Diabetes Mellitus, Non-Insulin-DependentPhase 2/3NCT02662400
Assessment of Insulin Sensitivity and β Cell Function by Clamps Studies
A Phase 2/3 study testing MNCs in people with Diabetes Mellitus, Non-Insulin-Dependent, run by Post Graduate Institute of Medical Education and Research, Chandigarh.
Trial summary
India is the "Diabetes Capital of the World" with 41 million Indians having diabetes i.e. every fifth diabetic in the world is an Indian. Type 2 Diabetes Mellitus (T2DM) constitutes the major chunk of diabetes and has insulin resistance as the hallmark feature in the pathogenesis. Read more about this study
- Who is it for?
- Ages 30 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Non-Insulin-Dependent
- What is being tested?
- MNCs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Dec 2016
- 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 30 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Failure to triple oral hypoglycemic agent and on stable doses of insulin for at least 3 months.
- On vildagliptin,pioglitazone and metformin for at least 3 months along with Insulin to maintain euglycemia.
- HbA1c < 7.5%.
- Insulin requirement ≥0.4 IU/kg/d.
- GAD antibody negative status.
Who cannot join
- Patients with type 1 diabetes mellitus or secondary diabetes.
- Patients with serum creatinine > 1.5 mg/dl.
- Abnormal liver function tests (defined as value of transaminases > 3 times the upper value of normal or serum bilirubin higher than normal for the reference value for the laboratory).
- History of cholecystitis/ cholelithiasis/cholecystectomy.
- Seropositivity for HIV, HBsAg and hepatitis C virus (HCV).
- History of myocardial infarction or unstable angina in the previous 3 months.
- History of malignancy.
- Patients with active infections.
About this study
Official title: Assessment of Insulin Sensitivity and β Cell Function by Clamps Studies After Stem Cell Transplantation in T2DM
India is the "Diabetes Capital of the World" with 41 million Indians having diabetes i.e. every fifth diabetic in the world is an Indian. Type 2 Diabetes Mellitus (T2DM) constitutes the major chunk of diabetes and has insulin resistance as the hallmark feature in the pathogenesis. However, with the progression of the disease the insulin resistance becomes stable whereas β - cell function shows a gradual decline due to its ongoing apoptosis. This ultimately leads to inability of the β - cells to cope up with the increased demand of insulin caused due to insulin resistance and manifests as hyperglycemia. As β - cell failure is progressive and inexorable, as demonstrated in United Kingdom Prospective Diabetes Study, most of the patients with T2DM would eventually require insulin and it would be difficult to achieve to attain a strict glycemic control . It is well known that diabetes related complications which account for morbidity and mortality in this disease can be prevented or delayed by strict glycemic control. However, even with intensive insulin therapy it has been shown that glycemic control can never be perfect with patients exhibiting hyperglycemia or hypoglycemia during 24 hour glucose profile. Also insulin therapy is not physiological as there is no hepatic "first - pass" metabolism of insulin which is required for halting the hepatic glucose output, which is responsible for fasting hyperglycemia. This led the researchers to evolve various strategies of β - cell replacement therapy e.g. pancreatic transplantation and islet cell transplantation. Initially the results of islet cell transplantation were dismal but after the induction of glucocorticoid free immunosuppressive therapy and the use of adequate number of islet cells from multiple donors, the results of islet cell transplantation have been better. However, islet cell transplantation has its own limitations viz insufficient supply, being technically demanding and requirement of lifelong immunosuppressive therapy in the recipient.
Read the detailed description
The shortcomings can be overcome by the use of stem cells which is an inexhaustible source of β -cells. Stem cells are primitive cells capable of differentiating into mature cells of the body of various lineages. Stem cells can be obtained from various sources like blastocyst (embryonal stem cells), umbilical cord or bone marrow. There is an evidence to suggest that stem cell transplantation can lead to improvement in pancreatic endocrine function and improvement in glycemic control in diabetic mice through various mechanisms such as transdifferentiation or regeneration of endothelial cell in the damaged islets which in turn lead to regeneration of islet cells by paracrine action. However, till date there is no study that demonstrates that stem cell therapy can be effective in patients with T2DM for their glycemic control.
The investigators propose to carry out autologous bone marrow - derived stem cell transplantation (ABMSCT) in patients of T2DM, obtained from their own bone marrow and its superselective injection into the gastroduodenal artery after purification without any immunosuppressive regimen.
- Conditions
- Diabetes Mellitus, Non-Insulin-Dependent
- Being tested
- MNCs
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MNCsBiological
200 - 300 ml of bone marrow will be aspirated and layered on density gradient medium (Ficoll - hypaque ) and stem cells will be separated. Separated mono nucleated cells will injected into superior pancreatico duodenal artery. Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide HYPERGLYCEMIC CLAMP FOR ASSESSMENT OF BETA CELL FUNCTION , AND EUGLYCEMIC CLAMP TO ASSESS INSULIN SENSITIVITY .Homeostasis Model of Assessment - Insulin Resistance and Beta cell function ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months
| Study group | Role | What they receive |
|---|---|---|
| MNCs GROUP | Experimental | Patients with Type 2 Diabetes mellitus Receives: Biological: MNCs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in insulin sensitivity after stem cell transplantation
Stem cells will be transplanted in patients with T2DM. Pre and Pro stem cell transplantation Insulin sensitivity(pmol/l) will be assessed by euglycemic clamp .
Measured: 6 months
Secondary outcomes (1)
Improvement in β cell function after stem cell transplantation
Stem cells will be transplanted in patients with T2DM. Pre and Pro stem cell transplantation β cell function(nmol/L) will be assessed by hyperglycemia clamp .
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2016 (estimated)
- Study startJan 2016
- Primary completionOct 2016
- Study completionDec 2016
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, Non-Insulin-DependentStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anil Bhansali, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- anil Bhansali, DM, Principal investigator, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02662400
- Sponsor's protocol ID
- MNCs IN Diabetes
- Status last verified
- Jan 2017
- First submitted
- 10 Jan 2016
- Last updated
- 18 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Bhansali A, Asokumar P, Walia R, Bhansali S, Gupta V, Jain A, Sachdeva N, Sharma RR, Marwaha N, Khandelwal N. Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study. Cell Transplant. 2014;23(9):1075-85. doi: 10.3727/096368913X665576.
PubMed 23561959
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Insulin Sensitivity and β Cell Function by Clamps Studies After Stem Cell Transplantation in T2DM
- ClinicalTrials.gov ID
- NCT02662400
- Acronym / sponsor ID
- MNCs IN Diabetes
- Conditions
- Diabetes Mellitus, Non-Insulin-Dependent
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 25 Jan 2016 (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.
India is the "Diabetes Capital of the World" with 41 million Indians having diabetes i.e. every fifth diabetic in the world is an Indian. Type 2 Diabetes Mellitus (T2DM) constitutes the major chunk of diabetes and has insulin resistance as the hallmark feature in the pathogenesis. However, with the progression of the disease the insulin resistance becomes stable whereas β - cell function shows a gradual decline due to its ongoing apoptosis. This ultimately leads to inability of the β - cells to cope up with the increased demand of insulin caused due to insulin resistance and manifests as hyperglycemia. As β - cell failure is progressive and inexorable, as demonstrated in United Kingdom Prospective Diabetes Study, most of the patients with T2DM would eventually require insulin and it would be difficult to achieve to attain a strict glycemic control . It is well known that diabetes related complications which account for morbidity and mortality in this disease can be prevented or delayed by strict glycemic control. However, even with intensive insulin therapy it has been shown that glycemic control can never be perfect with patients exhibiting hyperglycemia or hypoglycemia during 24 hour glucose profile. Also insulin therapy is not physiological as there is no hepatic "first - pass" metabolism of insulin which is required for halting the hepatic glucose output, which is responsible for fasting hyperglycemia. This led the researchers to evolve various strategies of β - cell replacement therapy e.g. pancreatic transplantation and islet cell transplantation. Initially the results of islet cell transplantation were dismal but after the induction of glucocorticoid free immunosuppressive therapy and the use of adequate number of islet cells from multiple donors, the results of islet cell transplantation have been better. However, islet cell transplantation has its own limitations viz insufficient supply, being technically demanding and requirement of lifelong immunosuppressive therapy in the recipient.
Detailed description
The shortcomings can be overcome by the use of stem cells which is an inexhaustible source of β -cells. Stem cells are primitive cells capable of differentiating into mature cells of the body of various lineages. Stem cells can be obtained from various sources like blastocyst (embryonal stem cells), umbilical cord or bone marrow. There is an evidence to suggest that stem cell transplantation can lead to improvement in pancreatic endocrine function and improvement in glycemic control in diabetic mice through various mechanisms such as transdifferentiation or regeneration of endothelial cell in the damaged islets which in turn lead to regeneration of islet cells by paracrine action. However, till date there is no study that demonstrates that stem cell therapy can be effective in patients with T2DM for their glycemic control.
The investigators propose to carry out autologous bone marrow - derived stem cell transplantation (ABMSCT) in patients of T2DM, obtained from their own bone marrow and its superselective injection into the gastroduodenal artery after purification without any immunosuppressive regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MNCs GROUP | Experimental | Biological: MNCsPatients with Type 2 Diabetes mellitus |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Failure to triple oral hypoglycemic agent and on stable doses of insulin for at least 3 months.
- On vildagliptin,pioglitazone and metformin for at least 3 months along with Insulin to maintain euglycemia.
- HbA1c < 7.5%.
- Insulin requirement ≥0.4 IU/kg/d.
- GAD antibody negative status.
Key exclusion criteria (8 listed)
- Patients with type 1 diabetes mellitus or secondary diabetes.
- Patients with serum creatinine > 1.5 mg/dl.
- Abnormal liver function tests (defined as value of transaminases > 3 times the upper value of normal or serum bilirubin higher than normal for the reference value for the laboratory).
- History of cholecystitis/ cholelithiasis/cholecystectomy.
- Seropositivity for HIV, HBsAg and hepatitis C virus (HCV).
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 |
|---|---|---|
| MNCs200 - 300 ml of bone marrow will be aspirated and layered on density gradient medium (Ficoll - hypaque ) and stem cells will be separated. Separated mono nucleated cells will injected into superior pancreatico duodenal artery. Patients will be urged to monitor and document blood glucose readings for next 6 months. Glucagon stimulated C - peptide HYPERGLYCEMIC CLAMP FOR ASSESSMENT OF BETA CELL FUNCTION , AND EUGLYCEMIC CLAMP TO ASSESS INSULIN SENSITIVITY .Homeostasis Model of Assessment - Insulin Resistance and Beta cell function ,HbA1c, lipid profile and biochemistry will be done at baseline and 6 months | Biological | MNCs GROUP |
Primary outcome
Improvement in insulin sensitivity after stem cell transplantation
Time frame: 6 months
Stem cells will be transplanted in patients with T2DM. Pre and Pro stem cell transplantation Insulin sensitivity(pmol/l) will be assessed by euglycemic clamp .
1 secondary outcome
Improvement in β cell function after stem cell transplantation
Time frame: 6 months
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 18 Jan 2017.
- Background: PubMed 23561959Bhansali A, Asokumar P, Walia R, Bhansali S, Gupta V, Jain A, Sachdeva N, Sharma RR, Marwaha N, Khandelwal N. Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study. Cell Transplant. 2014;23(9):1075-85. doi: 10.3727/096368913X665576.
- Individual participant dataSharing planned: No
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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.
anil Bhansali, DM principal investigator
Post Graduate Institute of Medical Education and Research, Chandigarh
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing MNCs in people with Diabetes Mellitus, Non-Insulin-Dependent, run by Post Graduate Institute of Medical Education and Research, Chandigarh.
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 8 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 18 Jan 2017. 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. 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?
Improvement in insulin sensitivity after stem cell transplantation (time frame: 6 months). 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 NCT02662400, 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 18 Jan 2017.