Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01121029
• Other study ID #: EN10-011
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 11, 2010
• Last updated: December 6, 2012
• Start date: May 2010
• Est. completion date: December 2012

Study information

• Verified date: December 2012
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 35 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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.

Locations

Country	Name	City	State
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Dra. Olga Graciela Cantu Rodriguez

Country where clinical trial is conducted

Mexico, 

References & Publications (7)

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. Epub 2006 Aug 22. Review. — View Citation

Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simões 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. — View 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. Review. — View 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. — View Citation

Otonkoski T, Gao R, Lundin K. Stem cells in the treatment of diabetes. Ann Med. 2005;37(7):513-20. Review. — View Citation

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simões 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C-peptide levels before and after the hematopoietic stem cell transplantation		Every 3 months for 1 year.	Yes
Secondary	Serum levels of Hb A1C before and after the hematopoietic stem cell transplantation		Every month for 1 year.	Yes

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