Clinical trial NCT03578497: Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polycystic Ovary Syndrome
Keywords: Interleukin-1 receptor antagonism
Kineret/Anakinra
testosteron
hyperandrogenemia
androstenedione
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2018-07-06
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.
timeFrame: 7 days
Secondary outcomes:
measure: Ferriman-Gallwey-score
timeFrame: Day 1 and 28
measure: Sebum production measures
timeFrame: At day 1 and 28
measure: Self-reported frequency of hair removal (times/week)
timeFrame: At day 1 and 28
measure: Plewig-Kligman-score
timeFrame: At day 1 and 28
measure: Ovulation and menstruation rates [%]
timeFrame: Between day 1 and day 35
measure: 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)
timeFrame: Day 1, 7, 14, 21, 28 and 35
measure: Fasting glucose (mmol/l), homeostatic model of assessment of insulin resistance (HOMA-IR)
timeFrame: At day 1, 7, 14, 21, 28 and 35
measure: Pituitary hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) [IU/L])
timeFrame: Day 1, 7, 14, 21, 28 and 35
measure: Treatment response according to a Dexamethasone suppression test
timeFrame: At days 35 and 36
measure: inflammatory marker white blood cell count [x109/l],
timeFrame: Day 1, 7, 14, 21, 28 and 35
measure: inflammatory marker C reactive protein (CRP) [mg/l]
timeFrame: Day 1, 7, 14, 21, 28 and 35
measure: inflammatory marker IL-6 [pg/ml]
timeFrame: Day 1 and 28
measure: inflammatory marker IL-1Ra [pg/ml]
timeFrame: Day 1, 7, 14, 21, 28 and 35
measure: Change in androstenedione level (nmol/l) from start (baseline, day 1) to days 14, 21, 28, and 35 after treatment start with Anakinra.
timeFrame: Days 14, 21, 28, and 35 after treatment start with Anakinra
measure: 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
timeFrame: Days 7, 14, 28, and 35 after treatment start with Anakinra
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel Endocrinology, Diabetes and Metabolism
Study officials:
affiliation: University Hospital Basel, Dep. of Endocrinology, Diabetes and Metabolism
name: Mirjam Christ-Crain, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: