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

Obesity Clinical Trial

— TestIL  

Official title:

Effects of IL-1 Beta on the Hypothalamic-pituitary-gonadal (HPG) Axis in Men With Obesity and Metabolic Syndrome - The TestIL Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02672592
• Other study ID #: EKNZ 2015-376
• Status: Completed
• Phase: Phase 3
• First received: January 22, 2016
• Last updated: July 10, 2017
• Start date: January 2016
• Est. completion date: June 2017

Study information

• Verified date: July 2017
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obesity and the metabolic syndrome in men are associated with a high prevalence of hypogonadism of up to 50%. Increased fat mass leads to augmented release of adipocytokines and pro-inflammatory cytokines such as IL-1-beta, IL-6 and tumor necrosis factor-alpha which in turn suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to hypogonadism. This pathophysiological interplay is termed hypogonadal-obesity-adipocytokine hypothesis. 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Informed consent as documented by signature,

2. Men at the age between 18 and 75 years,

3. BMI >30 kg/m2 and at least 1 manifestation of the metabolic syndrome (i.e. prediabetes, diabetes, hypertension, dyslipidemia),

4. Total testosterone level <12 nmol/l.

Exclusion Criteria:

1. Previous or current medication with testosterone,

2. 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,

3. Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months,

4. 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),

5. Hematologic disease (leukocyte count < 1.5 x 109/l, hemoglobin < 11 g/dl, platelets <100 x 103/µl),

6. Other clinically significant concomitant disease states (e.g., renal failure [Creatinine-Clearance < 30 ml/min], hepatic dysfunction [transaminases >3x upper normal range], active carcinoma,

7. History of tuberculosis,

8. Known or suspected non-compliance, drug or alcohol abuse,

9. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to anakinra/Kineret®,

10. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,

11. Previous enrolment into the current study.

Related Conditions & MeSH terms

• Hypogonadism
• Metabolic Syndrome X
• Obesity
• Syndrome

Intervention

Drug:
• Anakinra
Anakinra 100mg s.c. bid
• Sodium Chloride 0.9%
Sodium Chloride 0.9% s.c. bid

Locations

Country	Name	City	State
Switzerland	University Department of Medicine, Kantonsspital Aarau	Aarau
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total morning testosterone (nmol/l)		4 weeks
Secondary	Total morning testosterone (nmol/l)		1 week and 3 months
Secondary	Free testosterone (nmol/l)	Assessed by equilibrium dialysis	1 week, 4 weeks and 3 months
Secondary	Bioavailable testosterone (nmol/l)	Assessed by equilibrium dialysis	1 week, 4 weeks and 3 months
Secondary	Erectile dysfunction as assessed by International Index of Erectile Function (IIEF) score		1 week, 4 weeks and 3 months
Secondary	Clinical severity of hypogonadism as assessed by quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire		1 week, 4 weeks and 3 months
Secondary	Proportion of muscle mass as assessed by bioelectrical impedance Analysis		1 week, 4 weeks and 3 months
Secondary	Proportion of fat mass as assessed by bioelectrical impedance Analysis		1 week, 4 weeks and 3 months
Secondary	HbA1c (%)		1 week, 4 weeks and 3 months
Secondary	LH and FSH (IU/l)		1 week, 4 weeks and 3 months
Secondary	Inhibin B, ACTH (pg/ml)		1 week, 4 weeks and 3 months
Secondary	Prolactin, TSH, Insulin (mIU/l)		1 week, 4 weeks and 3 months
Secondary	Interleukin-1, Interleukin-6 (pg/ml)		1 week, 4 weeks and 3 months
Secondary	Cortisol basal (nmol/l)		1 week, 4 weeks and 3 months
Secondary	C-reactive protein (mg/l)		1 week, 4 weeks and 3 months
Secondary	free T4 (pmol/l)		1 week, 4 weeks and 3 months
Secondary	T3 (nmol/l)		1 week, 4 weeks and 3 months
Secondary	IGF-1 (nmol/l)		1 week, 4 weeks and 3 months
Secondary	GH (mU/l)		1 week, 4 weeks and 3 months
Secondary	Androstendione (µg/l)		1 week, 4 weeks and 3 months
Secondary	DHEAS (µmol/l)		1 week, 4 weeks and 3 months
Secondary	Oestradiol (pmol/l)		1 week, 4 weeks and 3 months
Secondary	Oestron (ng/l)		1 week, 4 weeks and 3 months
Secondary	17-OH-progesterone (nmol/l)		1 week, 4 weeks and 3 months
Secondary	Copeptin (pmol/l)		1 week, 4 weeks and 3 months
Secondary	Sex hormone-binding globulin (SHBG)		1 week, 4 weeks and 3 months
Secondary	Muscle strength as assessed by grip strength test		1 week, 4 weeks and 3 months
Secondary	Waist-hip-ratio		1 week, 4 weeks and 3 months
Secondary	BMI in kg/m2		1 week, 4 weeks and 3 months
Secondary	Insulin sensitivity as assessed by homeostasis model assessment insulin resistance (HOMA-IR)		1 week, 4 weeks and 3 months
Secondary	Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (mmol/l)		1 week, 4 weeks and 3 months
Secondary	Leptin (µg/l)		1 week, 4 weeks and 3 months