Randomised, controlled, parallel-group prospective study to investigate the clinical effectiveness of early insulin treatment in patients with Latent Autoimmune Diabetes in Adults
| ISRCTN | ISRCTN63815121 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63815121 |
| EudraCT/CTIS number | 2006-004662-14 |
| ClinicalTrials.gov number | NCT00776607 |
| Secondary identifying numbers | EudraCT 2006-004662-14 AND S06 GenMed601 |
- Submission date
- 27/03/2007
- Registration date
- 10/05/2007
- Last edited
- 04/10/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Dr Sinead Brophy
Scientific
Scientific
School of Medicine
Swansea University
Singleton Park
Swansea
SA2 8PP
United Kingdom
| Phone | +44 (0)1792 602058 |
|---|---|
| s.brophy@swansea.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| 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 | Randomised, controlled, parallel-group prospective study to investigate the clinical effectiveness of early insulin treatment in patients with Latent Autoimmune Diabetes in Adults |
| Study acronym | LIT (LADA Insulin Trial) |
| Study hypothesis | Treatment for Latent Autoimmune Diabetes in Adults (LADA) should be that used for type 1 diabetes (insulin) rather than type 2 diabetes (tablets) in order to maintain glucose control (HbA1c) and natural insulin production (C-peptide). |
| Ethics approval(s) | Multi-Centre Research Ethics Committee (MREC) for Wales, 22/02/2007, ref: 07/MRE09/8 |
| Condition | Latent autoimmune diabetes in adults |
| Intervention | 1. Treatment group one - insulin: Patients will be given advice on diet, exercise and lifestyle and will be started on NovoMix 30, one dose of 6 U at the evening/main meal. Dose will be adjusted in increments of 2 - 6 U depending on fasting glucose level. Adjustment of breakfast and/or evening meal dose (i.e. evening dose for pre-breakfast glucose and morning dose for pre evening meal glucose) will be performed once a week as follows: a. Less than 3.0 Mmol/l or severe hypoglycaemia: -4 U b. 3.1 - 4.4 Mmol/l: -2 U c. 4.5 - 6.0 Mmol/l: No change d. 6.1 - 7.8 Mmol/l: +2 U e. 7.9 - 10.0 Mmol/l: +4 U f. Greater than 10.0 Mmol/l: +6 U When total dose equals 16 U patient will be started on 4 U with breakfast and continue with 16 units with evening meal. Breakfast and/or evening meal dose will be adjusted where necessary at increments of 2 - 6 U depending on fasting and/or pre-evening meal glucose level. Patient needs to keep a daily diary of insulin doses taken. 2. Treatment group two - tablets: a. Step one: patients not treated with tablets will be given a three months trial of lifestyle modification including advice on diet, exercise and smoking. If HbA1c remains above 7% patients will progress to step two. Patients will be progressed to step two if their General Practitioner (GP) has already put them on metformin (put in at number of metformin tables that GP has recommended) or sulphonylurea or if their baseline HbA1c is above 8% (patients will start on one 500 mg tablet per day). This means that sulphonylurea will be discontinued in all patients. Patients on step one will be progressed to step two before the three-month period if they have already had a three-month period of diet before starting the study AND during phone contact they report to be symptomatic (thirst, fatigue, polyuria) and unwell. In these cases, patients may be invited to attend clinic before the three-month period to be given metformin b. Step two: lifestyle modification and Metformin. If the patient has an HbA1c of 7% - 7.5% they start on 500 mg x 1 per day for the next three months. If the HbA1c is 7.6% - 8.0% they would start the first week on 500 mg x 1 day and then for the remaining period of the three months will take 500 mg x 2 per day. If the HbA1c is above 8.0% then patient will be on 500 mg x 3 per day. This will be titrated at the rate of 500 mg x 1 for the first week, 500 mg x 2 for the second week and 500 mg x 3 for the remaining time of the three-month period. If unable to tolerate metformin then the participant will be given Glucophage SR and if unable to tolerate this they will then progress to Step three. If HbA1c remains above 7% then those on one tablet per day will be moved to two tablets per day, those on two tablets per day will be moved to three tablets per day, those on three tablets per day will be move to maximum dose of 2 g per day. If after three months the HbA1c is above 7% even with maximum dose, then progress to Step three. If during telephone contact the patient reports symptoms then they may be titrated up. In summary, patients will be have their HbA1c evaluated every three months and will be titrated accordingly c. Step three: lifestyle modification and Glitazone (Roseglitazone). Patients with an HbA1c of above 7% will be given 4 mg once per day for three months. If after a three-month period the HbA1c remains above 7% then titrate to maximal dose of 4 mg twice per day with or without Metformin. If HbA1c remains above 7% for an additional three months then move to step four. Therefore, glitazone monotherapy will be used if Metformin intolerant otherwise glitazone will be added to the metformin (as per standard practice) d. Step four: lifestyle modification and insulin therapy (oral agents will be stopped). Titration will be based on fasting blood glucose level. The initiation of insulin will the same as for the insulin arm and will follow the protocol detailed above |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Metformin, glitazone, insulin |
| Primary outcome measure | To examine the effect of standard treatment for type one (insulin [NovoMix 30] therapy) compared to standard treatment for type two diabetes (tablets) on: 1. Change in fasting serum C-peptide level over 24 months in patients with LADA, and 2. Change in HbA1c level over 24 months in patients with LADA |
| Secondary outcome measures | To assess the effect of standard type one treatment (insulin) on: 1. Average number of times the fasting plasma glucose level is above 8 mmol/l (141 mg/dl) 2. Quality of life 3. Proportion of patients with insulin dependence (as judged by C peptide level) 4. GAD antibody level 5. Homeostasis Model Assessment (HOMA) 6. Adverse events (particularly hypoglycaemic events) 7. Weight/blood pressure/total cholesterol and inflammatory markers in LADA patients compared to standard type two diabetes treatment |
| Overall study start date | 01/06/2007 |
| Overall study end date | 01/06/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 210 |
| Participant inclusion criteria | 1. Male, non-fertile female (i.e., post menopausal, post hysterectomy, or sterilised by tubal ligation) or female of childbearing potential using a medically approved birth control method 2. The patient has a diagnosis of diabetes mellitus according to World Health Organisation (WHO) classification 3. The patient has a positive Glutamic Acid Decarboxylase (GAD) antibody test of 101 units or more on two separate occasions 4. Aged 18 years or more 5. Not on insulin within one month of diagnosis 6. Written informed consent to participate in the study 7. Ability to comply with all study requirements |
| Participant exclusion criteria | 1. Pregnant or breast-feeding females and females who plan pregnancy or breast-feeding during the course of the study 2. A history of: 2.1. Diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly 2.2. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past six months 3. Acute infections, which may affect blood glucose control within four weeks prior to visit one 4. Malignancy including leukaemia and lymphoma (not including basal cell skin cancer) within the last five years 5. The patient has a known immune deficiency from any disease, or a condition associated with an immune deficiency 6. The patient is receiving immunosuppressive or immunomodulating agents or cytotoxic therapy, or any medication that, in the opinion of the site investigator, might interfere with the study 7. Any of the following significant laboratory abnormalities: 7.1. Patients with severe renal failure as defined previous renal transplant or currently having renal dialysis or Glomerular Filtration Rate (GFR) less than 30 7.2. Clinically significant laboratory abnormalities, confirmed by repeat measurement, that may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycaemia and glycosuria at visit one 7.3. Severe ketonuria (+++ on urine sticks testing; ++ on repeated urine sticks testing) 8. The patient is a known or suspected drug abuser 9. The patient has chronic hepatitis or liver cirrhosis, or any other chronic liver disease 10. The patient is known to test positive for hepatitis B antigens or hepatitis C antibodies 11. The patient is known to test positive for Human Immunodeficiency Virus (HIV) antibodies 12. The patient has any significant diseases or conditions, including psychiatric disorders and substance abuse that, in the opinion of the site investigator, are likely to affect the patient's response to treatment or their ability to complete the study 13. The patient has chronic haematological disease 14. The patient has had a severe blood loss (greater than or equal to 400 mL, e.g., blood donation) within two months before the first dosing of the study medication 15. The patient has known proliferative retinopathy 16. Patient has had stage three to four heart failure 17. The patient is participating in another research study which may affect the results of this trial |
| Recruitment start date | 01/06/2007 |
| Recruitment end date | 01/06/2011 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
School of Medicine
Swansea
SA2 8PP
United Kingdom
SA2 8PP
United Kingdom
Sponsor information
Swansea NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Central Clinic
Trinity Buildings
21 Orchard Street
Swansea
SA1 5AT
Wales
United Kingdom
| jemma.hughes@swansea-tr.wales.nhs.uk | |
| Website | http://www.swansea-tr.wales.nhs.uk/ |
"ROR" |
https://ror.org/04zet5t12 |
Funders
Funder type
Industry
Novo Nordisk Ltd (UK)
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? |
|---|---|---|---|---|---|
| Protocol article | protocol | 24/07/2008 | Yes | No | |
| Results article | results | 01/07/2011 | Yes | No |
Editorial Notes
04/10/2018: Publication reference added.
