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
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 April 17, 2014