The effect of lixisenatide in type 1 diabetes
| ISRCTN | ISRCTN00290196 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN00290196 |
| EudraCT/CTIS number | 2013-002259-14 |
| Secondary identifying numbers | 15724 |
- Submission date
- 03/04/2014
- Registration date
- 03/04/2014
- Last edited
- 21/06/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
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)
Contact information
Scientific
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
| Phone | +44 1865 857255 |
|---|---|
| irene.kennedy@dtu.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | The effect of lixisenatide in type 1 diabetes: a randomised controlled trial |
| Study acronym | LIXI |
| Study objectives | 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(s) | 13/LO/1656; First MREC approval date 10/01/2014 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 02/05/2014 |
| Completion date | 30/06/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | 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 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 02/05/2014 |
| Date of final enrolment | 04/01/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
OX3 7LJ
United Kingdom
Sponsor information
University/education
Research Services
Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Headington
Oxford
OX2 6HE
England
United Kingdom
| Website | http://www.admin.ox.ac.uk/researchsupport/ctrg/ |
|---|---|
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 21/06/2019 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
21/06/2019: Added clinicaltrialsregister.eu link to basic results (scientific). Added total final enrollment.
08/02/2016: The overall trial start and end dates have been updated from 14/04/201-11/01/2016 to 02/05/2014-30/06/2016 and the recruitment start and end dates have been updated from 14/04/201-11/01/2016 to 02/05/2016-04/01/2016. In addition, the inclusion criteria has been updated so that the age range of participants in 18-70 years rather than 18-65 years.
