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

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ClinicalTrials.gov Identifier: NCT02672592
Recruitment Status : Completed
First Posted : February 3, 2016
Last Update Posted : July 13, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Hypogonadism Metabolic Syndrome X Obesity Drug: Anakinra Drug: Sodium Chloride 0.9% Phase 3

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of IL-1 Beta on the Hypothalamic-pituitary-gonadal (HPG) Axis in Men With Obesity and Metabolic Syndrome - The TestIL Trial
Study Start Date : January 2016
Actual Primary Completion Date : June 2017
Actual Study Completion Date : June 2017

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Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Anakinra
Anakinra//Kineret® 100mg s.c. bid
 Drug: Anakinra
Anakinra 100mg s.c. bid
Other Name: KINERET
Placebo Comparator: Placebo
Sodium Chloride 0.9% s.c. bid
 Drug: Sodium Chloride 0.9%
Sodium Chloride 0.9% s.c. bid
Other Name: NaCl 0.9%


Outcome Measures
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Primary Outcome Measures :
  1. Total morning testosterone (nmol/l) [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Total morning testosterone (nmol/l) [ Time Frame: 1 week and 3 months ]
  2. Free testosterone (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
    Assessed by equilibrium dialysis

  3. Bioavailable testosterone (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
    Assessed by equilibrium dialysis

  4. Erectile dysfunction as assessed by International Index of Erectile Function (IIEF) score [ Time Frame: 1 week, 4 weeks and 3 months ]
  5. Clinical severity of hypogonadism as assessed by quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire [ Time Frame: 1 week, 4 weeks and 3 months ]
  6. Proportion of muscle mass as assessed by bioelectrical impedance Analysis [ Time Frame: 1 week, 4 weeks and 3 months ]
  7. Proportion of fat mass as assessed by bioelectrical impedance Analysis [ Time Frame: 1 week, 4 weeks and 3 months ]
  8. HbA1c (%) [ Time Frame: 1 week, 4 weeks and 3 months ]
  9. LH and FSH (IU/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  10. Inhibin B, ACTH (pg/ml) [ Time Frame: 1 week, 4 weeks and 3 months ]
  11. Prolactin, TSH, Insulin (mIU/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  12. Interleukin-1, Interleukin-6 (pg/ml) [ Time Frame: 1 week, 4 weeks and 3 months ]
  13. Cortisol basal (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  14. C-reactive protein (mg/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  15. free T4 (pmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  16. T3 (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  17. IGF-1 (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  18. GH (mU/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  19. Androstendione (μg/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  20. DHEAS (μmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  21. Oestradiol (pmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  22. Oestron (ng/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  23. 17-OH-progesterone (nmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  24. Copeptin (pmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  25. Sex hormone-binding globulin (SHBG) [ Time Frame: 1 week, 4 weeks and 3 months ]
  26. Muscle strength as assessed by grip strength test [ Time Frame: 1 week, 4 weeks and 3 months ]
  27. Waist-hip-ratio [ Time Frame: 1 week, 4 weeks and 3 months ]
  28. BMI in kg/m2 [ Time Frame: 1 week, 4 weeks and 3 months ]
  29. Insulin sensitivity as assessed by homeostasis model assessment insulin resistance (HOMA-IR) [ Time Frame: 1 week, 4 weeks and 3 months ]
  30. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (mmol/l) [ Time Frame: 1 week, 4 weeks and 3 months ]
  31. Leptin (μg/l) [ Time Frame: 1 week, 4 weeks and 3 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02672592


Locations
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Switzerland
University Department of Medicine, Kantonsspital Aarau
Aarau, Switzerland, 5001
University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
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Principal Investigator: Mirjam Christ-Crain, Professor Endocrinology, Diabetes and Metabolism; University Hospital Basel
Principal Investigator: Beat Müller, Professor University Department of Medicine; Kantonsspital Aarau
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02672592    
Other Study ID Numbers: EKNZ 2015-376
First Posted: February 3, 2016    Key Record Dates
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University Hospital, Basel, Switzerland:
Metabolic syndrome X
Hypogonadism
Testosterone
Inflammation
Obesity
Additional relevant MeSH terms:
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Microvascular Angina
Obesity
Metabolic Syndrome
Hypogonadism
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
 Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Gonadal Disorders
Endocrine System Diseases
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents