Interferon-Alpha for Diabetes Mellitus Type 1

• ClinicalTrials.gov Identifier: NCT00024518
• Recruitment Status: Completed
• First Posted: September 19, 2001
• Last Update Posted: November 19, 2013
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: September 19, 2001
• First Posted Date: September 19, 2001
• Last Update Posted Date: November 19, 2013
• Study Start Date: September 2001
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2013)

C-Peptide Level [ Time Frame: Baseline - 3mth, 6mnth, 9mnth, 12mnth ]

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.

• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00024518 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 18, 2013)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Interferon-Alpha for Diabetes Mellitus Type 1
• Official Title: Ingested Interferon-Alpha: Prolongation or Permanence of the "Honeymoon" Phase in Newly Diagnosed Diabetes Mellitus
• Brief 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.

Detailed 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).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Insulin-Dependent Diabetes Mellitus

Intervention

• Drug: 30,000 units hrINF-alpha
  Other Name: Human Recombinant Interferon-alpha
• Drug: 5,000 hrINF-alpha
  Other Name: Human Recombinant Interferon-alpha
• Other: Placebo
  placebo was prepared as saline alone with 6mg human serum albumin (HSA).

Study Arms

• Placebo Comparator: 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.
  Intervention: Other: Placebo
• Experimental: 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.
  Intervention: Drug: 5,000 hrINF-alpha
• Experimental: 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.
  Intervention: Drug: 30,000 units hrINF-alpha

Publications *

• Atkinson MA, Maclaren NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med. 1994 Nov 24;331(21):1428-36. Review.
• Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986 May 22;314(21):1360-8. Review.
• 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.
• 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. Erratum in: Diabetes Care. 2009 Sep;32(9):1751.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 25, 2009): 57
• Original Enrollment (submitted: June 23, 2005): 120
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00024518
• Other Study ID Numbers: 010249; 01-DK-0249
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: The University of Texas Health Science Center, Houston
• Study Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Kristina I Rother, M.D.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Principal Investigator: Staley A Brod, MD; The University of Texas Health Science Center, Houston

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: November 2013