Hematopoietic Stem Cell Support Versus Insulin in T1D

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Collaborator:
University of Sao Paulo General Hospital
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT01285934
First received: January 27, 2011
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Type 1 diabetes mellitus (T1D) results from immune-mediated destruction of insulin-producing islet cells. The loss of islet cells is traditionally treated with insulin therapy and in some cases pancreas or islet cell transplantation. Another approach would be to preserve islet cell mass before it is irreversibly lost. Previous trials using immune suppression within 6 weeks of T1D onset have demonstrated diminished exogenous insulin requirements compared to untreated controls. In our prior phase I non-randomized study, by extending immune suppression to the point of immune ablation / immune reset with autologous HSC support, several patients with new onset T1D have maintained an insulin-free, drug free remissions for more than 4 years. Although these results appear highly promising, it may be argued that our results are mitigated by the documented honeymoon effect following T1D, that is by a normal transient insulin free interval occurring after disease onset in some patients. The goal of this trial is to extend this phase I study of new onset T1D to clarify whether our post transplant insulin free interval is due to treatment intervention (transplant) or a result of a normally occurring "insulin free honeymoon period". Both groups will receive identical change of life style (i.e. diet, exercise) education.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Biological: Autologous Hematopoietic Stem Cell Transplantation
Drug: intensive insulin therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of High Dose Immunosuppression and Autologous Hematopoietic Stem Cell Support Versus Intensive Insulin Therapy in Adults With Early Onset Type I Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • C-peptide [ Time Frame: Every 6 months for 5 years ] [ Designated as safety issue: Yes ]
    C-peptide (fasting and every 30 minutes during 2 hour mixed meal tolerance test


Secondary Outcome Measures:
  • Insulin dose [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Insulin dose, recorded as daily insulin dose in IU/Kg/day

  • Serum levels of hemoglobin A1c [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Stimulated C-peptide levels during mixed meal tolerance test [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: January 2009
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hematopoietic Stem Cell Transplantation
Patients who meet eligibility and have completed pre-HSCT testing in section 7.0 (study parameters) may be enrolled in the transplant arm and will undergo an Autologous Hematopoietic Stem Cell Transplantation
Biological: Autologous Hematopoietic Stem Cell Transplantation
All participants randomized to the transplant arm wil undergo Autologous Hematopoietic Stem Cell Transplantation
control arm of intensive insulin therapy
The control arm of intensive insulin therapy (IIT) will enroll all patients who meet eligibility but decline HSCT or whose insurance does not approve payment for HSCT before expiration of eligibility (within 5 months of disease onset)
Drug: intensive insulin therapy
The control arm will be either CSII via an insulin pump or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin.
Other Name: IIT

Detailed Description:

Eligible patients will have type 1 diabetes (aged ≥ 18 years old) within five months of disease diagnosis, and a positive antibody to an islet cell autoantigen, and fasting C-peptide > 0.2 nmol/l. Hematopoietic stem cells will be mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (10 g/kg/day) collected from peripheral blood by leukoapheresis and cryopreserved. HSC will injected IV after conditioning with cyclophosphamide (200 mg/kg) divided 50 mg/kg on day -5, -4, -3, -2, and rabbit antithymocyte globulin (4.5 mg/kg) divided 0.5 mg/kg day-5, and 1.0 mg/kg day -4, -3-, -2, -1. Rituxan (500mg) IV will be given on days -6 and +1. The control arm will receive either continuous subcutaneous insulin infusion (CSII) or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin. The main outcome measure will be: fasting C-peptide. Other outcome measures will include: daily exogenous insulin requirements, serum levels of hemoglobin A1c, area under the curve (AUC) C-peptide levels during mixed meal tolerance test, islet cell autoantigen antibody titers, and quality of life (QOL) short form 36 (SF-36) questionnaire.

  Eligibility

Ages Eligible for Study:   16 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 16 to 35 years old
  • A diagnosis of type 1 diabetes by hyperglycemia and at least 1 antibody to islet cell autoantigen: GAD, IAA, ICA, IA-2, or Slc30A8
  • Fasting C-peptide > 0.20 nmol / liter
  • Enrollment within 5 months of T1D diagnosis
  • Eligible patients must be referred to a fertility / reproductive endocrinologist and have written documentation of medical counseling advising patients about the risk of infertility and the possible options of sperm and oocyte banking before enrollment.

Exclusion Criteria:

  • HIV positive
  • Patients in the honeymoon phase not taking insulin
  • Hepatitis A, B, or C positive
  • On corticosteroids or other immune suppressive medications
  • History of diabetic ketoacidosis
  • Ongoing malignancy except localized treated basal cell or squamous skin cancer.
  • History of cardiac disease or congestive heart failure or ventricular tachycardia or abnormal dobutamine cardiac echocardiogram
  • Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a potential side effect of therapy.
  • Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  • DLCO < 60% of predicted
  • Resting LVEF < 45%
  • Creatinine > 1.5 mg/dl
  • Known hypersensitivity to E Coli derived proteins.
  • Transaminases greater than 2 times normal
  • Positive tuberculosis skin test
  • Any active infection
  • Any co-morbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate the study.
  • Failure to collect at least 2.0 x 106 CD34+ cells/kg
  • History of alcohol or illicit drug abuse
  • Unwilling to be compliant with change in life-style—diet and exercise
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285934

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sub-Investigator: Anthony Pick, MD         
Sponsors and Collaborators
Northwestern University
University of Sao Paulo General Hospital
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01285934     History of Changes
Other Study ID Numbers: Diabetes2008
Study First Received: January 27, 2011
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014