Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

The purpose of this study is to determine if autologous nonmyeloablative hematopoietic stem cell transplantation is able to induce prolonged and significant increases of C-peptide levels associated with absence of or reduction of daily insulin.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Procedure: Autologous hematopoietic stem cell transplantation

Detailed Description

Patients with type 1 DM depend on exogenous insulin administration for survival and for control of long-term complications. The best-established treatment is tight control of blood glucose achieved by frequent daily injections or continuous subcutaneous infusion of insulin, ie, intensive insulin therapy. Although insulin therapy has developed enormously, even the most modern technologies do not allow the maintenance of normoglycemia.

Since the establishment of the autoimmune etiology of type 1 DM in the late 1970s, many clinical trials analyzing the effects of different types of immune interventions demonstrated that beta-cell preservation is an achievable target in different degrees.

Controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM.

This is a prospective pilot study which will enroll patients with type 1 diabetes mellitus within the first months of diagnosis, with clinical and laboratory findings. The donor stimulation will be with cyclophosphamide, filgrastim, and mesna. The cells will be recollected from peripheral blood by apheresis and refrigerated. The patients will receive a nonmyeloablative conditioning regimen with cyclophosphamide and fludarabine, and after this, the cells will be injected intravenously. They will receive a standard regimen of post-transplant prophylaxis. The duration of use of this prophylactic drugs scheme depends on the patient's recovery time. The reinfusion of stem cells will be completed after the last dose of cyclophosphamide, through a peripheral vein.

Lately, every three months, the C-Peptide levels, glucose and insulin serum levels will be measured.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly diagnosed in type 1 diabetes mellitus

Exclusion Criteria:

• Patients with HIV
• Patients with Hepatitis
• Patients with hematologic disease
• Patients with hearth failure
• Renal, Hepatic or psychiatric disease
• Pregnant patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hematopoietic stem cells

Procedure: Autologous hematopoietic stem cell transplantation; Patients will receive a stimulation with filgrastim 10mcg/Kg per day during 4 days and cyclophosphamide 1.5g/m2 per day during 2 days and mesna 300mg/m2 i.v. in 4 hours for prophylaxis (uroprotection). Lately, the stem cells will be recollected by apheresis. After that, the patients will receive a conditioning regimen with cyclophosphamide 500mg/m2 per day during 4 days and fludarabine 30mg/m2 per day during 4 days. After the last dose of cyclophosphamide, the autologous hematopoietic stem cell transplantation will be done on day 0, by peripheral vein. Then, a standard regimen of prophylaxis with oral ciprofloxacin 500mg every 12 hours, acyclovir 400mg every 8 hours, fluconazole 100mg per day and omeprazole 20mg per day for the recovery time of each patient.; Other Names: Stem cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-peptide levels before and after the hematopoietic stem cell transplantation	Every 3 months for 1 year.

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum levels of Hb A1C before and after the hematopoietic stem cell transplantation	Every month for 1 year.

Collaborators and Investigators

• Sponsor: Dra. Olga Graciela Cantu Rodriguez
• Investigators: Principal Investigator: Fernando J Lavalle, MD, Hospital Universitario Dr. Jose Eleuterio Gonzalez; Study Chair: David Gómez, MD, Hospital Universitario Dr. Jose Eleuterio Gonzalez; Study Director: Olga G Cantú, MD, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Publications and helpful links

General Publications

• Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Apr 15;301(15):1573-9. doi: 10.1001/jama.2009.470.
• Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med. 1998 Apr 1;128(7):517-23. doi: 10.7326/0003-4819-128-7-199804010-00001.
• Couri CE, Voltarelli JC. Potential role of stem cell therapy in type 1 diabetes mellitus. Arq Bras Endocrinol Metabol. 2008 Mar;52(2):407-15. doi: 10.1590/s0004-27302008000200029.
• Couri CE, Foss MC, Voltarelli JC. Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting beta-cell regeneration. Braz J Med Biol Res. 2006 Oct;39(10):1271-80. doi: 10.1590/s0100-879x2006001000002. Epub 2006 Aug 22.
• Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76. doi: 10.1001/jama.297.14.1568.
• Voltarelli JC, Couri CE. Stem cell transplantation for type 1 diabetes mellitus. Diabetol Metab Syndr. 2009 Sep 16;1(1):4. doi: 10.1186/1758-5996-1-4.
• Otonkoski T, Gao R, Lundin K. Stem cells in the treatment of diabetes. Ann Med. 2005;37(7):513-20. doi: 10.1080/07853890500300279.
• Cantu-Rodriguez OG, Lavalle-Gonzalez F, Herrera-Rojas MA, Jaime-Perez JC, Hawing-Zarate JA, Gutierrez-Aguirre CH, Mancias-Guerra C, Gonzalez-Llano O, Zapata-Garrido A, Villarreal-Perez JZ, Gomez-Almaguer D. Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant. J Clin Endocrinol Metab. 2016 May;101(5):2141-8. doi: 10.1210/jc.2015-2776. Epub 2016 Feb 9.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 11, 2010
• First Submitted That Met QC Criteria: May 11, 2010
• First Posted (Estimate): May 12, 2010

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 6, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: EN10-011