ISRCTN - ISRCTN00290196: The effect of lixisenatide in type 1 diabetes

Plain English Summary

Background and study aims
Lixisenatide has been developed as an drug for diabetes and has been shown to improve blood sugar control in people with type 2 diabetes. This study aims to find out whether a daily injection of lixisenatide, along with prescribed insulin treatment, can improve blood sugar control in people with type 1 diabetes. The study will also find out if there is a difference between participants who have low insulin production from the pancreas and those who do not have insulin production from the pancreas. Part A of this study aims to find out a safe dose of insulin when given with lixisenatide, so that the participants do not experience a higher than normal frequency of low blood sugar events. The Part B is aiming to see whether there is an effect on blood sugar levels, especially after meals, when a daily injection of lixisenatide is added to a participants usual insulin treatment.

Who can participate?
People aged 18-70 years who have had type 1 diabetes for at least 12 months and use insulin injections to control their disease can take part.

What does the study involve?
The Part A study will last about 8 days for each participant and will involve a maximum of 7 Churchill Hospital visits and 5 telephone calls from our research team. Each participant will receive lixisenatide daily for up to 4 days alongside their usual insulin medication. The Part B study will last about 16 weeks for each participant and will involve a maximum of 13 Churchill hospital visits and 6 telephone calls from our research team. There will be two different treatment periods each lasting for 4 weeks with an additional 4 weeks in between when each participant will take insulin alone (the washout period). Participants will receive lixisenatide for 4 weeks and a matching dummy or placebo drug for the other 4 weeks. Neither the study team nor the participants will know which is which.

What are the possible benefits and risks of participating?
There are no direct benefits to the participant for taking part in this exploratory study. However, the results may help researchers find the correct dose for the meal-time insulin when used with lixisenatide for the next part of the study. This study may lead to future large-scale studies and lixisenatide may become an additional treatment for patients with type 1 diabetes. Reported side effects of lixisenatide include nausea and vomiting, loss of appetite and weight loss. Most side effects settle within days of starting the medication. When lixisenatide is used with insulin there may be a small risk of low blood sugar. The participants insulin dose will be reduced while they take the study drug to minimise this risk. The dose used in the daily injection is the same as used in type 2 diabetes. The participants health will be monitored closely during the study and the study medication would be stopped should there be any cause for concern.

Where is the study run from?
Churchill Hospital, Oxford, UK.

When is the study starting and how long is it expected to run for?
May 2014 to June 2016

Who is funding the study?
Sanofi Aventis (UK).

Who is the main contact?
Dr Chitrabhanu Ballav (Principal Investigator)

Trial website

Contact information

Type

Scientific

Primary contact

Ms Irene Kennedy

ORCID ID

Contact details

Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
+44 1865 857255
irene.kennedy@dtu.ox.ac.uk

Additional identifiers

EudraCT number

2013-002259-14

ClinicalTrials.gov number

Protocol/serial number

15724

Study information

Scientific title

The effect of lixisenatide in type 1 diabetes: a randomised controlled trial

Acronym

LIXI

Study hypothesis

The study will take place in two parts (Parts A and B): The principal question of the Part A trial is to assess the amount of mealtime (prandial) insulin dose reduction that will avoid hypoglycaemic episodes (low blood sugar levels) when taken alongside a GLP1 receptor agonist called lixisenatide at a dose of 10 μg/day. The principal question of the Part B trial is to determine whether adding lixisenatide to basal bolus insulin (combination of long-acting insulin once a day, called basal, with short-acting insulin with meals, called bolus) significantly improves glycaemic (blood sugar) control during the 3-hour post-prandial period (i.e., following a meal) compared to basal bolus insulin and a 'dummy' or placebo injection.

Ethics approval

13/LO/1656; First MREC approval date 10/01/2014

Study design

Randomised; Interventional; Design type: Treatment

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

Topic: Diabetes; Subtopic: Type 1 ; Disease: Diabetic Control

Intervention

Part A study is open-label, without randomisation. All participants will receive 10 micrograms lixisentatide for up to 4 days and be followed up for 28 days after the last dose of the lixisenatide. Part B is a double-blinded trial. Two four-week treatment regimens will be applied in randomised order to participants as follows:
1. Lixisenatide 10 micrograms for 2 weeks
2. Lixisenatide 20 micrograms for 2 weeks
3. Washout period of 4 weeks
4. Matching placebo 10 micrograms for 2 weeks
5. Matching placebo 20 micrograms for 2 weeks
Neither the participant nor the trial team will know the treatment order. The participant will be followed up for 28 days after their last dose of lixisenatide (or matching placebo)

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measure

Lixisenatide effect on 3 hr post-prandial Continuous Glucose Monitoring readings compared to placebo; Timepoint(s): Part B trial.

Secondary outcome measures

HbA1c, insulin dose and glucagon change after standard mixed meal and insulin-induced hypoglycaemia; Timepoint(s): Following 4 weeks' compliance with study medication.

Overall trial start date

02/05/2014

Overall trial end date

30/06/2016

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Inclusion criteria as of 08/02/2016:
1. Has provided written informed consent
2. Type 1 diabetes
3. Diabetes duration for at least 12 months
4. Age 18-70 years inclusive (upper age limit specified for clinical safety as there is limited experience of using lixisenatide beyond 75 years
5. Basal-Bolus insulin regimen
6. HbA1c between 7.0% and 10.0% (inclusive)
7. Stable insulin dose (within 20%) over 3 months prior to recruitment. Patients on low doses of insulin who have had a change of insulin dose by >20% over the preceding 3 months may be included at the discretion of the Principal Investigator
8. BMI < 35 kg/m2
9. For the C-peptide positive group: random or fasting C-peptide = 0.1 nmol/l. If clinically indicated, screen negative for mutations in HNF1A, HNF4A or GCK genes (indicative of MODY, maturity onset diabetes of the young). For the C-peptide negative group: random or fasting C-peptide <0.01 nmol/l with accompanying glucose >4 mmol/l

Original inclusion criteria:
1. Has provided written informed consent
2. Type 1 diabetes
3. Diabetes duration for at least 12 months
4. Insulin treatment since the diagnosis of diabetes
5. Age 18-65 years (upper age limit specified for clinical safety as there is limited experience of using lixisenatide beyond 65 years)
6. Basal-Bolus insulin regimen
7. HbA1c between 7.0% and 9.0% (inclusive)
8. Stable insulin dose (within 20%) over 3 months prior to recruitment. Patients on low doses of insulin who have had a change of insulin dose by >20% over the preceding 3 months may be included at the discretion of the Principal Investigator
9. BMI < 30 kg/m2
10. For the C-peptide positive group: random or fasting C-peptide = 0.1 nmol/l. If clinically indicated, screen negative for mutations in HNF1A, HNF4A or GCK genes (indicative of MODY, maturity onset diabetes of the young). For the C-peptide negative group: random or fasting C-peptide <0.02 nmol/l with accompanying glucose >4 mmol/l

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 33; UK Sample Size: 33; Description: All participants will be patients with type 1 diabetes. There will be no controls in this trial.

Total final enrolment

27

Participant exclusion criteria

1. Type 2 diabetes
2. Maturity Onset Diabetes of the Young (MODY)
3. Pregnancy or women of childbearing age without adequate contraception
4. Women who are breastfeeding
5. Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
6. Renal impairment (eGFR ≤ 50 ml/min)
7. Abnormal liver function tests (> 1.5 x upper limit of the normal range)
8. Have high blood pressure (>180 mmHg systolic or >100 mmHgdiastolic)
9. Known ischaemic heart disease or heart failure
10. History of stroke
11. Patient has received any investigational drug within 30 days prior to screening
12. Oral steroid treatment 30 days prior to randomisation
13. Known malignancy or any other condition or circumstance, which, in the opinion of the investigator, would affect the patients ability to participate in the protocol
14. Non-English speakers will be excluded due to the nature and complexity of the hypoglycaemic clamp methodology
15. Known allergy to the drugs or any of the components
16. Severe hypoglycaemia requiring third party intervention on more than one occasion in the preceding 12 months
17. (For Part B trial) took part in the lixisenatide prandial dose-finding Part A trial
18. Felt to be unsuitable to participate in the trial in the opinion of the Principal Investigator
19. Currently taking domperidone, metoclopramide or warfarin

Recruitment start date

02/05/2014

Recruitment end date

04/01/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LJ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor type

University/education

Website

http://www.admin.ox.ac.uk/researchsupport/ctrg/

Funders

Funder type

Industry

Funder name

Sanofi Aventis (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data