Plain English Summary
Background and study aims
Type 1 diabetes is a lifelong condition where the pancreas is unable to produce insulin, causing a person to have high or uncontrolled levels of blood sugar in their blood. It is a complex disease resulting from the autoimmune destruction of the majority of islet β-cells and requires patients to inject themselves with insulin to control their blood sugar. It is a major cause of morbidity (diseases) and mortality (death) worldwide. There is an option for stem cells to treat patients who are insulin dependent due to diabetes. Bone marrow is a diverse source of stem cells and transplantation could help repair and regenerate tissue that has been damaged. The normal way to deliver the stem cells (through injections into the arteries) has many problems. There is a possibility that taking stem cells from bone marrow and injecting it back into the person’s pancreas could be feasible. The aim of this study is to evaluate the safety of a new strategy (designed to enhance the localization of where cells are injected to the diseased pancreas) by a single administration of autologus bone marrow derived mononuclear cells (A-BMMNCs) (that have certain types of stem cells) using a computed tomography (CT) scan-guided direct delivery route and to explore whether this treatment leads to improved β-cell function in diabetes patients.
Who can participate?
Males and females aged two to 30 years old with confirmed Type 1 diabetes.
What does the study involve?
Participants undergo a clinical examination and provide blood samples. They then undergo a bone marrow transplant done using a new strategy that uses a single administration of stem cells from bone marrow to a certain part of the pancreas (directly to the tail, not to the blood vessels that supply the pancreas). This is guided by a CT scanning machine. Participants are followed up for one year to see if there was any improvement or decrease in their β-cell function and diabetes symptoms.
What are the possible benefits and risks of participating?
Participants may benefit from being able to decrease or stop injecting insulin and having less diabetes complications. There is a risk of acute pancreatitis.
Where is the study run from?
Wadi EL-Neel Hospital (JCI) (Egypt)
When is the study starting and how long is it expected to run for?
January 2014 to June 2015
Who is funding the study?
Wadi EL-Neel Hospital (JCI) (Egypt)
Who is the main contact?
Professor Hazem Khamis
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
0000006555
Study information
Scientific title
A preliminary safety and efficacy evaluation of direct intrapancreatic tail delivery of autologous bone marrow-derived cells in Egyptian patients with type 1 diabetes mellitus
Acronym
Study hypothesis
The aim of this study is to evaluate the safety of a new strategy (designed to enhance localization of the injected cells to the diseased pancreas along with avoidance of nonspecific organ entrapment) by a single administration of autologus bone marrow derived mononuclear cells (A-BMMNCs) via a computed tomography (CT) scan-guided direct transgastricintrapancreatic (DTI) delivery route and to explore whether this treatment leads to improved β-cell function in insulin dependent diabetes mellitus (IDDM) patients.
Ethics approval
Wadi El-neel Ethical Committee, 13/01/2014, ref: 0000006555
Study design
Prospective single centre interventional non randomised study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet’
Condition
Type 1 diabetes mellitus
Intervention
At baseline, participants undergo a clinical examinations and provide blood samples to assess for HbA1c, fasting C-peptide (FCP) and 2hour-C-peptide (2h-CP) levels (as indirect measures of endogenous insulin secretion), levels of islet cells and insulin antibodies. Insulin doses for each participant are determined.
Participants then undergo an autologus bone marrow transplant derived mononuclear cells. This is done using a new strategy (designed to enhance localisation of the injected cells to the diseased pancreas along with the avoidance of nonspecific organ entrapment) by a single administration of bone marrow-derived mononuclear cells (BM-MNCs) via a computed tomography (CT) scan-guided direct transgastricintrapancreatic (DTI) delivery route.
During the procedure, participants are assessed for bleeding from the bone marrow aspiration and transgastric puncture sites, abdominal pain and other clinical complaints (i.e. nausea, vomiting, pain and fever). Blood amylase levels are measured to exclude acute pancreatitis complications. Haematocrit values are obtained only in suspected bleed cases.
Participants are followed up between month one-two, three-five, six-eight, and after eight months (around 12 months) for any clinical complaints. After six months, if islet cells and insulin antibodies are abnormal and serologically positive before the transplantation, there are re-measured to record any improvement or decline in these antibodies. If the patients are negative for islet cell or insulin antibodies before the transplantation, the test is not repeated after six months (as it is not recommended as routine clinical practice). Participants are also followed up to measure their HbA1c, FCP, 2h-CP, insulin doses levels as well as their frequency of hospitalisation for hypo- and hyper-glycemic attacks (common acute short-term complications of uncontrolled diabetes that can lead to hospitalization and account for the majority of costs associated with diabetes care). Participants are encouraged to self-monitor blood glucose at least twice a day.
Intervention type
Drug
Phase
Not Applicable
Drug names
Insulin, autologus bone marrow derived mononuclear cells
Primary outcome measure
Safety is measured using the morbidity, mortality, and unwanted side effects (through patient records) during the procedure and at 12 month follow up.
Secondary outcome measures
1. Serological changes in positive islet cell and insulin antibody levels are measured using blood samples at baseline and six months
2. β-cell function is measured using blood samples( HbA1c and in FCP and 2h-CP levels) at baseline, month one-two, month three-five, month six-eight and months eight to 12
3. Abdominal pain and other clinical parameters are measured using clinical examination during the procedure and at month one-two, month three-five, month six-eight and month 12
Overall trial start date
13/01/2014
Overall trial end date
13/06/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males and females aged between 2 to 30 years of age
2. Confirmed T1D based on the American Diabetes association (ADA) 2015 criteria for diagnosis
3. Body mass index (BMI) of ≤ 29.9
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
as large sample size as we can
Participant exclusion criteria
1. Active infections
2. Any chronic or acute illness
3. Antibodies to hepatitis B surface antigen
4. Hepatitis C
5. Human immunodeficiency virus or evidence of diabetic complications at baseline
6. Pregnant, are breast-feeding or intend to become pregnant during the study
7. Clinically relevant uncontrolled medical conditions not associated with diabetes (such as hematologic, renal, hepatic, neurologic, cardiac and respiratory conditions)
8. Evidence of active malignancy or a prior history of active malignancy
Recruitment start date
13/02/2014
Recruitment end date
13/04/2014
Locations
Countries of recruitment
Egypt
Trial participating centre
Wadi El-neel (JCI Accredited Hospital)
Kobri Elkobba
Cairo
19303
Egypt
Funders
Funder type
Hospital/treatment centre
Funder name
Wadi EL-Neel Hospital (JCI)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a peer reviewed high-impact journal.
IPD sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request from Raghda Moustafa Shahin at Raghda.shahin@fop.usc.edu.eg
Intention to publish date
31/05/2017
Participant level data
Available on request
Basic results (scientific)
Publication list