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

NCT00636142 | Completed Phase 4 DMC

• 1 other identifier: 2005-000181-39
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Insulin Resistance; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in fasting insulin levels

  70 days

Secondary Outcomes (1)

• Blood pressure; Vascular reactivity; Blood measurements + calculation of the HOMA; Iv-GTT; Body fat mass (DEXA); Safety;

  70 days

Study Arms (2)

1

ACTIVE COMPARATOR

Infliximab

Biological: Infliximab

2

PLACEBO COMPARATOR

Placebo

Biological: Infliximab

Interventions

Infliximab BIOLOGICAL

5 mg/kg body weight, maximal dose 500 mg; intravenous administration

Also known as: Remicade, EU/1/99/116/001-003

1; 2

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Department of Internal Medicine, Medical University of Graz

Graz, 8036, Austria

Location

Related Publications (1)

• Wascher TC, Lindeman JH, Sourij H, Kooistra T, Pacini G, Roden M. Chronic TNF-alpha neutralization does not improve insulin resistance or endothelial function in "healthy" men with metabolic syndrome. Mol Med. 2011 Mar-Apr;17(3-4):189-93. doi: 10.2119/molmed.2010.00221. Epub 2010 Nov 16.

  PMID: 21103669 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance; Metabolic Syndrome

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Thomas C. Wascher, MD

  Medical University of Graz, Graz, Austria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 11, 2008
• First Posted: March 14, 2008
• Study Start: September 1, 2005
• Primary Completion: June 1, 2007
• Study Completion: September 1, 2007
• Last Updated: March 14, 2008

Record last verified: 2008-03

Locations

AU (1)