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

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ClinicalTrials.gov Identifier: NCT03578497
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE June 21, 2018
First Posted Date  ICMJE July 6, 2018
Last Update Posted Date May 13, 2020
Actual Study Start Date  ICMJE August 31, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra. [ Time Frame: 7 days ]
Absolute change in fasting serum androstenedione level (nmol/l) from start (baseline, day 1) to one week after treatment start with Anakinra.
Original Primary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
Absolute change in morning serum total testosterone level (nmol/l) from start (baseline, day 1) to end of treatment with Anakinra (28 days). [ Time Frame: 28 days ]
Absolute change in morning serum total testosterone level (nmol/l) from start (baseline, day 1) to end of treatment with Anakinra (28 days).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
  • Ferriman-Gallwey-score [ Time Frame: 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
  • Sebum production measures [ Time Frame: 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)
  • Self-reported frequency of hair removal (times/week) [ Time Frame: At day 1 and 28 ]
    Effect of Anakinra/Kineret® on hirsutism will be assessed
  • Plewig-Kligman-score [ Time Frame: 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 [%] [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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]) [ Time Frame: Day 1, 7, 14, 21, 28 and 35 ]
    Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed
  • Treatment response according to a Dexamethasone suppression test [ Time Frame: At days 35 and 36 ]
    Dexamethasone suppression test will be evaluated as a predictor for treatment response
  • inflammatory marker white blood cell count [x109/l], [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: Day 1 and 28 ]
    Time course of inflammatory marker IL-6 [pg/ml] will be assessed
  • inflammatory marker IL-1Ra [pg/ml] [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
  • Ferriman-Gallwey-score [ Time Frame: 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
  • Sebum production measures [ Time Frame: 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)
  • Self-reported frequency of hair removal (times/week) [ Time Frame: At day 1 and 28 ]
    Effect of Anakinra/Kineret® on hirsutism will be assessed
  • Plewig-Kligman-score [ Time Frame: 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 [%] [ Time Frame: 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), sex hormone-binding globulin (SHBG) [nmol/l], Anti-Muellerian Hormone [pmol/l], dehydroepiandrosterone (DHEA) [nmol/l]) [ Time Frame: 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) [ Time Frame: 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]) [ Time Frame: Day 1, 7, 14, 21, 28 and 35 ]
    Effect of Anakinra/Kineret® on the pituitary-gonadal axis will be assessed
  • Treatment response according to a Dexamethasone suppression test [ Time Frame: At days 35 and 36 ]
    Dexamethasone suppression test will be evaluated as a predictor for treatment response
  • inflammatory marker white blood cell count [x109/l], [ Time Frame: Day 1, 7, 14, 21, 28 and 35 ]
    Time course of inflammatory marker white blood cell count [x109/l] will be assessed
  • inflammatory marker CRP [mg/l] [ Time Frame: 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] [ Time Frame: Day 1, 7, 14, 21, 28 and 35 ]
    Time course of inflammatory marker IL-6 [pg/ml] will be assessed
  • inflammatory marker IL-1Ra [pg/ml] [ Time Frame: Day 1, 7, 14, 21, 28 and 35 ]
    Time course of inflammatory marker IL-1Ra [pg/ml] will be assessed
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Interleukin-1 Receptor Antagonism on Hyperandrogenemia in Women With Polycystic Ovary Syndrome
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Polycystic Ovary Syndrome
Intervention  ICMJE 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.
Other Name: Kineret
Study Arms  ICMJE Experimental: IL-1 receptor antagonist Anakinra 100 mg
Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB) is a recombinant, non-glycosylated form of the human IL-1Ra in a 100 mg/ 0.67 ml solution for subcutaneous injection. Anakinra/Kineret® is supplied in single use prefilled glass syringes with 27 gauge needles as a sterile, clear, colorless-to-white, preservative free solution for daily s.c. administration over a time period of 28 days.
Intervention: Drug: IL-1 receptor antagonist Anakinra
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 5, 2020)
18
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2018)
32
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mirjam Christ-Crain, Prof. Dr. MD +41 61 265 48 96 mirjam.christ-crain@usb.ch
Contact: Milica Popovic +41 61 328 56 92 milica.popovic@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03578497
Other Study ID Numbers  ICMJE 2018-00780; me16CC6
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mirjam Christ-Crain, Prof. Dr. MD University Hospital Basel, Dep. of Endocrinology, Diabetes and Metabolism
PRS Account University Hospital, Basel, Switzerland
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP