Umbilical Cord Blood Infusion to Treat Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT00305344
• Recruitment Status: Completed
• First Posted: March 21, 2006
• Results First Posted: July 10, 2012
• Last Update Posted: February 9, 2022
• Sponsor: University of Florida
• Collaborators: Juvenile Diabetes Research Foundation; National Institutes of Health (NIH)
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

While this study is now completely enrolled, we do hope to develop a "next generation" cord blood based study sometime in early 2009. Please continue to contact us if you have a child with newly diagnosed Type 1 Diabetes (T1D) who alo has their OWN cord blood in storage.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Procedure: Autologous Umbilical Cord Blood Transfusion; Biological: Cord blood	Phase 1; Phase 2

Detailed Description:

Objective:

Our goal is to transfuse autologous umbilical cord blood into 23 children with T1D in an attempt to re-establish immune tolerance and perhaps regenerate pancreatic islet insulin-producing beta cells and improve blood glucose control. As secondary goals, we aim to study the potential changes in metabolism/immune function leading to islet regeneration.

Background/Rationale:

Stem cells provide an exciting approach towards curing T1D. Autologous bone marrow transplants have been used successfully for patients undergoing high dose chemotherapy, and for a variety of cancers and autoimmune disorders such as multiple sclerosis, lupus, and rheumatic disorders. Recent studies in immunodeficient mice with chemically-induced pancreatic damage have shown that bone marrow-derived stem cells preferentially home to the pancreas and may have the capacity to initiate pancreatic regeneration, thereby restoring the endothelial interactions in the pancreas and correcting the associated elevated blood sugar levels Human umbilical cord blood cells transfused into a model of amyotrophic lateral sclerosis (ALS) resulted in delayed disease progression of two to three weeks and increased lifespan. Umbilical cord blood has shown promise as an excellent source for deriving stem cell populations, and has been used successfully in transplantation for a variety of diseases, including acute lymphocytic and myeloid leukemia, lymphoma, Fanconi anemia, and sickle cell disease. Furthermore, umbilical cord blood-derived stem cells have the capacity to differentiate into a variety of non-blood cell types, including hepatocytes, neural cells, and endothelial cells. In addition, umbilical cord blood contains a greater proportion of hematopoietic stem cells than bone marrow.

In addition, cord blood contains a large number of immune cells called regulatory T cells, These regulatory T cells may be helpful in diminishing autoimmunity. The need to re-establish tolerance in patients with established autoimmunity provides another potential mechanism for cord blood as a therapy for type 1 diabetes.

Description of Project:

23 children > 1 year of age with T1D and stored umbilical cord blood are being be recruited. The cord blood will be infused into the children in the GCRC in an attempt to regenerate pancreatic islet insulin-producing beta cells and improve blood glucose control. As secondary goals, we aim to track the migration of transfused cord blood stem and study the potential changes in metabolism/immune function leading to islet regeneration.

Anticipated Outcome:

It is hoped that there will be preservation of beta cell function assessed by mixed meal stimulated C-peptide secretion. Changes in immunological markers/function may be observed

Relevance to Type I Diabetes:

Type 1 diabetes is still associated with tremendous morbidity and premature mortality. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent complications. Unfortunately, there is presently no permanent cure for diabetes. Whole pancreas or islet cell transplantation is available only to a very limited number of patients and necessitates potential lifelong immunosuppressive therapy. The need to find a cure for T1D cannot be overstated -autologous stem cell transfusions either with their potential to differentiate into islet cells or provide immune tolerance that leads to islet regeneration appear to be a safe and potentially viable option.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Transfusion of Autologous Umbilical Cord Blood to Reverse Hyperglycemia in Children With Type 1 Diabetes - A Pilot Study
• Study Start Date: April 2005
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: May 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cord Blood; Umbilical Cord Blood	Procedure: Autologous Umbilical Cord Blood Transfusion; Cord Blood infusion; Other Name: Cord Blood; Biological: Cord blood; Develop Cord blood vaccine; Other Name: Vaccine

Outcome Measures

Primary Outcome Measures :

1. Children With T1D Underwent a Single Autologous UCB Transfusion [ Time Frame: Baseline to Year 2 ]
   All participants were monitored for 2 years. Baseline and post-infusion mixed meal tolerance tests were performed to determine whether autologous cord blood infusion preserved endogenous insulin production. The change in median area under the curve for C-peptide (measure of insulin production) from baseline to to 2 years during a 2 hour mixed meal tolerance test was used as the primary outcome measure and was reported in ng/ml/120 minutes

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Must have a diagnosis of T1D and have stored umbilical cord blood in an AABB and/or FACT accredited cord bank.
2. TID diagnosis will be defined as having a clear history of polydipsia, polyphagia, polyuria, and weight loss consistent with a clinical diagnosis, diagnosis will mot be based solely upon the presence of autoantibodies.
3. Cord blood meets all selection and testing criteria (see below).
4. Able to complete mixed meal tolerance / glucagon stimulation test.
5. Normal screening values for CBC, Renal function and electrolytes (BMP).
6. Willing to comply with intensive diabetes management

Exclusion Criteria:

1. Complicating medical issues that would interfere with blood drawing or monitoring.
2. Chronic use of steroids or other immunosuppressive agents for other conditions.
3. Positive infectious disease markers from mothers' blood or cord at time of collection (See below for details).
4. Any evidence of illness on planned infusion date (i.e. fever >38.5 C, vomiting, diarrhea, wheezing, or crackles).

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

Juvenile Diabetes Research Foundation

National Institutes of Health (NIH)

Investigators

• Principal Investigator: Michael J Haller, MD; University of Florida
• Principal Investigator: Desmond A Schatz, MD; University of Florida

More Information

Publications of Results:

Haller MJ, Wasserfall CH, Hulme MA, Cintron M, Brusko TM, McGrail KM, Sumrall TM, Wingard JR, Theriaque DW, Shuster JJ, Atkinson MA, Schatz DA. Autologous umbilical cord blood transfusion in young children with type 1 diabetes fails to preserve C-peptide. Diabetes Care. 2011 Dec;34(12):2567-9. doi: 10.2337/dc11-1406. Epub 2011 Oct 19.

Haller MJ, Wasserfall CH, McGrail KM, Cintron M, Brusko TM, Wingard JR, Kelly SS, Shuster JJ, Atkinson MA, Schatz DA. Autologous umbilical cord blood transfusion in very young children with type 1 diabetes. Diabetes Care. 2009 Nov;32(11):2041-6. doi: 10.2337/dc09-0967.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00305344
• Other Study ID Numbers: 1-2005-362; GCRC 593 ( Other Identifier: General Clinical Research Center ); UF IRB-01 125-2004 ( Other Identifier: UF Institutional Review Board )
• First Posted: March 21, 2006
• Results First Posted: July 10, 2012
• Last Update Posted: February 9, 2022
• Last Verified: February 2022

Keywords provided by University of Florida:

Type 1 Diabetes Mellitus; Umbilical Cord; Regeneration; Insulin; Islets of Langerhans

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs