Advantage of using Glucophage® SR (a Metofrmin) in non-overweight patients with type-1 Diabetes to improve their glucose control
| ISRCTN | ISRCTN85760737 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85760737 |
| Secondary identifying numbers | N/A |
- Submission date
- 14/09/2010
- Registration date
- 17/09/2010
- Last edited
- 03/06/2015
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Atir Khan
Scientific
Scientific
Diabetes Centre
Carmarthen
SA31 2AF
United Kingdom
| Phone | +44 (0)1267 227508 |
|---|---|
| atirsultanali.khan@wales.nhs.uk |
Study information
| Study design | Double-blind randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Patient information sheet available on request from Dr Atir Khan |
| Scientific title | Effectiveness of Glucophage® SR as an adjunct to insulin in improving glycaemic control, without increasing the episodes of hypoglycaemia, in non-overweight patients with type 1 diabetes |
| Study objectives | To study the improvement in glycaemic control, without increasing the episodes of hypoglycemia, following the addition of Glucophage® SR (Merck Serono) as an adjunct to insulin in non-overweight patients with type 1 diabetes. |
| Ethics approval(s) | Ethics approval pending |
| Health condition(s) or problem(s) studied | Type 1 diabetes |
| Intervention | 1. Screening Visit: At the 'screening visit' patients will attend in fasting state (due to C-peptide levels collection on this visit) and be asked to sign a consent form and data will be collected on age, sex, height, weight, body mass index (BMI), duration of diabetes, total daily insulin dose and incidence of hypoglycemia. Blood samples will be taken for fasting blood glucose, fasting C-peptide levels, HbA1c, urea and electrolytes (U&E) and liver function tests (LFTs). A complete physical examination and fundoscopy will be done. If available, record of any recent Diabetic retinopathy screening or laser eye treatment will be sought from patient's hospital notes. Patients will be given education on how to do home glucose monitoring (HGM), will be given a HGM booklet and a glucometer. Patients will be advised to do HGM (pre-breakfast, pre-lunch, pre-evening meal and pre-bed) three days prior to every visit. In addition, patients will be asked check the blood glucose whenever they feel the symptoms of hypoglycemia (defined as capillary blood glucose < 4.0mmol/L with or without symptoms) and record it with date and time. 2. Run-in period: Patients will receive education about study and an assessment of patient's ability to comply with the protocol will be made. 3. Randomisation: Patients will attend in a non-fasting state and data will be collected on weight, body mass index (BMI), total daily insulin dose and incidence of hypoglycemia. Blood samples will be taken for HbA1c, U&E and LFTs. Records of hypoglycemia during 'run-in period' and HGM 3 days prior to randomization visit will be checked. Insulin dosages will be adjusted as required. Patients will be randomized (double blind) to receive: 3.1. Glucophage® SR 5..mg once daily for 1 week, then twice daily for 6 months 3.2. Placebo 4. Intervention period: Patients will attend at week-1 (day-7), week-2 (day-14) and week-3 (day-21). At each of these three visits the record of HGM will be reviewed and insulin dosages will be titrated as required. In addition, at visit week-1 (day-7) the Glucophage® SR will be increased to 500mg twice daily (BD) {or equivalent in the placebo arm}. On each visit the tolerability and side effects of Glucophage® SR will be evaluated and recorded. Patients can continue in the study only if they are able to tolerate a minimum dose of Glucophage® SR 500mg twice daily. Following the visit on week-3 (day-21), there will be a total of 6 visits every month from the date of randomisation visit. At each of these visits patients will attend in a non-fasting state and data will be collected on weight, body mass index (BMI), total daily insulin dose and incidence of hypoglycemia. Blood samples will be taken for HbA1c, U&E and LFTs. Records of hypoglycemia during every visit and HGM 3 days prior to every visit will be checked. Insulin dosages will be adjusted. At the end of study visit (1 week after final monthly visit) blood pressure and pulse will be checked and physical examination will be done to ensure the patient is doing well. Patients will be switched back to their pre-study medications 5. Follow up visit: During the follow up appointment in Diabetes clinic, approx 2 months post intervention, study results will be discussed and if the results are found favourable for Glucophage® SR as an adjunct to insulin in this group of patients, the patients will be offered to start this combination treatment Updated 03/06/2015: The trial has been stopped due to poor recruitment and an interim analysis that suggested no benefit in continuing the trial. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Glucophage® SR (metformin [slow releasing formulation]) |
| Primary outcome measure | Improvement in glycaemic control as a result of addition of Glucophage® SR compared with placebo. Assessed by measurement of HbA1c at screening, baseline and 1, 2, 3, 4, 5 and 6 months. |
| Secondary outcome measures | 1. Improvement in number of episodes of hypoglycemia in Glucophage® SR arm of study 2. Reduction in insulin dose in Glucophage® SR arm of the study All outcomes assessed at screening, baseline and 1, 2, 3, 4, 5 and 6 months. |
| Overall study start date | 01/11/2010 |
| Completion date | 01/11/2012 |
| Reason abandoned (if study stopped) | Participant recruitment issue |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 15 in each arm of the study (total 30) |
| Key inclusion criteria | 1. Male or female, Aged > 18 years In addition, patients should fulfil all the following criteria at the randomisation visit: 2. Type-1 Diabetic patients with C-peptide negative result at screening visit (defined as C-peptide concentration < 0.18nmol/L at a time when blood glucose level is > 5.0mmol/L) 3. Suboptimal glycaemic control (HbA1c 7.5% to 8.5% at screening visit) with or without history of mild hypoglycemia (defined as hypoglycemia not affecting cognitive function and not requiring third party intervention for reversal) 4. History of previous attempts to improve glycaemic control resulting in hypoglycemic episodes (history from hospital medical notes or directly from patients) 5. History of Diabetes for > 1 year 6. BMI 21 to 27 7. Willing and able to comply with the study protocol |
| Key exclusion criteria | 1. Previous History of myocardial infarction (MI) (in last 12months) 2. Congestive Cardiac Failure (New York Heart Association [NYHA] class III or IV) 3. Chronic kidney disease with estimated Glomerular Filtration Rate (eGFR) < 45mL/minute/1.73m2 4. Abnormal Alanine Aminotransferase (ALT) (> 3fold at baseline) 5. Hypoglycaemia symptoms unawareness 6. History of hypoglycemic episodes requiring 3rd party assistance for reversal 7. Uncontrolled Hypertension (BP > 180/100mmHg) 8. Pregnant OR likelihood of pregnancy during the study 9. Females who are breast feeding 10. Proliferative Diabetic retinopathy and / or laser treatment in last 12 months 11. History of Diabetic ketoacidosis, lactic acidosis and gasteroparesis 12. Previous or current treatment with metformin / Glucophage® SR 13. History of irritable bowel syndrome. 14. Previous intolerance to metformin or Glucophage® SR 15. History of weight loss in last 6 months 16. History of allergic or hypersensitivity reaction to Glucophage® SR or any insulin |
| Date of first enrolment | 01/11/2010 |
| Date of final enrolment | 01/11/2012 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
West Wales Hospital
Carmarthen
SA31 2AF
United Kingdom
SA31 2AF
United Kingdom
Sponsor information
West Wales Hospital (UK)
Hospital/treatment centre
Hospital/treatment centre
Diabetes Centre
Carmarthen
SA31 2AF
Wales
United Kingdom
| Phone | +44 (0)1267 227508 |
|---|---|
| atirsultanali.khan@wales.nhs.uk | |
"ROR" |
https://ror.org/01cs14q41 |
Funders
Funder type
Hospital/treatment centre
West Wales Hospital (UK) - Diabetes Research fund
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 |
