Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus - Full Text View

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Procedure: Autologous hematopoietic stem cell transplantation	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Resource links provided by NLM:

Genetics Home Reference related topics: type 1 diabetes

MedlinePlus related topics: Diabetes Diabetes Type 1

U.S. FDA Resources

Further study details as provided by Hospital Universitario Dr. Jose E. Gonzalez:

Primary Outcome Measures:

C-peptide levels before and after the hematopoietic stem cell transplantation [ Time Frame: Every 3 months for 1 year. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Serum levels of Hb A1C before and after the hematopoietic stem cell transplantation [ Time Frame: Every month for 1 year. ] [ Designated as safety issue: Yes ]


Enrollment:	15
Study Start Date:	May 2010
Study Completion Date:	December 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Stem cell therapy

Arms

Assigned Interventions

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 Name: Stem cell therapy

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


Ages Eligible for Study:	2 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01121029

Locations


Mexico
Hospital Universitario Dr. José Eleuterio González
Monterrey, Nuevo Leon, Mexico, 64460

Sponsors and Collaborators

Dra. Olga Graciela Cantu Rodriguez

Investigators


Principal Investigator:	Fernando J Lavalle, MD	Hospital Universitario Dr. José Eleuterio González
Study Chair:	David Gómez, MD	Hospital Universitario Dr. José Eleuterio González
Study Director:	Olga G Cantú, MD	Hospital Universitario Dr. José Eleuterio González

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

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

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.

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.

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.

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.

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.

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.


Responsible Party:	Dra. Olga Graciela Cantu Rodriguez, Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus, Hospital Universitario Dr. Jose E. Gonzalez
ClinicalTrials.gov Identifier:	NCT01121029 History of Changes
Other Study ID Numbers:	EN10-011
Study First Received:	May 11, 2010
Last Updated:	December 6, 2012
Health Authority:	Mexico: Ethics Committee

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 1 Autoimmune Diseases Endocrine System Diseases	Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases

ClinicalTrials.gov processed this record on February 25, 2015