Clinical trial NCT04593459: Probiotic Intervention in PCOS
Official title: Probiotic Dietary Intervention in Polycystic Ovary Syndrome (PCOS) - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Keywords: PCOS
Probiotic
Metformin
RCT
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Institut AllergoSan
name: Winclove Probiotics B.V.
First posted: 2020-10-20
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Probiotic vs placebo (double-blinded) vs metformin (open-label)
Primary purpose: TREATMENT

Brief summary: The investigators are conducting a double-blinded randomized controlled trial to determine whether a probiotic mixture is effective in reducing PCOS-related symptoms. For this purpose, 180 participants will be recruited in three intervention arms (Probiotic, Placebo and Metformin), with 60 participants per arm. The intervention period will last 6 months, with extensive medical history, blood work, urine and stool analysis at the beginning and the conclusion of the trial.


Eligibility criteria: Inclusion Criteria:

* Polycystic Ovary Syndrome diagnosed based on at least two out of three rotterdam criteria: hyperandrogenism, polycystic ovarian morphology, oligo-/anovulation
* signed informed consent

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* Missing or withdrawn consent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, dipeptidyl peptidase 4 (DPP-4) inhibitors, Glucagon-like peptide 1 (GLP-1) analogs, sodium-glucose-cotransporter 2 (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 within the last six months prior to study procedures
* Oral or intravenous therapy with antibiotics less than three months before the onset of study procedures
* Alcohol and/or drug abuse

Primary outcomes:
measure: Free testosterone
timeFrame: 6 months
Secondary outcomes:
measure: Anti-Müllerian hormone (AMH)
timeFrame: 6 months
measure: Androstenedione
timeFrame: 6 months
measure: Dehydroepiandrosterone-sulphate (DHEA-S)
timeFrame: 6 months
measure: 17-Hydroxyprogesterone (17-OH-progesterone)
timeFrame: 6 months
measure: 17-OH-estradiol
timeFrame: 6 months
measure: Total testosterone
timeFrame: 6 months
measure: 25-OH-cholecalciferol
timeFrame: 6 months
measure: Luteinizing hormone (LH), Follicle-stimulating hormone (FSH)
timeFrame: 6 months
measure: LH to FSH ratio
timeFrame: 6 months
measure: Insulin
timeFrame: 6 months
measure: Glucose
timeFrame: 6 months
measure: Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index
timeFrame: 6 months
measure: Glucose mean
timeFrame: 6 months
measure: Insulin mean
timeFrame: 6 months
measure: Matsuda index
timeFrame: 6 months
measure: Hirsutism
timeFrame: 6 months
measure: Body-mass-index (BMI)
timeFrame: 6 months
measure: waist-to-hip ratio
timeFrame: 6 months
measure: Sucrose-lactulose-mannitol test
timeFrame: 6 months
measure: Diaminooxidase
timeFrame: 6 months
measure: Stool and serum zonulin
timeFrame: 6 months
measure: Lipopolysaccharide
timeFrame: 6 months
measure: Soluble cluster of differentiation (sCD14)
timeFrame: 6 months
measure: Calprotectin
timeFrame: 6 months
measure: Bacterial DNA
timeFrame: 6 months
measure: Gut lumen and mucosa microbiome composition and metagenomic profile
timeFrame: 6 months
measure: Phytoestrogen production
timeFrame: 6 months
measure: Equol producer status
timeFrame: 6 months
measure: Quality of life (QOL)
timeFrame: 6 months
measure: QOL
timeFrame: 6 months
measure: QOL
timeFrame: 6 months
Other outcomes:
measure: Lipid metabolism
timeFrame: 6 months
measure: Fluorescence-activated cell sorting (FACS) analysis
timeFrame: 6 months
Locations:
city: Graz
country: Austria
facility: Medical University of Graz, Division of Endocrinology and Diabetology
state: Styria
Study officials:
affiliation: Medical University of Graz, Division of Endocrinology and Diabetology
name: Barbara Obermayer-Pietsch, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lindheim L, Bashir M, Munzker J, Trummer C, Zachhuber V, Leber B, Horvath A, Pieber TR, Gorkiewicz G, Stadlbauer V, Obermayer-Pietsch B. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study. PLoS One. 2017 Jan 3;12(1):e0168390. doi: 10.1371/journal.pone.0168390. eCollection 2017.
citation: Haudum C, Lindheim L, Ascani A, Trummer C, Horvath A, Munzker J, Obermayer-Pietsch B. Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics. Nutrients. 2020 Jun 1;12(6):1622. doi: 10.3390/nu12061622.