Probiotic Intervention in PCOS

Medical University of Graz112 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

112

Conditions

Polycystic Ovary Syndrome

Interventions

ProbioticDIETARY_SUPPLEMENT

See Arm description

Metformin HydrochlorideDRUG

See Arm description

Probiotic PlaceboDIETARY_SUPPLEMENT

See Arm description

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

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polycystic ovarian morphology, oligo-/anovulation * signed informed consent Exclusion Criteria: * Missing or withdrawn consent * Hyperandrogenism of a cause other than PCOS (Cushing´s syndrome, hyperprolactinemia, adrenal tumours, congenital adrenal hyperplasia, rare genetic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

Locations (1)

Medical University of Graz, Division of Endocrinology and Diabetology

Graz, Styria, Austria

Outcomes

Primary Outcomes

Free testosterone

Changes in free testosterone levels \[pg/ml\] in serum after intervention

Time frame: 6 months

Secondary Outcomes

Anti-Müllerian hormone (AMH)

Changes in AMH levels in serum after intervention \[ng/ml\]

Time frame: 6 months

Androstenedione

Changes in androstenedione levels in serum after intervention \[ng/ml\]

Time frame: 6 months

Dehydroepiandrosterone-sulphate (DHEA-S)

Changes in DHEA-S levels in serum after intervention \[µg/ml\]

Time frame: 6 months

17-Hydroxyprogesterone (17-OH-progesterone)

Changes in 17-OH-progesterone levels in serum after intervention \[ng/ml\]

Time frame: 6 months

17-OH-estradiol

Changes in 17-OH-estradiol levels in serum after intervention \[ng/ml\]

Time frame: 6 months

Total testosterone

Changes in total testosterone levels in serum after intervention \[ng/ml\]

Time frame: 6 months

25-OH-cholecalciferol

Changes in 25-OH-cholecalciferol levels in serum after intervention \[ng/ml\]

Time frame: 6 months

Luteinizing hormone (LH), Follicle-stimulating hormone (FSH)

Data from ClinicalTrials.gov

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Changes in LH and FSH levels in serum after intervention \[mU/ml\]

Time frame: 6 months

LH to FSH ratio

Changes in LH to FSH ratio after intervention \[1\]

Time frame: 6 months

Insulin

Changes in insulin levels in serum as measured with a two-hour oral glucose tolerance test (75 mg glucose in 300 ml water, blood draws at 0 minutes, 30 min, 60 min and 120 min) \[mU/l\]

Time frame: 6 months

Glucose

Changes in glucose levels in sodium-fluoride plasma as measured with a two-hour oral glucose tolerance test (75 mg glucose in 300 ml water, blood draws at 0 minutes, 30 min, 60 min and 120 min) \[mg/dl\]

Time frame: 6 months

Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index

Changes in HOMA-IR index (fasting insulin \[mU/l\] \* fasting glucose \[mg/dl\]/405) after intervention

Time frame: 6 months

Glucose mean

Changes in mean glucose levels (measured with oral glucose tolerance test with the formula g=(glucose0 + 2\*glucose30 + 3\*glucose60 + 2\*glucose120)/8 \[mg/dl\]

Time frame: 6 months

Insulin mean

Changes in mean insulin levels (measured with oral glucose tolerance test with the formula i=(insulin0 + 2\*insulin30 + 3\*insulin0 + 2\*insulin120)/8 \[mU/l\]

Time frame: 6 months

Matsuda index

Changes in matsuda index after intervention measured with the formula M=10000/squareroot(glucose0 \* insulin0 \* glucose mean (see outcome 14) \* insulin mean (see outcome 15))

Time frame: 6 months

Hirsutism

measured by modified Ferriman-Gallwey-score (mFG-score), ranging from 0 to 36, with 0 being the best possible value and 36 the worst

Time frame: 6 months

Body-mass-index (BMI)

BMI measured with the formula BMI=weight \[kg\]/height² \[m\]

Time frame: 6 months

waist-to-hip ratio

Calculated with the formula: waist circumference/hip circumference \[1\]

Time frame: 6 months

Sucrose-lactulose-mannitol test

Functional gut permeability test consisting of ingesting 20 g sucrose, 5 g mannitol and 10 g lactulose in 100 ml water solution. Measurement of those three component concentrations in urine collected for 5 hours after solution ingestion by the participants. Lactulose to mannitol ratio may be calculated.

Time frame: 6 months

Diaminooxidase

Changes in serum diaminooxidase levels after intervention

Time frame: 6 months

Stool and serum zonulin

Changes in stool and serum zonulin levels after intervention \[ng/ml\]

Time frame: 6 months

Lipopolysaccharide

Changes in lipopolysaccharide levels after intervention

Time frame: 6 months

Soluble cluster of differentiation (sCD14)

Changes in sCD14 levels in serum after intervention

Time frame: 6 months

Calprotectin

Changes in stool calprotectin levels after intervention

Time frame: 6 months

Bacterial DNA

Changes in bacterial DNA amounts in serum after intervention

Time frame: 6 months

Gut lumen and mucosa microbiome composition and metagenomic profile

Measured from stool samples via 16S-RNA gene sequencing

Time frame: 6 months

Phytoestrogen production

Changes in daidzein and equol concentrations after intervention \[ng/ml\] measured in urine samples of participants after ingestion of soy milk

Time frame: 6 months

Equol producer status

Equol producer status as determined by the decadic logarithm of the equol/daidzein ratio \[1\]: A value above -0.5 is defined as an equol producer

Time frame: 6 months

Quality of life (QOL)

QOL assessed by General Depression Scale (German: Allgemeine Depressionsskala), German equivalent of the Depression Scale by the Center for Epidemiological Studies (CES-D). The scale ranges from 0 to 60, with 0 being the best possible score and 60 the worst.

Time frame: 6 months

QOL

QOL assessed by Beck´s Depression Inventory (BDI), a scale ranging from 0 to 63, with 0 being the best possible score and 63 the worst.

Time frame: 6 months

QOL

Quality of Life measured by a PCOS questionnaire ranging from 0 to 156, with 0 being the best possible score and 156 the worst

Time frame: 6 months