Probiotic Intervention in PCOS

Polycystic Ovary Syndrome Clinical Trial

— ProPCO-RCT  

Official title:

Probiotic Dietary Intervention in Polycystic Ovary Syndrome (PCOS) - A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04593459
• Other study ID #: 160120200001
• Secondary ID: 2020-000228-20
• Status: Completed
• Phase: Phase 4
• Start date: November 3, 2020
• Est. completion date: October 16, 2023

Study information

• Verified date: March 2024
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: October 16, 2023
• Est. primary completion date: October 16, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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• Missing or withdrawn consent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

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Dietary Supplement:
• Probiotic
See Arm description

Drug:
• Metformin Hydrochloride
See Arm description

Dietary Supplement:
• Probiotic Placebo
See Arm description

Locations

Country	Name	City	State
Austria	Medical University of Graz, Division of Endocrinology and Diabetology	Graz	Styria

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Graz	Institut AllergoSan, Winclove Probiotics B.V.

Country where clinical trial is conducted

Austria, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lipid metabolism	Low-density lipoproteins (LDL), high-density lipoproteins (HDL), lipoprotein a (LP(a)), triacylglycerols	6 months
Other	Fluorescence-activated cell sorting (FACS) analysis	B cell subtypes measured via FACS from whole blood	6 months
Primary	Free testosterone	Changes in free testosterone levels [pg/ml] in serum after intervention	6 months
Secondary	Anti-Müllerian hormone (AMH)	Changes in AMH levels in serum after intervention [ng/ml]	6 months
Secondary	Androstenedione	Changes in androstenedione levels in serum after intervention [ng/ml]	6 months
Secondary	Dehydroepiandrosterone-sulphate (DHEA-S)	Changes in DHEA-S levels in serum after intervention [µg/ml]	6 months
Secondary	17-Hydroxyprogesterone (17-OH-progesterone)	Changes in 17-OH-progesterone levels in serum after intervention [ng/ml]	6 months
Secondary	17-OH-estradiol	Changes in 17-OH-estradiol levels in serum after intervention [ng/ml]	6 months
Secondary	Total testosterone	Changes in total testosterone levels in serum after intervention [ng/ml]	6 months
Secondary	25-OH-cholecalciferol	Changes in 25-OH-cholecalciferol levels in serum after intervention [ng/ml]	6 months
Secondary	Luteinizing hormone (LH), Follicle-stimulating hormone (FSH)	Changes in LH and FSH levels in serum after intervention [mU/ml]	6 months
Secondary	LH to FSH ratio	Changes in LH to FSH ratio after intervention [1]	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Body-mass-index (BMI)	BMI measured with the formula BMI=weight [kg]/height² [m]	6 months
Secondary	waist-to-hip ratio	Calculated with the formula: waist circumference/hip circumference [1]	6 months
Secondary	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
Secondary	Diaminooxidase	Changes in serum diaminooxidase levels after intervention	6 months
Secondary	Stool and serum zonulin	Changes in stool and serum zonulin levels after intervention [ng/ml]	6 months
Secondary	Lipopolysaccharide	Changes in lipopolysaccharide levels after intervention	6 months
Secondary	Soluble cluster of differentiation (sCD14)	Changes in sCD14 levels in serum after intervention	6 months
Secondary	Calprotectin	Changes in stool calprotectin levels after intervention	6 months
Secondary	Bacterial DNA	Changes in bacterial DNA amounts in serum after intervention	6 months
Secondary	Gut lumen and mucosa microbiome composition and metagenomic profile	Measured from stool samples via 16S-RNA gene sequencing	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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