Polycystic Ovary Syndrome
Conditions
Keywords
Interleukin-1 receptor antagonism, Kineret/Anakinra, testosteron, hyperandrogenemia, androstenedione
Brief 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.
Interventions
DRUGIL-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.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra. | 7 days | Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported frequency of hair removal (times/week) | At day 1 and 28 | Effect of Anakinra/Kineret® on hirsutism will be assessed |
| Ferriman-Gallwey-score | Day 1 and 28 | 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 |
| Plewig-Kligman-score | At day 1 and 28 | 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. |
| Ovulation and menstruation rates [%] | Between day 1 and day 35 | Effect of Anakinra/Kineret® on ovulation and menstruation rates will be assessed |
| 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) | Day 1, 7, 14, 21, 28 and 35 | Effect of Anakinra/Kineret® on peripheral (sexual) hormones will be assessed |
| Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR) | At day 1, 7, 14, 21, 28 and 35 | Effect of Anakinra/Kineret® on glucose metabolism will be assessed |
| Pituitary hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) [IU/L]) | Day 1, 7, 14, 21, 28 and 35 | Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed |
| Sebum production measures | At day 1 and 28 | Effect of Anakinra/Kineret® on sebum production will be assessed with Sebumeter® SM 815, Courage + Khazaka electronic Gesellschaft mit beschränkter Haftung (GmbH) |
| inflammatory marker white blood cell count [x109/l], | Day 1, 7, 14, 21, 28 and 35 | Time course of inflammatory marker white blood cell count \[x109/l\] will be assessed |
| inflammatory marker C reactive protein (CRP) [mg/l] | Day 1, 7, 14, 21, 28 and 35 | Time course of inflammatory marker CRP \[mg/l\] will be assessed |
| inflammatory marker IL-6 [pg/ml] | Day 1 and 28 | Time course of inflammatory marker IL-6 \[pg/ml\] will be assessed |
| inflammatory marker IL-1Ra [pg/ml] | Day 1, 7, 14, 21, 28 and 35 | Time course of inflammatory marker IL-1Ra \[pg/ml\] will be assessed |
| 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 | 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 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11β-hydroxytestosterone, 11β-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 | Change in 11-oxygenated androgens (e.g. 11-ketotestosterone, 11-ketoandrostenedione, 11β-hydroxytestosterone, 11β-hydroxyandrostenedione \[nmol/l\]) on days 7, 14, 28, and 35 after treatment start with Anakinra |
| Treatment response according to a Dexamethasone suppression test | At days 35 and 36 | Dexamethasone suppression test will be evaluated as a predictor for treatment response |
Countries
Switzerland
Outcome results
None listed