Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Clinical Trial

— FertIL  

Official title:

Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome - a Prospective, Interventional, Single-arm, Open-label, Proof-of-concept Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03578497
• Other study ID #: 2018-00780; me16CC6
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2018
• Est. completion date: July 30, 2020

Study information

• Verified date: January 2021
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, interventional, open-label, single-arm, proof-of-concept study: 18 women with Polycystic Ovary Syndrome (PCOS) will be treated with 100 mg of Anakinra/Kineret® for 4 weeks. 1 week after last injection patients will have a follow-up and a dexamethasone visit after a dexamethasone suppression test. Goal of this study is to investigate the effect of the Interleukin 1( IL-1) receptor antagonist Anakinra/Kineret® on laboratory and clinical features in women with PCOS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 30, 2020
• Est. primary completion date: July 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed Consent as documented by signature

• Premenopausal women aged 18 years or older

• Onset of menarche =5 years ago

• Diagnosis of PCOS defined by the Rotterdam criteria

• High sensitivity C-reactive protein level =1 mg/l

• Follicular phase of menstrual cycle as evident by

• Serum estradiol level <200 pmol/l AND

• Serum progesterone level <8 ng/ml

• Willingness to use non-hormonal contraceptive measures adequate to prevent becoming pregnant during the study

Exclusion Criteria:

• Intake of any testosterone level modifying drugs in the 8 weeks prior to study inclusion,

• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to Anakinra/Kineret,

• Women who are pregnant or breast feeding,

• Female participants who are ovariectomized or hysterectomised or post-menopausal

• Known or suspected non-compliance, drug or alcohol abuse,

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

• Participation in another study with investigational drug within the 30 days preceding and during the present study,

• Previous enrolment into the current study,

• Enrolment of the investigator, his/her family members, employees and other dependent persons,

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

• Potentially severe immunosuppression or intake of other immunosuppressive drugs

• Severe hematologic disease

• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, active carcinoma),

• History of or suspected tuberculosis and/or hepatitis B/C

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• IL-1 receptor antagonist Anakinra
IL-1 receptor antagonist Anakinra is a recombinant, non-glycosylated form of the human IL-1Ra in a 100 mg/ 0.67 ml solution for subcutaneous injection. Standard dosage licensed by the FDA and European Medicines Agency (EMA) is 100 mg Anakinra daily. It is supplied in single use prefilled glass syringes with 27 gauge needles as a sterile, clear, colourless-to-white, preservative free solution for daily s.c. administration.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel Endocrinology, Diabetes and Metabolism	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	Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.	Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.	7 days
Secondary	Ferriman-Gallwey-score	Effect of Anakinra/Kineret® on hirsutism by Ferriman-Gallwey-score (representation of hair growth in a male pattern on a woman shown in four different degrees of severity ( 0= no hair growth; 1= light hair growth; 2= moderate hair growth; 4= severe hair growth) in 11 different body parts; namely the upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, arm, forearm, thigh, and lower leg) will be assessed	Day 1 and 28
Secondary	Sebum production measures	Effect of Anakinra/Kineret® on sebum production will be assessed with Sebumeter® SM 815, Courage + Khazaka electronic Gesellschaft mit beschränkter Haftung (GmbH)	At day 1 and 28
Secondary	Self-reported frequency of hair removal (times/week)	Effect of Anakinra/Kineret® on hirsutism will be assessed	At day 1 and 28
Secondary	Plewig-Kligman-score	Effect of Anakinra/Kineret® on acne severity, assessed with Plewig-Kligman score (presentation of comedonal and inflammatory acne severity, separately graded based on the number of lesions and type; lesion counting done at right side of the face, excluding other side, chest and back.	At day 1 and 28
Secondary	Ovulation and menstruation rates [%]	Effect of Anakinra/Kineret® on ovulation and menstruation rates will be assessed	Between day 1 and day 35
Secondary	Estradiol (pmol/l), free testosterone (nmol/l), total testosterone (nmol/l), sex hormone-binding globulin (SHBG) [nmol/l], Anti-Muellerian Hormone [pmol/l], dehydroepiandrosterone (DHEA) [nmol/l]), basal cortisol (nmol/l)	Effect of Anakinra/Kineret® on peripheral (sexual) hormones will be assessed	Day 1, 7, 14, 21, 28 and 35
Secondary	Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR)	Effect of Anakinra/Kineret® on glucose metabolism will be assessed	At day 1, 7, 14, 21, 28 and 35
Secondary	Pituitary hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) [IU/L])	Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed	Day 1, 7, 14, 21, 28 and 35
Secondary	Treatment response according to a Dexamethasone suppression test	Dexamethasone suppression test will be evaluated as a predictor for treatment response	At days 35 and 36
Secondary	inflammatory marker white blood cell count [x109/l],	Time course of inflammatory marker white blood cell count [x109/l] will be assessed	Day 1, 7, 14, 21, 28 and 35
Secondary	inflammatory marker C reactive protein (CRP) [mg/l]	Time course of inflammatory marker CRP [mg/l] will be assessed	Day 1, 7, 14, 21, 28 and 35
Secondary	inflammatory marker IL-6 [pg/ml]	Time course of inflammatory marker IL-6 [pg/ml] will be assessed	Day 1 and 28
Secondary	inflammatory marker IL-1Ra [pg/ml]	Time course of inflammatory marker IL-1Ra [pg/ml] will be assessed	Day 1, 7, 14, 21, 28 and 35
Secondary	Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.	Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.	Days 14, 21, 28, and 35 after treatment start with Anakinra
Secondary	Change in 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11ß-hydroxytestosterone, 11ß-hydroxyandrostenedione [nmol/l]) on days 7, 14, 28, and 35 after treatment start with Anakinra	Change in 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11ß-hydroxytestosterone, 11ß-hydroxyandrostenedione [nmol/l]) on days 7, 14, 28, and 35 after treatment start with Anakinra	Days 7, 14, 28, and 35 after treatment start with Anakinra