Cord Blood Plus Vitamin D and Omega 3s in T1D

• ClinicalTrials.gov Identifier: NCT00873925
• Recruitment Status: Completed
• First Posted: April 2, 2009
• Last Update Posted: April 4, 2013
• Sponsor: University of Florida
• Collaborators: Juvenile Diabetes Research Foundation; National Institutes of Health (NIH)
• Information provided by (Responsible Party): University of Florida

Tracking Information

• First Submitted Date: April 1, 2009
• First Posted Date: April 2, 2009
• Last Update Posted Date: April 4, 2013
• Study Start Date: March 2009
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 1, 2009): C-Peptide following the 1 year mixed meal tolerance test [ Time Frame: 1 year post cord blood infusion ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 1, 2009)

• DHA Level [ Time Frame: 1 year post randomization ]
• Vitamin D Level [ Time Frame: 1 year post randomization ]
• HbA1c and Insulin Dose [ Time Frame: 1 year post randomization ]
• Peripheral Blood T-cell assays [ Time Frame: 1 year post randomization ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cord Blood Plus Vitamin D and Omega 3s in T1D
• Official Title: Transfusion of Autologous Umbilical Cord Blood Plus Vitamin D and Omega 3 Fatty Acids to Preserve Beta Cell Function in Children With Recent Onset Type 1 Diabetes - A Pilot Study

Brief Summary

In this pilot study the investigators are trying to see if a single intravenous infusion of autologous (self) cord blood cells followed by 1 year of daily vitamin D and omega 3 fatty acid supplementation can preserve beta cell function (prolong "honeymoon") in children with type 1 diabetes. All subjects will continue to use insulin therapy as needed to maintain the best possible glucose control.

15 Subjects will be randomized such that 2 of every 3 (10 total) will receive cord blood plus vitamin D and Omega 3 while 1 of 3 (5 total) will serve as controls and will not receive cord blood, vitamin D, or Omega 3 supplementation.

The study will involve 5 visits over 1 year to the University of Florida

This study is a follow-up to our initial study of cord blood infusion alone in which 23 children received autologous cord blood. The initial study was 100% safe but additional studies like the one described above are needed to determine how to improve cord blood based therapy.

Detailed Description

Hypothesis: We hypothesize that the combination of intensive insulin therapy, autologous umbilical cord blood (UCB), Vitamin D, and Omega 3 fatty acids administered to children with T1D will preserve residual c-peptide when compared to children receiving intensive insulin therapy alone

Specific Aims:

1. Randomize 15 children with recent onset T1D and available autologous cord blood such that 10 receive a combination of intensive insulin therapy, autologous UCB infusion, and daily Vitamin D while 5 receive intensive insulin therapy alone
2. Document safety of combination therapy
3. Study potential changes in glucose metabolism
4. Study potential changes in immune function

Preliminary Studies: Our group has already performed autologous cord blood infusion in 23 children with T1D and has documented the safety of this approach. While conclusive data regarding the efficacy of the infusion in preserving beta cell function are lacking, our pilot study has demonstrated a potential for cord blood to low the rate of c-peptide decline (a measure of beta cell function/mass) in these young children with T1D. As documented above, considerable work both here and other institutions suggests the potential for a combination of Vitamin D and DHA to further augment the autoimmune response. Given the safety and potential efficacy of such an approach, we feel that a pilot study of the combination of UCB infusion, vitamin D supplementation, and DHA supplementation is warranted.

Screening: Only subjects who are still making at least a small amount of detectable insulin will be eligible for this study. To determine if a child is still making insulin, they will undergo a mixed meal tolerance test. This involves placing an IV in the morning prior to eating. The subject then drinks a "mixed meal" (the nutritional supplement Boost is used)and blood is taken via the IV at timepoints over the next 2 hours to determine if insulin is still being produced.

Randomization: If a potential subject "passes" the screening test, they will then be randomized to either receiving the study intervention or to being a control. Subjects WILL be told what arm of the study they are randomized to.

Infusion: Those randomized to infusion will return to the University of Florida for a single autologous cord blood infusion and will be given vitamin D and Omega 3 supplements

Follow-up: Both Control and Intervention subjects will return at 3, 6, and 12 months after the infusion/screening visit to have blood drawn for a repeat mixed meal tolerance test, measurement of HbA1c, and other immune studies.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 1 Diabetes

Intervention

• Biological: Autologous UCB
  Umbilical Cord Blood stem cells CAN be collected and frozen immediately after birth in private and public cord blood banks. If a child with recent onset T1D has their OWN cord blood in storage they may qualify for this study. The cells would be released to the University of Florida where we would perform a single IV infusion of the cells once they have been thawed and washed. Depending on how the cells are stored, it may be possible to keep some portion of the cells in storage for future use.
• Dietary Supplement: Omega 3 FA
  Omega 3 Fatty Acids commonly found in fish oil may play an important role in preserving beta cell function via their anti-inflammatory actions. Those subjects randomized to treatment will take a daily supplement supplied as a capsule that can either be swallowed whole or opened so the contents can be mixed with food.
• Dietary Supplement: Vitamin D
  Vitamin D is important for calcium absorption and bone health but may also play an important role in promoting healthy immune responses. Subjects randomized to intervention will take vitamin D supplied as a liquid in a dropper (1 drop per day added to food) for 1 year.

Study Arms

• Experimental: Autologous UCB Plus Vit D Omega 3 FA
  A single autologous (self) intravenous umbilical cord blood infusion followed by 1 year of daily Vitamin D and Omega 3 Fatty Acid supplementation give as liquid drops and gel capsules that can be swallowed or added to food
  Interventions:

  • Biological: Autologous UCB
  • Dietary Supplement: Omega 3 FA
  • Dietary Supplement: Vitamin D
• No Intervention: Control
  Subjects randomized to be controls will continue to use intensive insulin therapy in order to compare c-peptide production at 1 year in those receiving combination therapy vs those who do not

Publications *

• Haller MJ, Viener HL, Wasserfall C, Brusko T, Atkinson MA, Schatz DA. Autologous umbilical cord blood infusion for type 1 diabetes. Exp Hematol. 2008 Jun;36(6):710-5. doi: 10.1016/j.exphem.2008.01.009. Epub 2008 Mar 20. Review.
• Haller MJ, Wasserfall CH, Hulme MA, Cintron M, Brusko TM, McGrail KM, Wingard JR, Theriaque DW, Shuster JJ, Ferguson RJ, Kozuch M, Clare-Salzler M, Atkinson MA, Schatz DA. Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes. Biol Blood Marrow Transplant. 2013 Jul;19(7):1126-9. doi: 10.1016/j.bbmt.2013.04.011. Epub 2013 Apr 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 1, 2009): 15
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• TID diagnosis confirmed by presence of at least 1 diabetes autoantibody Children ≥ 1 years
• Stored autologous umbilical cord blood (15 sought) in an AABB and/or FACT accredited cord bank.
• Stimulated C-peptide > 0.2pmol/L on MMTT
• Cord blood meets all selection and testing criteria (see below).
• Normal screening values for CBC, Renal function and electrolytes (BMP with Ca, Mg, and Phos).
• Willing to comply with intensive diabetes management

Exclusion Criteria:

• Complicating medical issues that would interfere with blood drawing or monitoring.
• Chronic use of steroids or other immunosuppressive agents for other conditions.
• Positive infectious disease markers from mother's blood or cord at time of -collection (See below for details).
• Any evidence of illness on planned infusion date (i.e. fever >38.5 C, vomiting, diarrhea, wheezing, or crackles).
• Allergy to DHA (Omega 3) or Vitamin D
• Hypercalcemia

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00873925
• Other Study ID Numbers: UF IRB 696-2008
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Florida
• Study Sponsor: University of Florida

Collaborators

• Juvenile Diabetes Research Foundation
• National Institutes of Health (NIH)

Investigators

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

• PRS Account: University of Florida
• Verification Date: April 2013