Hematopoietic Stem Cell Support Versus Insulin in T1D

NCT01285934 | Withdrawn Phase 1 DMC

• 1 other identifier: Diabetes2008
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• C-peptide

  C-peptide (fasting and every 30 minutes during 2 hour mixed meal tolerance test

  Every 6 months for 5 years

Secondary Outcomes (3)

• Insulin dose

  5 years

• Serum levels of hemoglobin A1c

  5 years

• Stimulated C-peptide levels during mixed meal tolerance test

  5 years

Study Arms (2)

Hematopoietic Stem Cell Transplantation

EXPERIMENTAL

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

control arm of intensive insulin therapy

OTHER

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

Interventions

Autologous Hematopoietic Stem Cell Transplantation BIOLOGICAL

All participants randomized to the transplant arm wil undergo Autologous Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

intensive insulin therapy DRUG

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.

Also known as: IIT

control arm of intensive insulin therapy

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• University of Sao Paulo General Hospital: collaborator

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 27, 2011
• First Posted: January 28, 2011
• Study Start: January 1, 2009
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 21, 2015

Record last verified: 2015-03