Condition category
Genetic Diseases
Date applied
02/11/2016
Date assigned
23/11/2016
Last edited
16/10/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition where the sufferer develops many cysts (fluid filled sacs) in their kidneys. These cysts are non-cancerous, but over the years they grow in size and number causing health problems. By the age of 30-50 years most people with the condition will have high blood pressure and long-term kidney disease. Half of those affected will have kidney failure that needs either dialysis or a kidney transplant by the age of 60 years. It is common, affecting approximately 1 in every 800 people in the United Kingdom. Vasopressin is a hormone produced by the brain. Its role is to maintain the body’s water balance. In states of dehydration it acts on the kidneys to conserve water and produce concentrated urine. If the body is well hydrated, the body stops making vasopressin and dilute urine is produced. Research has shown that in polycystic kidney disease, the vasopressin hormone acts in an abnormal way. It drives the cysts to grow, so there are many more cysts and causes more fluid to collect inside them so they grow even bigger. Therefore, stopping vasopressin production through high water intake could slow the progression of ADPKD.

Who can participate?
Patients with ADPKD aged 16 years and over.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are given a personalised daily water prescription (usually between 2-4 litres), to produce dilute enough urine to stop vasopressin being made by the body for eight weeks. Those in the second group are asked to continue to drink as they normally would for eight weeks. Participants in both groups attend appointments five times over the course of the eight week study and then four weeks afterwards. At these visits, participants have a medical and dietary review, blood and urine tests, and are asked to complete a questionnaire.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved with participating in this study.

Where is the study run from?
Addenbrookes Hosital (UK)

When is the study starting and how long is it expected to run for?
February 2016 to April 2018

Who is funding the study?
British Renal Society (UK)

Who is the main contact?
Dr Ragada El-Damanawi
ragmed11@doctors.org.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ragada El-Damanawi

ORCID ID

Contact details

Cambridge Clinical Trials Unit
Level 6 Coton House
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 596 471
ragmed11@doctors.org.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

31605

Study information

Scientific title

Determining feasibility of Randomisation to high vs. ad libitum water Intake in Polycystic Kidney Disease: the DRINK randomised feasibility trial

Acronym

DRINK

Study hypothesis

The aim of this study is to determine whether giving participants a daily prescription for water intake, aimed at achieving dilute urine at a threshold that will stop vasopressin production by the body, is safe, sustainable and well tolerated by participants.

Ethics approval

Research Ethics Committee East of England, 11/07/2016, ref: 16/EE/0236

Study design

Randomised; Interventional; Design type: Treatment, Prevention, Education or Self-Management, Dietary, Active Monitoring

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Renal disorders, Primary sub-specialty: Renal disorders; UKCRC code/ Disease: Renal and Urogenital/ Other disorders of kidney and ureter

Intervention

Participants will be randomly assigned (1:1) to one of two groups.

Prescribed water intake (Group HW): Each participant has an individualised daily water prescription based on the free water clearance formula. They will be monitored throughout and if they are not achieving urine osmolality <270mosom/kg the water prescription will be adjusted further.

Ad libitum water intake (Group AW): Participants will be allowed to drink water as guided by thirst, patients who consume large quantities will be encouraged to reduce excessive water intake in a supervised manner aiming for a urine osmolality > 300mosom/kg.

Participants in both groups will have five face-to-face visits, with an additional end of trial visit at 12 weeks. During each visit they will undergo interview, targeted physical examination (fluid assessment, vital signs and weight), routine biochemistry and urine tests for osmolality and specific gravity (SG). They will be required to provide 24-hour urine collections at the screening visit, week 2 and week 8. This will guide adjustments to water prescription in the intervention group, and provide some information about the degree of correlation of measured urine osmolality with urine SG.

Participants will be taught how to measure their own urine SG by stick testing. They will receive an SMS text twice weekly prompting them to measure their urine SG and input the result into the smartphone application, this will help guide their fluid prescription further and ensure they are meeting their urine dilution targets.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Proportion of patients achieving a urine osmolality < 270 mOsm/kg is measured using 24 hour urine collections at screening, weeks 2, 8 and 12.

Secondary outcome measures

1. Urine osmolality is measured using 24 hour urine collections at screening, weeks 2, 8 and 12
2. Proportion of participants that can self-monitor and report urine specific gravity reliably is measured using home monitoring of urine dipstick testing twice weekly (Monday and thursday) from weeks 0-8
3. Proportion of patients experiencing a serious adverse event is measured using participant reported symptoms, clinic visits, and blood tests at weeks 0, 2, 4, 8 and 12
4. Estimated GFR is measured using blood test at screening, then weeks 0, 2, 4, 8 and 12
5. Health-Related Quality of Life is measured using the EQ5D-5L questionnaire at week 0 then week 12
6. Recruitment rate is measured using the number of participants recruited each month

Overall trial start date

01/02/2016

Overall trial end date

01/04/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Have given written informed consent to participate
2. Aged 16 years or older
3. Have a diagnosis of ADPKD (fulfilling radiological diagnostic criteria ± genetic evidence)
4. eGFR ≥ 20ml/min/1.73m2
5. Able to self-monitor urine SG

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

1. Inability to provide informed consent
2. eGFR < 20ml/min
3. Fluid overload states e.g. heart failure, cirrhosis, or requirement for fluid restriction
4. Confounding illness impacting on renal disease e.g. concomitant diabetes or glomerulonephritis
5. Treatment with diuretics for fluid overload (those on diuretics for hypertension may participate in the trial after a run-in period of 2 weeks)
6. Treatment with Tolvaptan in the last 4 weeks
7. Pregnancy or breastfeeding

Recruitment start date

27/09/2016

Recruitment end date

01/01/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrookes Hosital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust and University of Cambridge

Sponsor details

Research & Development Department (Box 277)
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 245 151
r&denquiries@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

British Renal Society

Alternative name(s)

BRS

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned peer review in a high impact peer reviewed journal. Results will also be disseminated via the trial website.

IPD Sharing plan:
The datasets generated during and/or analysed during the current study will be stored in a publically available repository [Cambridge Data Repository - http://www.data.cam.ac.uk/repository]

Intention to publish date

01/08/2018

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/10/2017: The following changes were made to the trial record: 1. The recruitment end date was changed from 27/03/2017 to 01/01/2018. 2. The overall trial end date was changed from 27/09/2017 to 01/04/2018. 3. The intention to publish date was changed from 01/03/2018 to 01/08/2018.