|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|Insulin Resistant Human Obesity
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|The objectives of the study are to test whether neutralizing TNF-α with infliximab affects insulin resistance and phenotypical manifestations of the metabolic syndrome such as:
- Fasting plasma insulin
- Iv-GTT derived parameters of insulin resistance and β-cell function
- Total body fat
- Plasma lipid profile
- Vascular endothelial dysfunction
- Circulating markers of inflammation and endothelial dysfunction
|E.2.2||Secondary objectives of the trial ||
|E.2.3||Trial contains a sub-study || Information not present in EudraCT
|E.3||Principal 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
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
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
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.
|E.4||Principal 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 TNFα (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
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
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
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
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.
|E.5 End points
|E.5.1||Primary end point(s)||
|The primary endpoint in this study is the change in fasting insulin levels between base line levels (day 0) and day 70.
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| No
|E.6.10||Pharmacogenetic|| Information not present in EudraCT
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| No
|E.7.1.1||First administration to humans|| No
|E.7.1.2||Bioequivalence study|| No
|E.184.108.40.206||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| No
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| Yes
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || Yes
|E.8.1.5||Parallel group|| No
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
The trial involves single site in the Member State concerned
|E.8.4|| The trial involves multiple sites in the Member State concerned || No
|E.8.5||The trial involves multiple Member States|| No
|E.8.6 Trial involving sites outside the EEA
|E.8.6.1||Trial being conducted both within and outside the EEA|| No
|E.8.6.2||Trial being conducted completely outside of the EEA|| Information not present in EudraCT
|E.8.7||Trial has a data monitoring committee|| Information not present in EudraCT
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|End of trial is defined as a patient completing the last scheduled visit.
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||1
|E.8.9.1||In the Member State concerned months||6
|E.8.9.1||In the Member State concerned days||
|E.8.9.2||In all countries concerned by the trial years||1
|E.8.9.2||In all countries concerned by the trial months||6