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

Phase 1

• Conditions: Insulin Resistant Human Obesity

• Registration Number: EUCTR2005-000181-39-AT
• Lead Sponsor: Med. Universitaetsklinik Graz, ao Univ. Professor Dr. med. Thomas C. Wascher

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-07-27
• Last Update Posted: 31 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

Subjects to be included must meet the following criteria:

1. Men between 20 and 50 years of age.
2. BMI between and including 30 and 35 kg/m2
3. HOMA index > 2.5
4. History of stable weight (+/- 2 kg) > 3 months
5. Blood pressure > 135 / 85 mmHg (or treated hypertension)
6. Triglycerides > 1.7 mmol/l or HDL-cholesterol < 1.3 mmol/l
7. Men or their partner must use adequate birth control measures (eg, abstinence,
oral contraceptives, intrauterine device, barrier method with spermicide, or
surgical sterilization) for the duration of the study and should continue such
precautions for 6 months after receiving the last infusion.
8. The screening laboratory test results must meet the following criteria:
a. Hemoglobin>= 8.5 g/dL
b. WBC>= 3.5 x 10 hoch 9/L
c. Neutrophils>= 1.5 x 10 hoch 9/L
d. Platelets>= 100 x 10 hoch 9/L
e. SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper
limit of normal range for the laboratory conducting the test.

9. Subject must be able to adhere to the study visit schedule and other protocol
requirements.
10. The subject must be capable of giving informed consent and the consent must
be obtained prior to any screening procedures.
11. Must have a chest radiograph within 3 months prior to first infusion with no
evidence of malignancy, infection or fibrosis.
12. Are considered eligible according to the following tuberculosis (TB) screening
criteria:
a. Have no history of latent or active TB prior to screening.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had 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.
d. Within 1 month prior to the first administration of study agent, either have a
negative tuberculin skin test, as outlined in Appendix B, 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
e. Have a chest radiograph (both posterior-anterior and lateral views), taken
within 3 months prior to the first administration of study agent and read by a
qualified radiologist, with no evidence of current active TB or old inactive TB.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects will be excluded from this study for any of the following reasons:

1. Patients with overt diabetes (fasting glucose > 7.0 mmol/l).
2. Current treatment with angiotensin II antagonists or ACE inhibitors.
3. Treatment indication with statins according to the current NCEP III criteria.
4. Treatment indication with low dose acetylsalicylic acid according to the current
AHA quidelines or any other NSAID.
5. Current smokers.
6. Patients with (a history of) an autoimmune disease.
7. Use of any investigational drug within 1 month prior to screening or within 5 half-
lives of the investigational agent, whichever is longer.
8. Treatment with any other therapeutic agent targeted at reducing TNFa (eg,
pentoxifylline, thalidomide, etanercept, adalimumab) within 3 months of screening.
9. Previous administration of infliximab.
10. History of receiving human/murine recombinant products or known allergy to
murine products.
11. 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.
12. Documented HIV infection.
13. Active hepatitis- B or antibodies against hepatitis-C
14. Have a history of latent or active granulomatous infection, including TB,
histoplasmosis, or coccidioidomycosis, prior to screening.
15. Have or have had a opportunistic infection (eg, herpes zoster [shingles],
cytomegalovirus, Pneumocystis carinii, aspergillosis,) within 6 months prior to
screening.
16. 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).
17. Concomitant congestive heart failure, including medically controlled
asymptomatic patients.
18. Presence of a transplanted organ (with the exception of a corneal transplant > 3
months prior to screening).
19. Malignancy within the past 5 years (except for squamous or basal cell carcinoma
of the skin that has been treated with no evidence of recurrence).
20. History of lymphoproliferative disease including lymphoma, or sign and symptoms
suggestive of possible lymphoproliferative disease, such as lymphadenopathy of
unusual size or location (such as nodes in the posterior triangle of the neck,
infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
21. Known recent substance abuse (drug or alcohol).
22. Poor tolerability of venipuncture or lack of adequate venous access for required
blood sampling during the study period.
23. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of
screening.
24. 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified