| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | Polycystic Ovary Syndrome (PCOS) is a hormonal and metabolic disorder
affecting up to 20 percent of women worldwide, depending on diagnostic
criteria. A very common definition of PCOS based on the revised
Rotterdam criteria includes at least two out of three symptoms:
• Oligo-/Amenorrhea
• Polycystic ovarian morphology (PCOM)
• Clinical or biochemical hyperandrogenism | Das Polyzystische Ovarsyndrom ist eine hormonelle und
Stoffwechselerkrankung, die bis zu 20% aller Frauen weltweit betrifft.
Die Diagnose von PCOS basiert auf mindestens zwei von drei möglichen
Rotterdam Kriterien:
• Oligo-/Amenorrhoe
• Polyzystische Ovarien Morphologie (PCOM)
• Klinischer oder biochemischer Hyperandrogenismus | |
| E.1.1.1 | Medical condition in easily understood language | Polycystic Ovary Syndrome (PCOS) is a hormonal and metabolic
disorder. Due to elevated male sex hormone levels, it can cause
menstrual irregularities as well as excess hair growth | Das Polyzystische Ovarsyndrom ist eine hormonelle und
Stoffwechselerkrankung, bei der erhöhte männliche Geschlechtshormone
einen unregelmäßigen Zyklus, mehr Haarwuchs verursachen | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Our primary aim is to establish probiotics as a possible PCOS treatment
option by showing a significant improvement of free testosterone levels
in comparison to placebo after a 6-month intervention period. | Unser primäres Ziel ist es, Probiotika als eine mögliche Therapie bei
PCOS zu etablieren, indem wir zeigen, dass eine 6-monatige Intervention
mit Probiotika statistisch signifikant besser ist als ein Placebo in der
Reduktion von freiem Testosteron im Blut. | |
| E.2.2 | Secondary objectives of the trial | Our secondary objectives are:
to compare the secondary outcome parameters to placebo and show a
significant improvement in the probiotic group
to compare the ourcome parameters of the probiotic treatment to
metformin | Als sekundäre Ziele wollen wir:
die Probiotikagruppe mit dem placebo vergleichen in Hinsicht auf die
sekundären Endpunkte
Die Probiotikagruppe mti der Metformingruppe vergleichen | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | Premenopausal women with PCOS aged 18 to 45 years meeting two
out of three Rotterdam criteria: polycystic ovarian morphology,
biochemical and/or clinical hyperandrogenism and oligo-/anovulation
Signed informed consent form | |
| E.4 | Principal exclusion criteria | Missing or withdrawn consent
Hyperandrogenism of a cause other than PCOS (Cushing´s syndrome,
hyperprolactinemia, adrenal tumours, congenital adrenal hyperplasia,
rare genetic disorders)
Pregnancy or nursing period (first 6 months after giving birth)
Soy or other allergies with respect to study procedures
Diabetes mellitus type 1
Chronic inflammatory bowel disease, history of cancer in the
gastrointestinal tract or acute gastrointestinal infection
Any malignancies that required treatment within the last 3 years
prior to study procedures
Any other chronic disease requiring medical check-ups or hospital
treatments at least once every three months (exception: diabetes
mellitus type 2)
Major surgery in the gastrointestinal tract (e.g. colectomy, gut
segment excision with stoma surgery, Whipple´s surgery.) Surgical
removal of the appendix and/or the gall bladder is NOT considered major
surgery.
Therapy with antidiabetic drugs (metformin, sulfonylureas, DPP-4
inhibitors, GLP-1 analogs, SGLT-2 inhibitors, insulin variants) within the
last six months prior to study procedures
Therapy with proton pump inhibitors within the last six months prior
to study procedures
Therapy with hormonal contraceptives or systemic (oral) intake of
steroids
Oral or intravenous therapy with antibiotics less than three months
before the onset of study procedures
Alcohol and/or drug abuse | |
| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint of the study is a change in serum free testosterone
concentration in women with PCOS after a 6-month intervention with
probiotics compared to placebo treatment. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | baseline, after 6 months intervention, and an additional 6 months (voluntary) follow-up | |
| E.5.2 | Secondary end point(s) | Glucose metabolism (Oral glucose tolerance test)
Other hormonal parameters of PCOS (AMH; androstenedione; FSH; LH; DHEAS; 17-OH-progesterone; 17-OH-estradiole;
dihydrotestosterone, total testosterone)
Hirsutism (modified Ferriman-Galway-score)
Body weight (BMI; waist-to-hip-ratio)
Gut permeability and inflammation (Functional sugar test; surrogate
parameters: serum diaminooxydase; stool zonulin; calprotectin;
lipopolysaccharide; soluble CD14; bacterial DNA)
Gut lumen and mucosa microbiome composition and metagenomic
profile (16S-RNA gene sequencing)
Phytoestrogen production (soy challenge test; urine daidzein and
equol concentrations)
Quality of life (PCOS questionnaire; depression questionnaires; diet
questionnaires) | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | baseline, after 6 months intervention, and an additional 6 months (voluntary) follow-up | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description | | Probiotics vs. placebo is double-blinded, metformin is open-labelled | |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | | metformin is our comparator; Our investogational product is a dietary supplement (probiotics) | |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | last visit of the last subject undergoing the trial
E. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
