We hypothesize that ingested human recombinant interferon-alpha (hrIFN-a) will prolong the
"honeymoon" period and enhance B cell survival in type 1 diabetes in a phase II randomized,
placebo-controlled, double-blind clinical trial. We have demonstrated that ingested IFN-a
prevents type 1 diabetes in the NOD mouse, prolongs the "honeymoon" period in newly
diagnosed type 1 diabetics, and delays murine islet allograft rejection. The natural history
of type 1 diabetes is unique for a phase frequently referred as the "honeymoon," a period in
which the insulin need becomes minimal and glycemic control improves. The B cell (the
insulin producing cell) partially recovers. However, as with all honeymoons, they end and
the patient becomes completely insulin-deficient. The general consensus of the
international diabetes community is to test potential preventive therapies for type 1
diabetes in newly diagnosed patients. Prolongation of the honeymoon as the reversal of the
disease is considered a positive result.
In this phase II randomized, double-blind, parallel-design clinical trial we will determine
whether ingested (oral) human recombinant IFN-a will prolong the "honeymoon" period and
increase counterregulatory anti-inflammatory cytokine(s).
We will determine the safety and efficacy of 30,000 units ingested hrIFN-a vs placebo in
eighty patients with newly diagnosed type 1 diabetes in a phase II trial for one year.
Primary outcome measures will be a 30% increase in C-peptide levels released after Sustacal
stimulation at 3, 6, 9, and 12 months after entry. Secondary outcome will be decreasing
titers of islet cell antibodies (ICA). If successful, a larger and longer phase III trial
of prevention of type 1 diabetes in high risk patients will be undertaken. We will also
determine if ingested hrIFN-a increases IL-4, IL-10 or IFN-a production in peripheral blood
mononuclear cells (PMNC) from patients with recent onset type 1 diabetes.
- Newly diagnosed type 1 diabetes (within one month of diagnosis).
- IDDM patients: Prepubescent, adolescent, or early adult patients.
- Patients below the age of 3 or over 25.
- Patients will not be eligible if they are on immunosuppressive or immunostimulatory
medications such as azathioprine, oral nicotinamide, superoxide
dismutase-desferroxamine, vitamin E, aminoguanidine, oral insulin or other
experimental therapies at any time.
- Patients with a history of alcoholism, renal, cardiac, or pulmonary disease or in
whom intellectual functioning is impaired sufficiently to interfere with the
understanding of the protocol, or participation in the treatment and evaluation
- Patients who are pregnant or nursing, or those who are not willing to practice an
acceptable birth control method
- Patients with abnormal pre-treatment values on WBC or who are receiving potentially