Clinical trial NCT01121029: Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus
Official title: Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2010-05-12
Enrollment: 15
Sex: ALL
Minimum age (years): 2
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: C-peptide levels before and after the hematopoietic stem cell transplantation
timeFrame: Every 3 months for 1 year.
Secondary outcomes:
measure: Serum levels of Hb A1C before and after the hematopoietic stem cell transplantation
timeFrame: Every month for 1 year.
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González
state: Nuevo Leon
Study officials:
affiliation: Hospital Universitario Dr. José Eleuterio González
name: Fernando J Lavalle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Dr. José Eleuterio González
name: David Gómez, MD
role: STUDY_CHAIR
affiliation: Hospital Universitario Dr. José Eleuterio González
name: Olga G Cantú, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Otonkoski T, Gao R, Lundin K. Stem cells in the treatment of diabetes. Ann Med. 2005;37(7):513-20. doi: 10.1080/07853890500300279.
citation: 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.