Interferon-Alpha for Diabetes Mellitus Type 1

The University of Texas System (UT)

Status and phase: Completed; Phase 2

Conditions: Insulin-Dependent Diabetes Mellitus

Treatments: Drug: 5,000 hrINF-alpha; Drug: 30,000 units hrINF-alpha; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00024518

010249

01-DK-0249

Details and patient eligibility

About

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.

Full description

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of T cell activation markers in an animal model ([3]) and a pilot project in humans (S. Brod, University of Texas, unpublished data).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).

Enrollment: 57 patients

Sex: All

Ages: 3 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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57 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo

5,000 Units hrIFN-alpha

Experimental group

Description:

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.

Treatment:

Drug: 5,000 hrINF-alpha

30,000 hrIFN-alpha

Experimental group

Description:

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.

Treatment:

Drug: 30,000 units hrINF-alpha