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

This study has been completed.
Sponsor:
Information provided by:
Medical University of Graz
ClinicalTrials.gov Identifier:
NCT00636142
First received: March 11, 2008
Last updated: March 13, 2008
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Obesity
Insulin Resistance
Metabolic Syndrome
Biological: Infliximab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • Change in fasting insulin levels [ Time Frame: 70 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Blood pressure; Vascular reactivity; Blood measurements + calculation of the HOMA; Iv-GTT; Body fat mass (DEXA); Safety; [ Time Frame: 70 days ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: September 2005
Study Completion Date: September 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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
  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00636142

Locations
Austria
Department of Internal Medicine, Medical University of Graz
Graz, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
Investigators
Principal Investigator: Thomas C. Wascher, MD Medical University of Graz, Graz, Austria
  More Information

No publications provided by Medical University of Graz

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas C. Wascher, MD, Department of Internal Medicine, Medical University of Graz
ClinicalTrials.gov Identifier: NCT00636142     History of Changes
Other Study ID Numbers: 2005-000181-39
Study First Received: March 11, 2008
Last Updated: March 13, 2008
Health Authority: Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Obesity
Metabolic Syndrome X
Insulin Resistance
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014