Condition category
Urological and Genital Diseases
Date applied
09/01/2017
Date assigned
26/01/2017
Last edited
26/01/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Diabetes mellitus is a long-term condition where a person is unable to control their blood sugar levels. There are two main types of diabetes, type 1 (around 10% of cases) and type 2. In type 1 diabetes (T1DM) the immune system attacks specialised cells in the pancreas which are responsible for producing the hormone insulin (which is responsible for converting sugar in the blood to stored sugar). T1DM sufferers have a high risk of developing complications from their diabetes. Around 30-40% of diabetic patients develop kidney disease. Eventually, the kidneys are no longer able to support the body’s needs (kidney failure) and so a treatment to replace the work of the failed kidneys is needed, such as dialysis (where the blood is cleaned by a machine) or transplantation of a healthy kidney. As kidney disease progresses, a protein called albumin leaks into the urine (macroalbuminuria), which affects the kidney’s ability to filter the blood. Drug treatments that are now routinely used and proven to prevent kidney failure were first evaluated in patients with T1DM and macroalbuminuria. These drugs all demonstrated early reductions in macroalbuminuria which helped delay the onset of kidney failure. However these drugs do not work for everyone and so patients with T1DM and macroalbuminuria remain at high risk of kidney failure. Ursodeoxycholic acid is a chemical found in bile which is produced by the liver to help dissolve fats. It is currently approved for clinical use and treatment of gall stones and liver disease. In laboratory and animal studies Ursodeoxycholic acid reduces albuminuria and prevents the progression of kidney damage. The aim of this study is to find out whether treatment with Ursodeoxycholic acid can help protect the kidneys in T1DM patients with macroalbuminuria.

Who can participate?
T1DM patients aged between 20 and 75 who have macroalbuminuria.

What does the study involve?
Participants are randomly allocated to receive two treatments in a random order with a four week no-treatment period between the two treatments. The first treatment involves taking Ursodeoxycholic acid every day for 24 weeks and the second treatment involves taking a placebo (dummy drug) everyday for 24 weeks. At the start and end of each 24 week period, participants have a urine sample taken to measure the protein present and a blood sample to test their liver function. In addition they have an ECG test (heart rhythm monitoring test) to check their heart function.

What are the possible benefits and risks of participating?
There is no guarantee of any direct medical benefit from participating in this study. This study will be part of an effort to collect more information about a drug that may provide potential benefit to others in the future. Risks of participation in the study include potential side effects from the study drug itself, such as soft, loose stools and diarrhoea, rash, or hardening of gallstones due to build-up of calcium. There is a also a risk of pain or bruising from blood tests or skin irritation from electrodes (sticky conductive pads) used in heart rhythm monitoring.

Where is the study run from?
Diabetes Unit, Guy’s Hospital (UK)

When is the study starting and how long is it expected to run for?
June 2015 to January 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Chantelle Farr

Trial website

Contact information

Type

Public

Primary contact

Dr Chantelle Farr

ORCID ID

Contact details

Department of Diabetes and Endocrinology
3rd Floor - Southwark Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 20 7188 8472
chantelle.farr@gstt.nhs.uk

Additional identifiers

EudraCT number

2015-003609-41

ClinicalTrials.gov number

Protocol/serial number

31972

Study information

Scientific title

The renoprotective effects of Ursodeoxycholic acid in patients with type 1 diabetes and macroalbuminuria

Acronym

Study hypothesis

The aim of this study is to evaluate if Ursodeoxycholic acid reduces albuminuria in patients with type 1 diabetes mellitus (T1DM) with residual macroalbuminuria despite established standard care.

Ethics approval

London - Bloomsbury Research Ethics Committee, 19/04/2016, ref: 15/LO/1951

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Diabetes, Primary sub-specialty: Both; UKCRC code/ Disease: Renal and Urogenital/ Renal failure

Intervention

Participants are randomly allocated to receive two treatments in a random order, with a 4 week wash out period of no treatment between.

Treatment one: Participants receive Ursodeoxycholic acid (500mg bid) for 24 weeks.
Treatment two: Participants receive a placebo for 24 weeks.

The total duration of participation for both treatment arms lasts for approximately 54 weeks and includes 7 visits to the study centre at Guy’s Hospital London.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Albumin excretion rate (AER) is measured using a standard laboratory test on three non-consecutive timed overnight urine specimens collected one week prior to visit at baseline and 24 weeks for each treatment period.

Secondary outcome measures

1. Brachial blood pressure is measured using an automated sphygmomanometer at baseline and 24 weeks
2. Central aortic blood pressure and Ao-PWV are measured using applanation tonometry… at baseline and 24 weeks
3. Glycated haemoglobin (HbA1c) is measured using blood test at baseline and 24 weeks
4. Plasma albumin is measured using blood test at baseline and 24 weeks
5. Liver function is measured using blood test at baseline and 24 weeks
6. Urine electrolytes are measured using urine test at baseline and 24 weeks
7. Endothelial and renal markers are measured using blood tests and flow mediated dilation at baseline and 24 weeks

Overall trial start date

01/06/2015

Overall trial end date

01/01/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. T1DM patients aged 20 to 75 years, with residual macroalbuminuria
2. Estimated GFR ≥30 ml/min
3. Written informed consent to participate in the study prior to any study procedures
4. Ability to communicate and comply with all study procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant exclusion criteria

1. History of intolerance to Ursodeoxycholic acid
2. Active gastrointestinal disease (such as gall stones, inflammatory bowel disease, primary sclerosing cholangitis)
3. Non-diabetic renal disease
4. Absence of diabetic retinopathy
5. Pregnancy or lactation (female participants)
6. Insufficient understanding of the trial

Recruitment start date

12/01/2016

Recruitment end date

06/06/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy’s Hospital
Diabetes Unit Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

King’s College London and Guy’s and St Thomas’ NHS Foundation Trust

Sponsor details

King’s Health Partners Clinical Trial Office
16th Floor
Tower Wing
Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 20 7188 5732
jackie.pullen@kcl.ac.uk

Sponsor type

University/education

Website

Organisation

Guy’s and St Thomas’s NHS Foundation Trust

Sponsor details

16th Floor
Tower Wing
Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
+44 20 7188 7188 x51447
Jennifer.Boston@gstt.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/06/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes