Condition category
Urological and Genital Diseases
Date applied
02/11/2016
Date assigned
02/11/2016
Last edited
02/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Type 2 diabetes mellitus (T2DM) is a growing problem worldwide. People with T2DM have difficulty controlling their blood sugar (glucose) as they do not produce enough insulin to function properly (insulin deficiency), or that the body’s cells don’t react to insulin as they should do (insulin resistance). Type 2 Diabetes can lead to a range of complications, including damage to the kidneys. It is known that maintaining normal blood sugar levels with drugs helps to slow the progression of kidney disease in diabetic patients. Hypoglycaemia is a term used to describe blood sugar levels that are too low. Hypoglycaemia is not always recognised by patients and is more common in patients with kidney disease who have had diabetes for a long time. Gliclazide is currently the most commonly used diabetic drug in the UK for patients with Type 2 Diabetes with kidney disease. Over the last ten years, a new class of diabetic drugs called Gliptins (including the drug Linagliptin) have become available which have been shown to cause less hypoglycaemia than Gliclazide. The aim of this study is to find out whether treatment with Linagliptin is safer and leads to fewer episodes of hypoglycaemia than Gliclazide, in patients with Type 2 Diabetes and moderate to severe long-term kidney disease. In addition, the study aims to find out how often unrecognised hypoglycaemic episodes occur in patients on Linagliptin compared to Gliclazide, whether Linagliptin is better than Gliclazide at protecting the kidney by mechanisms independent of just lowering blood sugar levels, and which of the two drugs makes patients feel better in themselves.

Who can participate?
Adults aged between 50 and 75 years who have had T2DM for at least 10 years, have moderate to severe long-term kidney disease, and are currently being treated with Gliclazide.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group continue taking their Gliclazide and those in the second group start taking Linagliptin instead. At the start of the study, participants in both groups have a device called a continuous glucose monitor (CGM) put in place to continuously monitor their blood sugar levels. This involves having a small sensor inserted under the skin, which measures blood sugar levels every 5 minutes over two seven day periods at the start of the study and then after eight weeks. During the two 7-day periods, patients are also asked to complete a food diary and obtain fingerprick sugar measurements using a home glucometer four times per day.
Blood and urine samples are also collected at the start of the study and after eight weeks to measure biomarkers (natural indicators) that are associated with a decline in kidney function. Participants also complete a questionnaire to see how they are feeling.

What are the possible benefits and risks of participating?
Participants benefit from receiving their test results and explanations at the end of the study so they have more information about their diabetic control. There is a risk of minor bruising at the site where blood samples were taken, occasional minor bleeding and bruising when the CGM sensor is inserted under the skin, occasional irritation from the adhesive dressing used to secure the sensor to the skin, and occasional discomfort from the fitting and wearing of the CGM. Sometimes, the sensor may become dislodged and sound an alarm. Any changes to diabetic medication carries a small risk of affecting diabetic control, however, this will be closely monitored to minimise that risk.

Where is the study run from?
1. Hammersmith Hosptial (UK)
2. St Mary's Hospital (UK)

When is the study starting and how long is it expected to run for?
August 2014 to July 2018

How long will the trial be recruiting participants for?
Boehringer Ingelheim Ltd (UK)

Who is the main contact?
Mr Thomas Walters
thomas.walters@imperial.nhs.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Thomas Walters

ORCID ID

Contact details

Renal Research Office
2nd Floor Hammersmith House
Hammersmith Hospital
Imperial College Healthcare NHS Trust
Du Cane Road
London
W12 0HS
United Kingdom
+44 203 313 7309
thomas.walters@nihr.ac.uk

Additional identifiers

EudraCT number

2015-002309-12

ClinicalTrials.gov number

Protocol/serial number

30706

Study information

Scientific title

A randomised controlled trial of the sulfonylurea Gliclazide and the DPP-4 inhibitor Linagliptin On the frequency of hypOglyCaemia amOng patients with Type 2 DiabeteS and chronic kidnEy disease (CKD) stage 3b and 4

Acronym

GLOOCOSE

Study hypothesis

1. Linagliptin is associated with fewer episodes of hypoglycaemia than Gliclazide in patients with Type 2 Diabetes and moderate to severe kidney disease
2. Linagliptin reduces biochemical markers in the blood and urine associated with deteriorating kidney function and kidney disease progression
3. Patients feel better when they are taking Linagliptin, compared to Gliclazide

Ethics approval

London Brent Research Ethics Committee, 30112015, ref: 15/LO/1548

Study design

Single-centre open-label unblinded randomised controlled Phase IV trial

Primary study design

Interventional

Secondary study design

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

Intervention

Participants will undergo automated computer randomisation (using the InForm study database) to either continuing with their current treatment and dose of oral Gliclazide, or switching to oral Linagliptin 5 mg daily for eight weeks. If they were also taking Metformin, then they will continue on this. Prior to randomisation, study participants will be fitted with a continuous glucose monitor (CGM) which will capture and record interstitial glucose readings for seven days, and allow assessment of overall glycaemic control. They will also be taught to perform capillary glucose readings using a home glucose monitor (to allow CGM calibration), and complete food diaries over the week.

Eight weeks after randomisation, they will repeat this process for another 7-day period. Blood and urine samples will be obtained from study participants before and after randomisation for analysis of renal function, full blood count, HbA1c for glycaemic control, urinary albumin excretion and renal biomarkers MCP-1 and TGF-beta 1. Study patients will also be required to complete the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline and 8 weeks post-randomisation.

Intervention type

Drug

Phase

Phase IV

Drug names

1. Linagliptin
2. Gliclazide

Primary outcome measures

Overall glycaemic control and percent of time spent in hypoglycaemia will be assessed using data captured on the Medtronic iPro2 Continuous Glucose Monitor over a two 7 day periods (a minimum of continuous 48 hours of CGM monitoring) and home capillary blood glucose monitoring at Visit 1 (baseline, before randomisation) and Visit 4 (7 weeks after randomisation).

Secondary outcome measures

1. Serum and Urinary markers of inflammation and fibrosis will be analysed by measuring urinary albumin excretion and serum and urinary MCP-1 and TGF-beta 1 at Visit 2 (randomisation visit, 1 week after baseline visit) and Visit 5 (final study visit, 8 weeks after randomisation)
2. Treatment satisfaction will be measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at Visit 2 (randomisation visit, 1 week after baseline visit) and Visit 5 (final study visit, 8 weeks after randomisation)

Overall trial start date

12/08/2014

Overall trial end date

31/07/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Type 2 Diabetes of 10 years or more duration
2. Age between 50 years and 75 years
3. eGFR 15 to 45 ml/min/1.73m2
4. HbA1c < 65 mmol/mol (< 8%)
5. Taking Gliclazide (with or without Metformin)
6. Stable diabetic control for the last 2 months prior to randomisation
7. Individuals who understand adequate written and verbal English

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

1. Type 1 Diabetes
2. Currently on insulin, pioglitazone, other dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists
3. Immunosuppressive therapy (excluding inhaled steroids) within the previous 6 months
4. Pregnant or lactating women
5. Malignancy or other life threatening illness
6. Inability to give informed consent

Recruitment start date

17/06/2016

Recruitment end date

16/06/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Hammersmith Hospital
Imperial College Healthcare NHS Trust Renal Research Office 2nd Floor Hammersmith House Du Cane Road
London
W12 0HS
United Kingdom

Trial participating centre

St Mary's Hospital
Imperial College Healthcare NHS Trust Imperial Clinical Respiratory Research Unit (ICRRU) 1st Floor, Mint Wing Praed Street
London
W2 1NY
United Kingdom

Sponsor information

Organisation

Imperial College London

Sponsor details

AHSC Joint Research Compliance Office
Imperial College London and Imperial College Healthcare NHS Trust
Room 215
Level 2
Medical School Building
St Mary's Hospital
Norfolk Place
London
W2 1PG
United Kingdom

Sponsor type

Research organisation

Website

http://www.imperial.ac.uk/joint-research-compliance-office/

Funders

Funder type

Industry

Funder name

Boehringer Ingelheim Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

All publications and presentations relating to the study will be authorised by the Trial Management Group. Planned submission of an abstract and have an oral presentation in June/July 2018 and submission the full paper in October 2018. Both participants and their registered GPs will be sent a letter regarding the outcome of the study, and the funder will be notified of the trial results.

IPD Sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from Thomas.Walters@imperial.nhs.uk

Intention to publish date

31/03/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

02/03/2017: Verified study information with principal investigator.