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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000228-20 | EudraCT Number |
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| Name | Class |
|---|---|
| Institut AllergoSan | UNKNOWN |
| Winclove Probiotics B.V. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotic | Experimental | Probiotic product consisting of these 7 bacterial strains:
Additional ingredients: Corn starch, maltodextrin, fructo-oligosaccharides, galacto-oligosaccharides, polydextrose, plant proteins, potassium chloride, magnesium sulfate, bacterial strains, manganese sulfate, lactose, 2000 IU vitamin D Participants ingest one sachet of powder (5 grams) in 200 ml of water per day for 6 months |
|
| Placebo | Placebo Comparator | Similar to probiotic product in optics and smell, less ingredients and no bacterial strains or vitamin D Ingredients: Corn starch, maltodextrin, potassium chloride, magnesium sulphate, manganese sulphate |
|
| Metformin | Active Comparator | Metformin is an established drug for treating PCOS-related symptoms. The investigators are comparing the probiotic not only to a placebo group, but also to the benchmark treatment. Participants in the metformin arm will start treatment with 500 mg daily for the first week, then increasing the dose to 2x500 mg daily for the duration of the intervention. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probiotic | Dietary Supplement | See Arm description |
| |
| Metformin Hydrochloride |
| Measure | Description | Time Frame |
|---|---|---|
| Free testosterone | Changes in free testosterone levels [pg/ml] in serum after intervention | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-Müllerian hormone (AMH) | Changes in AMH levels in serum after intervention [ng/ml] | 6 months |
| Androstenedione | Changes in androstenedione levels in serum after intervention [ng/ml] |
| Measure | Description | Time Frame |
|---|---|---|
| Lipid metabolism | Low-density lipoproteins (LDL), high-density lipoproteins (HDL), lipoprotein a (LP(a)), triacylglycerols | 6 months |
| Fluorescence-activated cell sorting (FACS) analysis | B cell subtypes measured via FACS from whole blood |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Barbara Obermayer-Pietsch, Prof. MD | Medical University of Graz, Division of Endocrinology and Diabetology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Graz, Division of Endocrinology and Diabetology | Graz | Styria | 8036 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28045919 | Background | 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. | |
| 32492805 |
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For research and cooperation purposes, pseudonymized individual participant data may be shared with other researchers, the decision to do so lies with the principal investigator. In case of publication of our results in a peer-reviewed journal, all relevant data will be made publicly accessible without any personal information
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| D019936 | Probiotics |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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Probiotic vs placebo (double-blinded) vs metformin (open-label)
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Only the probiotic and placebo are blinded, metformin is an open intervention arm
| Drug |
See Arm description |
|
| Probiotic Placebo | Dietary Supplement | See Arm description |
|
| 6 months |
| Dehydroepiandrosterone-sulphate (DHEA-S) | Changes in DHEA-S levels in serum after intervention [µg/ml] | 6 months |
| 17-Hydroxyprogesterone (17-OH-progesterone) | Changes in 17-OH-progesterone levels in serum after intervention [ng/ml] | 6 months |
| 17-OH-estradiol | Changes in 17-OH-estradiol levels in serum after intervention [ng/ml] | 6 months |
| Total testosterone | Changes in total testosterone levels in serum after intervention [ng/ml] | 6 months |
| 25-OH-cholecalciferol | Changes in 25-OH-cholecalciferol levels in serum after intervention [ng/ml] | 6 months |
| Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) | Changes in LH and FSH levels in serum after intervention [mU/ml] | 6 months |
| LH to FSH ratio | Changes in LH to FSH ratio after intervention [1] | 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] | 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] | 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 | 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] | 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] | 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)) | 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 | 6 months |
| Body-mass-index (BMI) | BMI measured with the formula BMI=weight [kg]/height² [m] | 6 months |
| waist-to-hip ratio | Calculated with the formula: waist circumference/hip circumference [1] | 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. | 6 months |
| Diaminooxidase | Changes in serum diaminooxidase levels after intervention | 6 months |
| Stool and serum zonulin | Changes in stool and serum zonulin levels after intervention [ng/ml] | 6 months |
| Lipopolysaccharide | Changes in lipopolysaccharide levels after intervention | 6 months |
| Soluble cluster of differentiation (sCD14) | Changes in sCD14 levels in serum after intervention | 6 months |
| Calprotectin | Changes in stool calprotectin levels after intervention | 6 months |
| Bacterial DNA | Changes in bacterial DNA amounts in serum after intervention | 6 months |
| Gut lumen and mucosa microbiome composition and metagenomic profile | Measured from stool samples via 16S-RNA gene sequencing | 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 | 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 | 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. | 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. | 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 | 6 months |
| 6 months |
| Background |
| 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. |
| 37062834 | Derived | Borzan V, Riedl R, Obermayer-Pietsch B. Probiotic vs. placebo and metformin: probiotic dietary intervention in polycystic ovary syndrome - A randomized controlled trial. BMC Endocr Disord. 2023 Apr 17;23(1):82. doi: 10.1186/s12902-023-01294-6. |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D019602 |
| Food and Beverages |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |