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Interferon-Alpha for Diabetes Mellitus Type 1

Primary Purpose

Insulin-Dependent Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
30,000 units hrINF-alpha
5,000 hrINF-alpha
Placebo
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insulin-Dependent Diabetes Mellitus focused on measuring Diabetes, Immunotherapy, Study Drug, Insulin Dependent Diabetes, Diabetes Mellitus, TIBM

Eligibility Criteria

3 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike
  • Children's Hospital - St. Paul
  • Children's Hospital - Kansas City
  • University of Texas, Dallas
  • University of Texas, Houston

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

5,000 Units hrIFN-alpha

30,000 hrIFN-alpha

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Serum glucose
Serum glucose or blood sugar measurements determine how much sugar is in the blood.
Hemoglobin A1C
a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

Full Information

First Posted
September 19, 2001
Last Updated
November 18, 2013
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00024518
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
September 2001 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin-Dependent Diabetes Mellitus
Keywords
Diabetes, Immunotherapy, Study Drug, Insulin Dependent Diabetes, Diabetes Mellitus, TIBM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
5,000 Units hrIFN-alpha
Arm Type
Experimental
Arm 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.
Arm Title
30,000 hrIFN-alpha
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
30,000 units hrINF-alpha
Other Intervention Name(s)
Human Recombinant Interferon-alpha
Intervention Type
Drug
Intervention Name(s)
5,000 hrINF-alpha
Other Intervention Name(s)
Human Recombinant Interferon-alpha
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
placebo was prepared as saline alone with 6mg human serum albumin (HSA).
Primary Outcome Measure Information:
Title
C-Peptide Level
Description
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.
Time Frame
Baseline - 3mth, 6mnth, 9mnth, 12mnth
Secondary Outcome Measure Information:
Title
Serum glucose
Description
Serum glucose or blood sugar measurements determine how much sugar is in the blood.
Time Frame
baseline - 3mths, 6mnths, 9mnths, 12mnths
Title
Hemoglobin A1C
Description
a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame
Baseline - 3mnths, 6mnths, 9mnths, 12mnths

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristina I Rother, M.D.
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Staley A Brod, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Children's Hospital - St. Paul
City
St. Paul
State/Province
Minnesota
Country
United States
Facility Name
Children's Hospital - Kansas City
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
University of Texas, Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
Facility Name
University of Texas, Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
7969282
Citation
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.
Results Reference
background
PubMed Identifier
3517648
Citation
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.
Results Reference
background
PubMed Identifier
9794112
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. doi: 10.1007/s001250051056.
Results Reference
background
PubMed Identifier
19564474
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;32(7):1250-5. doi: 10.2337/dc08-2029. Erratum In: Diabetes Care. 2009 Sep;32(9):1751.
Results Reference
result
Links:
URL
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2001-DK-0249.html
Description
NIH Clinical Center Detailed Web Page

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Interferon-Alpha for Diabetes Mellitus Type 1

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