Probiotic Intervention in PCOS

NCT04593459 | Completed Phase 4

• 2 other identifiers: 1601202000012020-000228-20
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Ovary Syndrome

Keywords

PCOS; Probiotic; Metformin; RCT

Outcome Measures

Primary Outcomes (1)

• Free testosterone

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

  6 months

Secondary Outcomes (31)

• Anti-Müllerian hormone (AMH)

  6 months

• Androstenedione

  6 months

• Dehydroepiandrosterone-sulphate (DHEA-S)

  6 months

• 17-Hydroxyprogesterone (17-OH-progesterone)

  6 months

• 17-OH-estradiol

  6 months

Other Outcomes (2)

• Lipid metabolism

  6 months

• Fluorescence-activated cell sorting (FACS) analysis

  6 months

Study Arms (3)

Probiotic

EXPERIMENTAL

Probiotic product consisting of these 7 bacterial strains: * Lactobacillus salivarius W57 * Lactobacillus casei W56 * Lactobacillus rhamnosus W71 * Lactococcus lactis W58 * Enterococcus faecium W54 * Lactobacillus plantarum W62 * Lactobacillus acidophilus W22 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

Dietary Supplement: Probiotic

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

Dietary Supplement: Probiotic Placebo

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.

Drug: Metformin Hydrochloride

Interventions

Probiotic DIETARY_SUPPLEMENT

See Arm description

Probiotic

Metformin Hydrochloride DRUG

See Arm description

Metformin

Probiotic Placebo DIETARY_SUPPLEMENT

See Arm description

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• Institut AllergoSan: collaborator
• Winclove Probiotics B.V.: collaborator

Study Sites (1)

Medical University of Graz, Division of Endocrinology and Diabetology

Graz, Styria, 8036, Austria

Location

Related Publications (3)

• 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.

  PMID: 28045919 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.

  PMID: 32492805 BACKGROUND

• 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.

  PMID: 37062834 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Probiotics; Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Barbara Obermayer-Pietsch, Prof. MD

  Medical University of Graz, Division of Endocrinology and Diabetology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the probiotic and placebo are blinded, metformin is an open intervention arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD

Model Details: Probiotic vs placebo (double-blinded) vs metformin (open-label)

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 20, 2020
• Study Start: November 3, 2020
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: to be determined
• Access Criteria: to be determined

Locations

AU (1)