Effect of Change in T1DM Glycemic ControlPhase 2/3NCT04879511
Effect of Metformin in Children With Type 1 Diabetes
A Phase 2/3 study testing metformin and Basal/bolus insulin in people with Effect of Change in T1DM Glycemic Control, run by Ain Shams University at 1 site in Egypt.
Trial summary
Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Effect of Change in T1DM Glycemic Control
- What is being tested?
- metformin and Basal/bolus insulin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 10 Feb 2018to 29 Jan 2021
- Phase
- Phase 2/3
- 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 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with type 1 diabetes mellitus (5 years duration at least) and with micro-vascular complications.
- Patients on regular visits to clinic.
- Patients on regular insulin therapy.
Who cannot join
- Any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Metformin on Circulating Neuregulin-4 in Children With Type 1 Diabetes
Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1DM have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1DM. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes mellitus (T2DM) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2DM for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1DM.
This is the first study to study effect of metformin on circulating neuregulin-4 levels as a marker for subclinical atherosclerosis.
Read the detailed description
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.
The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention. Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.
Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.
The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention . Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.
Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing careers and families is particularly detrimental .
Neuregulin 4 (Nrg4), a recently identified adipokine, has been found in multiple organs, in particular brown adipose tissue (BAT), and belongs to the epidermal growth factor (EGF) family of extracellular ligands. Overexpression of Nrg4 can reduce chronic inflammation through inhibiting the gene expression of macrophage marker monocyte chemotactic protein 1 (Mcp1) and enhancing the expression of M2 macrophage marker gene Cd163, demonstrating that Nrg4 may possess anti-inflammatory and anti-atherogenic properties. Lower Nrg4 levels have been reported to be associated with the percentage of body fat mass, liver fat content, obesity, IR, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) .
Moreover, serum Nrg4 levels have been reported to be inversely associated with subclinical cardiovascular disease (CVD) in obese adults.
Recent studies reveal that neuregulin.4 may be closely associated with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Many lines of evidence indicate that inflammation is closely associated with atherosclerosis and plays a crucial role in the development of CVD.
Biguanides sensitize body cells to insulin, which may cause a reduction of atherogenic lipid fractions in patients with type 2 diabetes.
- Being tested
- metformin, Basal/bolus insulin
- Keywords
- Neuregulin-4, metformin, Type 1 diabetes
- 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
Also called Glucophage
Oral hypoglycemic drug metformin
Basal/bolus insulinDrug
Basal/bolus insulin
| Study group | Role | What they receive |
|---|---|---|
| Receiving metformin | Active comparator | Active group receiving metformin with basal /bolus insulin Receives: Drug: metformin; Drug: Basal/bolus insulin |
| Placebo | Placebo comparator | Control group receiving Placebo with basal/bolus insulin Receives: Drug: Basal/bolus insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycemic control(HbA1c%)
Effect of metformin supplementation on Glycemic control(HbA1c%)
Measured: up to 24 weeks
Secondary outcomes (1)
circulating neuregulin-4 level
Effect of metformin supplementation on level of circulating neuregulin-4
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start10 Feb 2018
- Primary completion1 Jan 2021
- Study completion29 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Effect of Change in T1DM Glycemic ControlStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy Samir Elbarbary, Ain Shams University
- Investigators
- Nancy S Elbarbary, MD.PhD, Principal investigator, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04879511
- Sponsor's protocol ID
- Ain shams Pediatrics 2102018
- Status last verified
- May 2021
- First submitted
- 30 Apr 2021
- Last updated
- 10 May 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen Q, Thompson J, Hu Y, Das A, Lesnefsky EJ. Metformin attenuates ER stress-induced mitochondrial dysfunction. Transl Res. 2017 Dec;190:40-50. doi: 10.1016/j.trsl.2017.09.003. Epub 2017 Sep 28.
PubMed 29040818Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, Wan LM. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev. 2017 May;33(4). doi: 10.1002/dmrr.2870. Epub 2016 Dec 27.
PubMed 27862843Kocak MZ, Aktas G, Erkus E, Yis OM, Duman TT, Atak BM, Savli H. Neuregulin-4 is associated with plasma glucose and increased risk of type 2 diabetes mellitus. Swiss Med Wkly. 2019 Oct 27;149:w20139. doi: 10.4414/smw.2019.20139. eCollection 2019 Oct 21.
PubMed 31656034
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin on Circulating Neuregulin-4 in Children With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04879511
- Acronym / sponsor ID
- Ain shams Pediatrics 2102018
- Keywords
- Neuregulin-4, metformin, Type 1 diabetes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 10 Feb 2018 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 29 Jan 2021 (actual)
- First posted
- 10 May 2021 (actual)
- 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.
Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1DM have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1DM. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes mellitus (T2DM) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2DM for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1DM.
This is the first study to study effect of metformin on circulating neuregulin-4 levels as a marker for subclinical atherosclerosis.
Detailed description
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.
The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention. Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.
Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.
The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention . Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.
Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing careers and families is particularly detrimental .
Neuregulin 4 (Nrg4), a recently identified adipokine, has been found in multiple organs, in particular brown adipose tissue (BAT), and belongs to the epidermal growth factor (EGF) family of extracellular ligands. Overexpression of Nrg4 can reduce chronic inflammation through inhibiting the gene expression of macrophage marker monocyte chemotactic protein 1 (Mcp1) and enhancing the expression of M2 macrophage marker gene Cd163, demonstrating that Nrg4 may possess anti-inflammatory and anti-atherogenic properties. Lower Nrg4 levels have been reported to be associated with the percentage of body fat mass, liver fat content, obesity, IR, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) .
Moreover, serum Nrg4 levels have been reported to be inversely associated with subclinical cardiovascular disease (CVD) in obese adults.
Recent studies reveal that neuregulin.4 may be closely associated with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Many lines of evidence indicate that inflammation is closely associated with atherosclerosis and plays a crucial role in the development of CVD.
Biguanides sensitize body cells to insulin, which may cause a reduction of atherogenic lipid fractions in patients with type 2 diabetes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Receiving metformin | Active comparator | Drug: metformin, Drug: Basal/bolus insulinActive group receiving metformin with basal /bolus insulin |
| Placebo | Placebo comparator | Drug: Basal/bolus insulinControl group receiving Placebo with basal/bolus insulin |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Patients with type 1 diabetes mellitus (5 years duration at least) and with micro-vascular complications.
- Patients on regular visits to clinic.
- Patients on regular insulin therapy.
Key exclusion criteria (1 listed)
- Any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases.
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 |
|---|---|---|
| metforminAlso: GlucophageOral hypoglycemic drug metformin | Drug | Receiving metformin |
| Basal/bolus insulinBasal/bolus insulin | Drug | Placebo, Receiving metformin |
Primary outcome
Glycemic control(HbA1c%)
Time frame: up to 24 weeks
Effect of metformin supplementation on Glycemic control(HbA1c%)
1 secondary outcome
circulating neuregulin-4 level
Time frame: up to 24 weeks
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 10 May 2021.
- Background: PubMed 29040818Chen Q, Thompson J, Hu Y, Das A, Lesnefsky EJ. Metformin attenuates ER stress-induced mitochondrial dysfunction. Transl Res. 2017 Dec;190:40-50. doi: 10.1016/j.trsl.2017.09.003. Epub 2017 Sep 28.
- Background: PubMed 27862843Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, Wan LM. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev. 2017 May;33(4). doi: 10.1002/dmrr.2870. Epub 2016 Dec 27.
- Background: PubMed 31656034Kocak MZ, Aktas G, Erkus E, Yis OM, Duman TT, Atak BM, Savli H. Neuregulin-4 is associated with plasma glucose and increased risk of type 2 diabetes mellitus. Swiss Med Wkly. 2019 Oct 27;149:w20139. doi: 10.4414/smw.2019.20139. eCollection 2019 Oct 21.
- Individual participant dataSharing planned: No
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.
Nancy S Elbarbary, MD.PhD principal investigator
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing metformin and Basal/bolus insulin in people with Effect of Change in T1DM Glycemic Control, run by Ain Shams University at 1 site in Egypt.
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 3 inclusion and 1 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 10 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Glycemic control(HbA1c%) (time frame: up to 24 weeks). 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 NCT04879511, which also lists 3 linked publications.
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 10 May 2021.