Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity

March 13, 2008 updated by: Medical University of Graz

A Prospective Trial of Anti-TNF-Alpha Chimeric Monoclonal Antibody (Infliximab, Remicade®) on Insulin Sensitivity, Beta Cell Function and Cardiovascular Risk Profile in Insulin Resistant Human Obesity

The aim of the study is to test whether neutralizing TNF-alpha with infliximab affects insulin resistance and phenotypical manifestations of the metabolic syndrome as fasting plasma insulin, total body fat, plasma lipid profile or vascular endothelial function in obese male subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Overweight and obesity are rapidly becoming one of the most pressing health problems. Obese subjects face an increased risk for cardiovascular events that is closely related to a cluster of metabolic disturbances (i.e. insulin resistance, hypertension, dyslipidemia and impaired fibrinolysis), collectively referred to as syndrome X. The actual mechanism underlying development of syndrome X has not been elucidated. Increased TNF-alpha activity has been proposed as a key factor.

The objectives of the study are to test whether neutralizing TNF-alpha with infliximab in obese subjects affects insulin resistance and phenotypical manifestations of the metabolic syndrome such as:

  • fasting plasma insulin
  • ivGTT derived parameters of insulin resistance and beta-cell function
  • total body fat
  • plasma lipid profile
  • vascular endothelial dysfunction

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Department of Internal Medicine, Medical University of Graz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Men, 20-50 years
  • BMI 30-35 kg/m2
  • HOMA index > 2.5
  • stable weight (+/- 2 kg) > 3 months
  • Blood pressure>135/85 mmHg (or treated hypertension)
  • Triglycerides>1.7 mmol/l or HDL-cholesterol<1.3 mmol/l

Adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.

Hemoglobin >= 8.5 g/dL WBC >= 3.5 x 109/L Neutrophils >= 1.5 x 109/L Platelets >= 100 x 109/L SGOT (AST) and AP <3xULN

Chest radiograph within 3 months prior to first infusion with no evidence of malignancy, infection or fibrosis.

No history of latent or active TB prior to screening. No signs or symptoms suggestive of active TB upon medical history and/or physical examination.

No recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.

Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test or have a newly identified positive tuberculin skin test during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent Have a chest radiograph taken within 3 months prior to the first administration of study agent with no evidence of current active TB or old inactive TB.

Exclusion Criteria:

  • Overt Diabetes mellitus
  • Current treatment with angiotensin II antagonists or ACE inhibitors.
  • Treatment indication with statins according to the current NCEP III criteria.
  • Treatment indication with low dose acetylsalicylic acid according to the current AHA guidelines or any other NSAID.
  • Current smokers.
  • Patients with (a history of) an autoimmune disease.
  • Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
  • Treatment with any other therapeutic agent targeted at reducing TNFα within 3 months of screening.
  • Previous administration of infliximab.
  • History of receiving human/murine recombinant products or known allergy to murine products.
  • Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
  • Documented HIV infection.
  • Active hepatitis- B or antibodies against hepatitis-C
  • History of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
  • Have or have had a opportunistic infection within 6 months prior to screening.
  • Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis).
  • Concomitant congestive heart failure, including medically controlled asymptomatic patients.
  • Presence of a transplanted organ
  • Malignancy within the past 5 years.
  • History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location or splenomegaly.
  • Known recent substance abuse (drug or alcohol).
  • Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
  • Have a chest radiograph within 3 months prior to randomization that shows an abnormality suggestive of a malignancy or current active infection, including TB.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Biological: Infliximab
5 mg/kg body weight, maximal dose 500 mg; intravenous administration
Other Names:
  • Remicade
  • EU/1/99/116/001-003
Active Comparator: 1
Infliximab
Biological: Infliximab
5 mg/kg body weight, maximal dose 500 mg; intravenous administration
Other Names:
  • Remicade
  • EU/1/99/116/001-003

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in fasting insulin levels
Time Frame: 70 days
70 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Blood pressure; Vascular reactivity; Blood measurements + calculation of the HOMA; Iv-GTT; Body fat mass (DEXA); Safety;
Time Frame: 70 days
70 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Graz

Investigators

  • Principal Investigator: Thomas C. Wascher, MD, Medical University of Graz, Graz, Austria

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

September 1, 2007

Study Registration Dates

First Submitted

March 11, 2008

First Submitted That Met QC Criteria

March 13, 2008

First Posted (Estimate)

March 14, 2008

Study Record Updates

Last Update Posted (Estimate)

March 14, 2008

Last Update Submitted That Met QC Criteria

March 13, 2008

Last Verified

March 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-000181-39

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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