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

NCT02672592 | Completed Phase 3

• 1 other identifier: EKNZ 2015-376
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

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.

Conditions

Hypogonadism; Metabolic Syndrome X; Obesity

Keywords

Metabolic syndrome X; Hypogonadism; Testosterone; Inflammation; Obesity

Outcome Measures

Primary Outcomes (1)

• Total morning testosterone (nmol/l)

  4 weeks

Secondary Outcomes (31)

• Total morning testosterone (nmol/l)

  1 week and 3 months

• Free testosterone (nmol/l)

  1 week, 4 weeks and 3 months

• Bioavailable testosterone (nmol/l)

  1 week, 4 weeks and 3 months

• Erectile dysfunction as assessed by International Index of Erectile Function (IIEF) score

  1 week, 4 weeks and 3 months

• Clinical severity of hypogonadism as assessed by quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire

  1 week, 4 weeks and 3 months

Study Arms (2)

Anakinra

ACTIVE COMPARATOR

Anakinra//Kineret® 100mg s.c. bid

Drug: Anakinra

Placebo

PLACEBO COMPARATOR

Sodium Chloride 0.9% s.c. bid

Drug: Sodium Chloride 0.9%

Interventions

Anakinra DRUG

Anakinra 100mg s.c. bid

Also known as: KINERET

Anakinra

Sodium Chloride 0.9% DRUG

Sodium Chloride 0.9% s.c. bid

Also known as: NaCl 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (2)

University Department of Medicine, Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 33846498 DERIVED

• 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.

  PMID: 32275191 DERIVED

• 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.

  PMID: 31042669 DERIVED

• 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.

  PMID: 29939279 DERIVED

MeSH Terms

Conditions

Hypogonadism; Metabolic Syndrome; Obesity; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein; Sodium Chloride

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Mirjam Christ-Crain, Professor

  Endocrinology, Diabetes and Metabolism; University Hospital Basel

  PRINCIPAL INVESTIGATOR

• Beat Müller, Professor

  University Department of Medicine; Kantonsspital Aarau

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 3, 2016
• Study Start: January 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 13, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)