Condition category
Nutritional, Metabolic, Endocrine
Date applied
14/09/2010
Date assigned
17/09/2010
Last edited
03/06/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Atir Khan

ORCID ID

Contact details

Diabetes Centre
Carmarthen
SA31 2AF
United Kingdom
+44 (0)1267 227508
atirsultanali.khan@wales.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

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

Acronym

Study hypothesis

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

Ethics approval pending

Study design

Double-blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information sheet available on request from Dr Atir Khan

Condition

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

Phase

Not Applicable

Drug names

Glucophage® SR (metformin [slow releasing formulation])

Primary outcome measures

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 trial start date

01/11/2010

Overall trial end date

01/11/2012

Reason abandoned

Participant recruitment issue

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

15 in each arm of the study (total 30)

Participant 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

Recruitment start date

01/11/2010

Recruitment end date

01/11/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

West Wales Hospital
Carmarthen
SA31 2AF
United Kingdom

Sponsor information

Organisation

West Wales Hospital (UK)

Sponsor details

Diabetes Centre
Carmarthen
SA31 2AF
United Kingdom
+44 (0)1267 227508
atirsultanali.khan@wales.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

West Wales Hospital (UK) - Diabetes Research fund

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

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes