Effects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome

Obesity and the metabolic syndrome are considered as chronic low-grade inflammatory states. Elevated pro-inflammatory mediators in obesity and metabolic syndrome have an inhibitory effect on the hypothalamic-pituitary-gonadal axis (HPG axis) leading to hypogonadism. Decreased testosterone production in obese men in turn promotes additional fat deposition, contributing to a vicious cycle of fat accumulation. This complex pathophysiological interplay is termed hypogonadal-obesity-adipocytokine hypothesis, describing a bidirectional relationship between low levels of testosterone and the metabolic syndrome.

TestIL is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to test the hypothesis that inhibition of IL-1-activity diminishes the inhibitory effects on HPG axis and increases testosterone levels in men with metabolic syndrome.

Inclusion criteria

• Informed consent as documented by signature,
• Men at the age between 18 and 75 years,
• BMI >30 kg/m2 and at least 1 manifestation of the metabolic syndrome (i.e. prediabetes, diabetes, hypertension, dyslipidemia),
• Total testosterone level <12 nmol/l.

Exclusion criteria

• Previous or current medication with testosterone,
• Testosterone deficiency of other cause, i.e. primary hypogonadism caused e.g. by Klinefelters syndrome, cryptorchidism, condition following orchiectomy. Known secondary hypogonadism caused by pituitary adenoma. Patients on antiandrogen medication,
• Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months,
• Severe immunosuppression (e.g. patients with previously known infection with human immunodeficiency virus and a cluster of differentiation 4 (CD4) count below 350 x 109/L, patients on immunosuppressive therapy after solid organ transplantation and neutropenic patients with neutrophil count < 500 x 109/L and patients under chemotherapy with neutrophils 500-1000 x 109/L with an expected decrease to values < 500 x 109/L),
• Hematologic disease (leukocyte count < 1.5 x 109/l, hemoglobin < 11 g/dl, platelets <100 x 103/µl),
• Other clinically significant concomitant disease states (e.g., renal failure [Creatinine-Clearance < 30 ml/min], hepatic dysfunction [transaminases >3x upper normal range], active carcinoma,
• History of tuberculosis,
• Known or suspected non-compliance, drug or alcohol abuse,
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to anakinra/Kineret®,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Previous enrolment into the current study.