Effect of Anakinra on Insulin Sensitivity in Type 1 Diabetes Mellitus

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by Radboud University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT01285245
First received: November 26, 2010
Last updated: April 13, 2011
Last verified: November 2010
  Purpose

The purpose of this study is to test whether anakinra is able to reduce insulin resistance.

This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. By using this patient group, all positive effects on glycemic control should be the consequence of improved insulin sensitivity.


Condition Intervention Phase
Diabetes Mellitus
Drug: kineret
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Interleukin-1 Receptor Antagonist on Insulin Sensitivity in Type 1 Diabetes Mellitus.

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • insulin sensitivity as determined by euglycemic hyperinsulinemic clamp [ Time Frame: change in insulin sensitivity after 1 week of treatment with anakinra as compared to baseline ] [ Designated as safety issue: No ]
    insulin sensitivity measured by euglycemic hyperinsulinemic clamp


Secondary Outcome Measures:
  • glycemic control [ Time Frame: baseline, after 1 week of treatment and 4 weeks after treatment termination ] [ Designated as safety issue: No ]
    HbA1c, fasting glucose

  • adipocyte insulin sensitivity [ Time Frame: baseline, after 1 week of treatment, 4 weeks after treatment termination ] [ Designated as safety issue: No ]
  • circulating hormonal and inflammatory factors and lipid profile [ Time Frame: baseline, after 1 week of treatment, 4 weeks after treatment termination ] [ Designated as safety issue: No ]
  • insulin sensitivity as determined by euglycemic hyperinsulinemic clamp [ Time Frame: change in insulin sensitivity 4 weeks after stopping anakinra treatment as compared to baseline ] [ Designated as safety issue: No ]
    insulin sensitivity measured by euglycemic hyperinsulinemic clamp


Estimated Enrollment: 16
Study Start Date: April 2011
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: kineret Drug: kineret
once daily 100 mg of kineret subcutaneously for 8 days
Other Names:
  • anakinra
  • interleukin-1 receptor antagonist

Detailed Description:

Although typically associated with type 2 diabetes, insulin resistance has been documented in Type 1 diabetes. Insulin resistance may also play an important role in the pathophysiology of type 1 diabetes mellitus. Once diabetes has emerged chronically elevated glucose levels further induce insulin resistance (glucose toxicity).

Inflammation is an important link between obesity and insulin resistance. The mechanism of hyperglycemia-induced insulin resistance is not clear, but evidently must be related to high glucose levels. There are indications that chronic hyperglycemia can induce inflammation, for example hyperglycemia induces IL-1β release, and recent studies have shown an interaction with thioredoxin interacting protein (TXNIP), at the level of the beta-cell but also, as found by our own group, at the level of the adipose tissue

All together, these findings suggest that blocking IL-1β-receptor activation by the interleukin-1 receptor antagonist anakinra, may reverse insulin resistance associated both with obesity and/or chronic hyperglycemia. When applied in (hyperglycemic) subjects with type 2 diabetes, blocking IL-1β should diminish the effects of glucose toxicity both at the level of beta-cell function as at the level of insulin sensitivity. When applied in (hyperglycemic) subjects with type 1 diabetes, the effects of glucose toxicity at the level of insulin sensitivity should decrease.

In order to be able to study an isolated effect of IL-1β blockade on insulin sensitivity, this study will test this hypothesis in subjects with type 1 diabetes and hence provide a proof of principle in vivo in humans for a proposed link between hyperglycemia, inflammation and insulin resistance.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 1 diabetes for more than 5 years
  • Body mass index of > 25 kg/m2
  • Insulin requirement > 0.5 U/kg bodyweight
  • HbA1c>7.5%, stable glycemic control

Exclusion Criteria:

  • Inability to give informed consent
  • Presence of any medical condition that might interfere with the current study protocol.
  • Immunodeficiency or immunosuppressive treatment (including TNFα blocking agents and corticosteroids)
  • Anti-inflammatory drugs (including nonsteroidal anti-inflammatory drugs, 100 mg or less of aspirin per day is allowed)
  • Signs of current infection (fever, C-reactive protein (CRP) > 30 mmol/l, treatment with antibiotics, previous or current diagnosis of tuberculosis.
  • A history of recurrent infections
  • Pregnancy or breast-feeding (contraception of at least 3 months before inclusion is required for fertile women)
  • Liver disease (aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range)
  • Renal disease (creatinine > 130 µmol/l
  • Neutropenia < 2 x 109/l
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285245

Contacts
Contact: Edwin JP van Asseldonk, MD +31243619857 e.vanasseldonk@aig.umcn.nl

Locations
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Cees J Tack, MD PhD Radboud University
  More Information

No publications provided

Responsible Party: Edwin J.P. van Asseldonk, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT01285245     History of Changes
Other Study ID Numbers: NL34377.091.10, 2010-023479-24
Study First Received: November 26, 2010
Last Updated: April 13, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
insulin sensitivity
interleukin-1 receptor antagonist
inflammation
hyperglycemia-induced insulin resistance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hyperinsulinism
Insulin
Interleukin 1 Receptor Antagonist Protein
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014