Interferon-Alpha for Diabetes Mellitus Type 1

NCT ID: NCT00024518

Last Updated: 2013-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-09-30

Study Completion Date

2008-09-30

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of T cell activation markers in an animal model (\[3\]) and a pilot project in humans (S. Brod, University of Texas, unpublished data).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

Conditions

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Insulin-Dependent Diabetes Mellitus

Keywords

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Diabetes Immunotherapy Study Drug Insulin Dependent Diabetes Diabetes Mellitus TIBM

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

5,000 Units hrIFN-alpha

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.

Group Type EXPERIMENTAL

5,000 hrINF-alpha

Intervention Type DRUG

30,000 hrIFN-alpha

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.

Group Type EXPERIMENTAL

30,000 units hrINF-alpha

Intervention Type DRUG

Interventions

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30,000 units hrINF-alpha

Intervention Type DRUG

5,000 hrINF-alpha

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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Human Recombinant Interferon-alpha Human Recombinant Interferon-alpha

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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kristina I Rother, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Staley A Brod, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

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National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Children's Hospital - St. Paul

Saint Paul, Minnesota, United States

Site Status

Children's Hospital - Kansas City

Kansas City, Missouri, United States

Site Status

University of Texas, Dallas

Dallas, Texas, United States

Site Status

University of Texas, Houston

Houston, Texas, United States

Site Status

Countries

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United States

References

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Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med. 1994 Nov 24;331(21):1428-36. doi: 10.1056/NEJM199411243312107. No abstract available.

Reference Type BACKGROUND
PMID: 7969282 (View on PubMed)

Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986 May 22;314(21):1360-8. doi: 10.1056/NEJM198605223142106. No abstract available.

Reference Type BACKGROUND
PMID: 3517648 (View on PubMed)

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. doi: 10.1007/s001250051056.

Reference Type BACKGROUND
PMID: 9794112 (View on PubMed)

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;32(7):1250-5. doi: 10.2337/dc08-2029.

Reference Type RESULT
PMID: 19564474 (View on PubMed)

Related Links

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Other Identifiers

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01-DK-0249

Identifier Type: -

Identifier Source: secondary_id

010249

Identifier Type: -

Identifier Source: org_study_id