Interferon-Alpha for Diabetes Mellitus Type 1

Study Overview
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Brief Summary
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This study will see if interferon-alpha given early in the disease can stop or slow the immune attack on insulin-producing cells. In addition, the study will examine the safety and efficacy of interferon-alpha (given by mouth) to protect beta cell function. Patients between 3 and 25 years of age with Type 1 Diabetes Mellitus less then six weeks may be eligible for this study. All study-related tests and medications at the NIH Clinical Center are provided at no cost.

Detailed Description
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Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of the insulin-producing pancreatic beta-cells. The onset of clinical symptoms represents the endpoint of a chronic progressive decline in beta-cell function when the number of functional beta-cells descends below the critical mass required for maintenance of euglycemia ([1], [2]). However, the pancreas still retains the ability to produce a substantial amount of insulin. The goal of secondary prevention in T1DM is to avert further destruction of the remaining beta-cells and therefore delay or stop entry into the final stages of the disease associated with end organ damage. The rationale for this study is to interfere with the autoimmune beta-cell destruction early on in order to preserve as much residual endogenous insulin production as possible. We plan to administer oral interferon-alpha (IFN-a) on a daily basis, which has been shown to modify the clinical course of diabetes, to alter cytokine release, and reduce expression of T cell activation markers in an animal model ([3]) and a pilot project in humans (S. Brod, University of Texas, unpublished data). The one-year study is designed as a double blind randomized protocol using either 5,000 or 30,000 units of IFN-a versus placebo. Five centers will participate in this protocol (University of Texas Health Science Center in Houston; Dallas; Children's Hospital, St. Paul, MN; Kansas City and NIH, Bethesda, Maryland).

Official Title
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Ingested Interferon-Alpha: Prolongation or Permanence of the Honeymoon Phase in Newly Diagnosed Diabetes Mellitus

Conditions
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Insulin-Dependent Diabetes Mellitus

Intervention / Treatment
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* Drug: 30,000 units hrINF-alpha
* Drug: 5,000 hrINF-alpha
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: T1DM of less than 6 weeks duration in patients between 3 and 25 years of age. Besides T1DM, no concurrent illness. EXCLUSION CRITERIA: Treatment with immunosuppressive or immunostimulatory medications such as azathioprine, nicotinamide, superoxide dismutase-desferroxamine, aminoguanidine, oral insulin or other experimental therapies at the present time or in the past. Abnormal pre-treatment white blood cell count (WBC) or thrombocytopenia. Known active diseases, e.g. cardiac, renal, hepatic diseases or immunodeficiency. History of cancer, neuropathy seizure disorders (except typical history of febrile seizures in childhood), peripheral vascular disease, coagulation abnormalities, autoimmune disease (except type 1 diabetes) or cerebrovascular disease. Ongoing use of medications known to influence glucose tolerance (e.g. sulfonylureas, metformin, diphenylhydantoin, thiazide or other potassium depleting diuretics, beta-adrenergic blockers, niacin) except insulin. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial. Inability to give informed consent or assent. Participation in a clinical trial within the previous 6 weeks. Lactating or pregnant female individual (individuals will be advised not to volunteer for the protocol if they plan to become pregnant during the time of the study and they are instructed to use an effective method of contraception). Age above 25 years, since there may be several subtypes of T1DM.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo was prepared as saline alone with 6mg human serum albumin (HSA). Subjects orally ingested one vial each morning before breakfast with at least 150mL water. | Other: Placebo<br>* placebo was prepared as saline alone with 6mg human serum albumin (HSA).<br>|
| Experimental: 5,000 Units hrIFN-alpha<br>hrIFN-alpha = human recombinant interferon-alpha. 5,000 units was prepared along with saline and 6mg HSA. Subjects orally ingested one vial each morning before breakfast with at least 150mL water. | Drug: 5,000 hrINF-alpha<br> <br> * Other names: Human Recombinant Interferon-alpha;|
| Experimental: 30,000 hrIFN-alpha<br>30,000 units hrIFN-alpha was prepared along with saline and 6mg HSA. Subjects orally ingested one vial each morning before breakfast with at least 150mL water. | Drug: 30,000 units hrINF-alpha<br> <br> * Other names: Human Recombinant Interferon-alpha;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-Peptide Level | The Connecting Peptide, or C-peptide, is a short 31-amino-acid protein that connects insulin's A-chain to its B-chain in the proinsulin molecule. | Baseline - 3mth, 6mnth, 9mnth, 12mnth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum glucose | Serum glucose or blood sugar measurements determine how much sugar is in the blood. | baseline - 3mths, 6mnths, 9mnths, 12mnths | 
| Hemoglobin A1C | a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. | Baseline - 3mnths, 6mnths, 9mnths, 12mnths | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Immunotherapy, Study Drug, Insulin Dependent Diabetes, Diabetes Mellitus, TIBM