Back to resultsEffects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome (TestIL)
Primary Purpose
Hypogonadism, Metabolic Syndrome X, Obesity
Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Anakinra
Sodium Chloride 0.9%
Sponsored by
About this trial
This is an interventional treatment trial for Hypogonadism focused on measuring Metabolic syndrome X, Hypogonadism, Testosterone, Inflammation, Obesity
Eligibility Criteria
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.
Sites / Locations
- University Department of Medicine, Kantonsspital Aarau
- University Hospital Basel
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Anakinra
Placebo
Arm Description
Anakinra//Kineret® 100mg s.c. bid
Sodium Chloride 0.9% s.c. bid
Outcomes
Primary Outcome Measures
Total morning testosterone (nmol/l)
Secondary Outcome Measures
Total morning testosterone (nmol/l)
Free testosterone (nmol/l)
Assessed by equilibrium dialysis
Bioavailable testosterone (nmol/l)
Assessed by equilibrium dialysis
Erectile dysfunction as assessed by International Index of Erectile Function (IIEF) score
Clinical severity of hypogonadism as assessed by quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire
Proportion of muscle mass as assessed by bioelectrical impedance Analysis
Proportion of fat mass as assessed by bioelectrical impedance Analysis
HbA1c (%)
LH and FSH (IU/l)
Inhibin B, ACTH (pg/ml)
Prolactin, TSH, Insulin (mIU/l)
Interleukin-1, Interleukin-6 (pg/ml)
Cortisol basal (nmol/l)
C-reactive protein (mg/l)
free T4 (pmol/l)
T3 (nmol/l)
IGF-1 (nmol/l)
GH (mU/l)
Androstendione (μg/l)
DHEAS (μmol/l)
Oestradiol (pmol/l)
Oestron (ng/l)
17-OH-progesterone (nmol/l)
Copeptin (pmol/l)
Sex hormone-binding globulin (SHBG)
Muscle strength as assessed by grip strength test
Waist-hip-ratio
BMI in kg/m2
Insulin sensitivity as assessed by homeostasis model assessment insulin resistance (HOMA-IR)
Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (mmol/l)
Leptin (μg/l)
Full Information
NCT ID
NCT02672592
First Posted
January 22, 2016
Last Updated
July 10, 2017
Sponsor
University Hospital, Basel, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT02672592
Brief Title
Effects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Metabolic Syndrome X, Obesity
Keywords
Metabolic syndrome X, Hypogonadism, Testosterone, Inflammation, Obesity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anakinra
Arm Type
Active Comparator
Arm Description
Anakinra//Kineret® 100mg s.c. bid
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Sodium Chloride 0.9% s.c. bid
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
KINERET
Intervention Description
Anakinra 100mg s.c. bid
Intervention Type
Drug
Intervention Name(s)
Sodium Chloride 0.9%
Other Intervention Name(s)
NaCl 0.9%
Intervention Description
Sodium Chloride 0.9% s.c. bid
Primary Outcome Measure Information:
Title
Total morning testosterone (nmol/l)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Total morning testosterone (nmol/l)
Time Frame
1 week and 3 months
Title
Free testosterone (nmol/l)
Description
Assessed by equilibrium dialysis
Time Frame
1 week, 4 weeks and 3 months
Title
Bioavailable testosterone (nmol/l)
Description
Assessed by equilibrium dialysis
Time Frame
1 week, 4 weeks and 3 months
Title
Erectile dysfunction as assessed by International Index of Erectile Function (IIEF) score
Time Frame
1 week, 4 weeks and 3 months
Title
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
Title
Proportion of muscle mass as assessed by bioelectrical impedance Analysis
Time Frame
1 week, 4 weeks and 3 months
Title
Proportion of fat mass as assessed by bioelectrical impedance Analysis
Time Frame
1 week, 4 weeks and 3 months
Title
HbA1c (%)
Time Frame
1 week, 4 weeks and 3 months
Title
LH and FSH (IU/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Inhibin B, ACTH (pg/ml)
Time Frame
1 week, 4 weeks and 3 months
Title
Prolactin, TSH, Insulin (mIU/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Interleukin-1, Interleukin-6 (pg/ml)
Time Frame
1 week, 4 weeks and 3 months
Title
Cortisol basal (nmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
C-reactive protein (mg/l)
Time Frame
1 week, 4 weeks and 3 months
Title
free T4 (pmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
T3 (nmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
IGF-1 (nmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
GH (mU/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Androstendione (μg/l)
Time Frame
1 week, 4 weeks and 3 months
Title
DHEAS (μmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Oestradiol (pmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Oestron (ng/l)
Time Frame
1 week, 4 weeks and 3 months
Title
17-OH-progesterone (nmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Copeptin (pmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Sex hormone-binding globulin (SHBG)
Time Frame
1 week, 4 weeks and 3 months
Title
Muscle strength as assessed by grip strength test
Time Frame
1 week, 4 weeks and 3 months
Title
Waist-hip-ratio
Time Frame
1 week, 4 weeks and 3 months
Title
BMI in kg/m2
Time Frame
1 week, 4 weeks and 3 months
Title
Insulin sensitivity as assessed by homeostasis model assessment insulin resistance (HOMA-IR)
Time Frame
1 week, 4 weeks and 3 months
Title
Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (mmol/l)
Time Frame
1 week, 4 weeks and 3 months
Title
Leptin (μg/l)
Time Frame
1 week, 4 weeks and 3 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mirjam Christ-Crain, Professor
Organizational Affiliation
Endocrinology, Diabetes and Metabolism; University Hospital Basel
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Beat Müller, Professor
Organizational Affiliation
University Department of Medicine; Kantonsspital Aarau
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Department of Medicine, Kantonsspital Aarau
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33846498
Citation
Ebrahimi F, Urwyler SA, Betz MJ, Christ ER, Schuetz P, Mueller B, Donath MY, Christ-Crain M. Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome. Sci Rep. 2021 Apr 12;11(1):7911. doi: 10.1038/s41598-021-87207-w.
Results Reference
derived
PubMed Identifier
32275191
Citation
Urwyler SA, Ebrahimi F, Burkard T, Schuetz P, Poglitsch M, Mueller B, Donath MY, Christ-Crain M. IL (Interleukin)-1 Receptor Antagonist Increases Ang (Angiotensin [1-7]) and Decreases Blood Pressure in Obese Individuals. Hypertension. 2020 Jun;75(6):1455-1463. doi: 10.1161/HYPERTENSIONAHA.119.13982. Epub 2020 Apr 10.
Results Reference
derived
PubMed Identifier
31042669
Citation
Ebrahimi F, Urwyler SA, Schuetz P, Mueller B, Bernasconi L, Neyer P, Donath MY, Christ-Crain M. Effects of interleukin-1 antagonism on cortisol levels in individuals with obesity: a randomized clinical trial. Endocr Connect. 2019 Jun 1;8(6):701-708. doi: 10.1530/EC-19-0201.
Results Reference
derived
PubMed Identifier
29939279
Citation
Ebrahimi F, Urwyler SA, Straumann S, Doerpfeld S, Bernasconi L, Neyer P, Schuetz P, Mueller B, Donath MY, Christ-Crain M. IL-1 Antagonism in Men With Metabolic Syndrome and Low Testosterone: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3466-3476. doi: 10.1210/jc.2018-00739.
Results Reference
derived
Learn more about this trial
Effects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome
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