Diabetes Mellitus, Type 1Phase 4NCT00118937
Effect of Metformin in Patients With Type-1 Diabetes With Inadequate Glycaemic Control by Insulin and Diet
A Phase 4 study testing Metformin in people with Diabetes Mellitus, Type 1, run by Steno Diabetes Center Copenhagen.
Trial summary
Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Dec 2003to Aug 2006
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HbA1c > 8.5% for more than one year prior to enrolment.
- Diabetes-duration > 5 years.
- Age at onset of diabetes < 35 years
- Fasting C-peptide < 300 pmol/l
- Age > 18 years at enrolment.
Who cannot join
- Clinical or biochemical signs of kidney-, liver- or heart-failure.
- Other coexisting serious morbidity, which will affect the study-participation or outcome of the study i.e. cancer.
- Known abuse of any medication or alcohol
- Hypoglycaemia unawareness.
- Pregnancy or planned pregnancy in the study-period.
About this study
Official title: Effect of Metformin On Glycaemic Control and Non-Glycaemic Cardiovascular Risk-Factors in Patients With Type-1 Diabetes, With Long-Standing Inadequate Glycaemic Control by Insulin and Diet
Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. The Diabetes Control and Complications Trial (DCCT)-study showed, that improved glycaemic control can prevent the development and progression of these late-diabetic complications. Until now treatment with insulin- and diet-therapy has been the only treatment-modalities available to improve the glycaemic control in patients with type-1-diabetes. A substantial number of these patients still have long-standing poor glycaemic control despite intensive treatment with insulin- and diet-therapy.
The antidiabetic drug metformin has shown to be able to improve the glycaemic control in combination with insulin and furthermore reduce both mortality and the risk of developing cardiovascular disease in patients with type-2-diabetes.
Read more
Only few small studies have investigated the effect of treatment with metformin in patients with type-1-diabetes. These studies have suggested a positive effect of metformin in these patients too.
Method:
100 patients with type-1-diabetes with persistent poor glycaemic control i.e. HbA1c > 8.5% during the last 12 months are eligible. Patients are treated for one month with placebo. Hereafter half of the patients will be treated with metformin and the other half continues with placebo for 12 months both as add-on therapy. All patients are continuing ongoing treatment with insulin throughout the study. Before and after the start of treatment with metformin the effect on glycaemic control and other known risk-factors for development of cardiovascular disease i. e. blood-pressure, fasting lipids, urine-albumine-excretion, endothelial dysfunction, inflammation, fibrinolysis etc. is assessed.
This study will show if treatment with metformin can improve the glycaemic control and hereby the prognosis of patients with type-1-diabetes with persistent poor glycaemic control despite intensive treatment with insulin- and diet-therapy. This group of patients suffers the highest risk of developing late-diabetic complications with reduced quality of life and life-expectancy as a consequence.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Metformin, Placebo.
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).
Placebo.Drug
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.
Placebo.Drug
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Single-blind placebo run-in period. Duration one month. Receives: Drug: Placebo. |
| 2 | Active comparator | Metformin 2000 mg, double-masked randomized during 12 months. Receives: Drug: Metformin |
| 3 | Placebo comparator | Placebo, double-masked randomized during 12 months. Receives: Drug: Placebo. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HbA1c - difference between final visit and baseline.
Secondary outcomes (17)
Absolute HbA1c
Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.
Insulin-dose
The following parameters are measured at baseline and at the final visit after 12 months of intervention:
Plasma-PAI-antigen and -activity, t-PA-antigen- and activity.
Plasma-fibrinogen
Serum-albumin
Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin.
Plasma-homocysteine
Asymmetric DiMethylArginine - ADMA
Urine-albumin-excretion in three 24 hour urine-collections
Blood-pressure in the sitting position after 10 minutes of rest.
Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100.
Weight, BMI and Waist-hip-ratio
White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa.
Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration.
Extra blood- and urine-samples will be stored at -80 degrees Celsius for potential extra analyses after closure of the study. DNA will be stored for later pharmaco-genetic analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2005 (estimated)
- Study startDec 2003
- Primary completionAug 2006
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Investigators
- Allan A Vaag, M.D., chief physician, Study chair, Steno Diabetes Center CopenhagenSoeren S Lund, M. D., Principal investigator, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00118937
- Sponsor's protocol ID
- Type-1-Metformin
- Status last verified
- Dec 2008
- First submitted
- 1 Jul 2005
- Last updated
- 8 Dec 2008
- Results posted
- No
Publications
Lund SS, Tarnow L, Astrup AS, Hovind P, Jacobsen PK, Alibegovic AC, Parving I, Pietraszek L, Frandsen M, Rossing P, Parving HH, Vaag AA. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. PLoS One. 2008;3(10):e3363. doi: 10.1371/journal.pone.0003363. Epub 2008 Oct 9.
PubMed 18852875
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin On Glycaemic Control and Non-Glycaemic Cardiovascular Risk-Factors in Patients With Type-1 Diabetes, With Long-Standing Inadequate Glycaemic Control by Insulin and Diet
- ClinicalTrials.gov ID
- NCT00118937
- Acronym / sponsor ID
- Type-1-Metformin
- Conditions
- Diabetes Mellitus, Type 1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Study start
- Dec 2003
- Primary completion
- Aug 2006 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 12 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. The Diabetes Control and Complications Trial (DCCT)-study showed, that improved glycaemic control can prevent the development and progression of these late-diabetic complications. Until now treatment with insulin- and diet-therapy has been the only treatment-modalities available to improve the glycaemic control in patients with type-1-diabetes. A substantial number of these patients still have long-standing poor glycaemic control despite intensive treatment with insulin- and diet-therapy.
The antidiabetic drug metformin has shown to be able to improve the glycaemic control in combination with insulin and furthermore reduce both mortality and the risk of developing cardiovascular disease in patients with type-2-diabetes.
Only few small studies have investigated the effect of treatment with metformin in patients with type-1-diabetes. These studies have suggested a positive effect of metformin in these patients too.
Method:
100 patients with type-1-diabetes with persistent poor glycaemic control i.e. HbA1c > 8.5% during the last 12 months are eligible. Patients are treated for one month with placebo. Hereafter half of the patients will be treated with metformin and the other half continues with placebo for 12 months both as add-on therapy. All patients are continuing ongoing treatment with insulin throughout the study. Before and after the start of treatment with metformin the effect on glycaemic control and other known risk-factors for development of cardiovascular disease i. e. blood-pressure, fasting lipids, urine-albumine-excretion, endothelial dysfunction, inflammation, fibrinolysis etc. is assessed.
This study will show if treatment with metformin can improve the glycaemic control and hereby the prognosis of patients with type-1-diabetes with persistent poor glycaemic control despite intensive treatment with insulin- and diet-therapy. This group of patients suffers the highest risk of developing late-diabetic complications with reduced quality of life and life-expectancy as a consequence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: Placebo.Single-blind placebo run-in period. Duration one month. |
| 2 | Active comparator | Drug: MetforminMetformin 2000 mg, double-masked randomized during 12 months. |
| 3 | Placebo comparator | Drug: Placebo.Placebo, double-masked randomized during 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HbA1c > 8.5% for more than one year prior to enrolment.
- Diabetes-duration > 5 years.
- Age at onset of diabetes < 35 years
- Fasting C-peptide < 300 pmol/l
- Age > 18 years at enrolment.
Key exclusion criteria (5 listed)
- Clinical or biochemical signs of kidney-, liver- or heart-failure.
- Other coexisting serious morbidity, which will affect the study-participation or outcome of the study i.e. cancer.
- Known abuse of any medication or alcohol
- Hypoglycaemia unawareness.
- Pregnancy or planned pregnancy in the study-period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminTablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose). | Drug | 2 |
| Placebo.Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day. | Drug | 1 |
| Placebo.Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily. | Drug | 3 |
Primary outcome
HbA1c - difference between final visit and baseline.
17 secondary outcomes
Absolute HbA1c
Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.
Insulin-dose
The following parameters are measured at baseline and at the final visit after 12 months of intervention:
Plasma-PAI-antigen and -activity, t-PA-antigen- and activity.
Plasma-fibrinogen
Serum-albumin
Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin.
Plasma-homocysteine
Asymmetric DiMethylArginine - ADMA
Urine-albumin-excretion in three 24 hour urine-collections
Blood-pressure in the sitting position after 10 minutes of rest.
Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100.
Weight, BMI and Waist-hip-ratio
White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa.
Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration.
Extra blood- and urine-samples will be stored at -80 degrees Celsius for potential extra analyses after closure of the study. DNA will be stored for later pharmaco-genetic analysis.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2008.
- Derived from this study: PubMed 18852875Lund SS, Tarnow L, Astrup AS, Hovind P, Jacobsen PK, Alibegovic AC, Parving I, Pietraszek L, Frandsen M, Rossing P, Parving HH, Vaag AA. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. PLoS One. 2008;3(10):e3363. doi: 10.1371/journal.pone.0003363. Epub 2008 Oct 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan A Vaag, M.D., chief physician study chair
Steno Diabetes Center Copenhagen
Soeren S Lund, M. D. principal investigator
Steno Diabetes Center Copenhagen
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Diabetes Mellitus, Type 1, run by Steno Diabetes Center Copenhagen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2008. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HbA1c - difference between final visit and baseline.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00118937, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2008.