, hypertension and renal failure. Vasopressin receptor blockade slows disease progression. Physiological suppression of vasopressin secretion through high water (HW) intake could achieve a similar effect, necessitating a definitive large-scale trial of HW intake in ADPKD. The objective of the DRINK trial is to answer the key design and feasibility questions required to deliver a successful definitive water intake trial.

Methods and analysis We describe the design of a single-centre, open-label, prospective, randomised controlled trial. The "Determining feasibility of R andomisation to high vs. ad libitum water In take in Polycystic K idney Disease" (DRINK) trial aims to enrol 50 patients with ADPKD, over the age of 16 years with an estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2. Participants will be randomised 1:1 to HW intake based on an individualised water intake prescription, or to ad libitum (AW) water intake. The HW group will aim for a dilute urine (urine osmolality ≤270 mOsm/kg) as a surrogate marker of vasopressin suppression, and those in the AW group will target more concentrated urine. Participants will have an 8-week treatment period, and will be seen at weeks 0, 2, 4 and 8, undergoing assessments of fluid status, renal function and serum and urine osmolalities. They will receive dietary advice, and self-monitor urine specific gravity and fluid intake. The trial employs smartphone technology to permit home monitoring and remote direct data capture. The primary feasibility end points are recruitment rate and separation between arms in measured urinary osmolality. Key secondary assessments include acceptability, adherence, health-related quality of life, acute effects of HW intake on measured (51Cr-EDTA) and eGFR and ADPKD-related pain.

Ethics and dissemination Ethical approval was awarded by the East of England Essex Research Ethics Committee (16/EE/0026). The results of DRINK will be submitted to peer-reviewed journals, and presented to patients via the PKD Charity.

Trial registration number NCT02933268 and ISCRTN16794957

  • autosomal dominant polcystic kidney disease
  • vasopressin
  • water
  • osmolality
  • urine specific gravity
  • feasibility

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Footnotes

  • Contributors All the authors contributed to the design and development of the study protocol, and have reviewed the manuscript. TFH and TH conceived the study. TFH, RE-D, IBW, FEKF and RNS designed the study, and contributed to recruitment, trial oversight and implementation of the intervention. ML provided specific support with regard to the assessment of pain in trial participants. SB and HP provided statistical expertise and supported the development of the statistical analysis plan. LBM supported the development of the patient-led proposal through the Patient Led Research Hub. AB, PW and YB-S developed the SPLASH app and contributed to development of the protocol for the SPLASH substudy.

  • Funding The study is funded by the British Renal Society and Kidney Care UK (formerly British Kidney Patient Association) grant programme (15-004), the PKD Charity, the Addenbrooke’s Charitable Trust (45/16) and Kidney Research UK (TF-009-20161125), and is supported by the UKCRC-registered Cambridge Clinical Trials Unit and the Cambridge NIHR Clinical Research Facility.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval East of England Essex Research Ethics Committee (16/EE/0026).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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