Interferon-Alpha for Diabetes Mellitus Type 1

Insulin-Dependent Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00024518
• Other study ID #: 010249
• Secondary ID: 01-DK-0249
• Status: Completed
• Phase: Phase 2
• First received: September 19, 2001
• Last updated: November 18, 2013
• Start date: September 2001
• Est. completion date: September 2008

Study information

• Verified date: November 2013
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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of T cell activation markers in an animal model ([3]) and a pilot project in humans (S. Brod, University of Texas, unpublished data).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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 25 Years

Eligibility

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Insulin-Dependent Diabetes Mellitus

Intervention

Drug:
• 30,000 units hrINF-alpha

• 5,000 hrINF-alpha

Other:
• Placebo
placebo was prepared as saline alone with 6mg human serum albumin (HSA).

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	University of Texas, Dallas	Dallas	Texas
United States	University of Texas, Houston	Houston	Texas
United States	Children's Hospital - Kansas City	Kansas City	Missouri
United States	Children's Hospital - St. Paul	St. Paul	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med. 1994 Nov 24;331(21):1428-36. Review. — View Citation

Brod SA, Malone M, Darcan S, Papolla M, Nelson L. Ingested interferon alpha suppresses type I diabetes in non-obese diabetic mice. Diabetologia. 1998 Oct;41(10):1227-32. — View Citation

Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986 May 22;314(21):1360-8. Review. — View Citation

Rother KI, Brown RJ, Morales MM, Wright E, Duan Z, Campbell C, Hardin DS, Popovic J, McEvoy RC, Harlan DM, Orlander PR, Brod SA. Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes. Diabetes Care. 2009 Jul; — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Serum glucose	Serum glucose or blood sugar measurements determine how much sugar is in the blood.	baseline - 3mths, 6mnths, 9mnths, 12mnths	No
Secondary	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	No

External Links

•   NIH Clinical Center Detailed Web Page