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Polycystic Ovary SyndromePhase 4ProPCO-RCTNCT04593459

Probiotic Intervention in PCOS

A Phase 4 study testing Probiotic and Metformin Hydrochloride in people with Polycystic Ovary Syndrome, run by Medical University of Graz at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 45 years, women only
Conditions the study is for
Polycystic Ovary Syndrome
What is being tested?
Probiotic and Metformin Hydrochloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
112 participants
Where
1 siteAustria
Study dates
3 Nov 2020to 16 Oct 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

  • Missing or withdrawn consent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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Austria1 site

  • Medical University of Graz, Division of Endocrinology and Diabetology

    Graz, Styria, 8036

Other trials in Austria

About this study

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

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.

Being tested
Probiotic, Metformin Hydrochloride, Probiotic Placebo
Keywords
PCOS, Probiotic, Metformin, RCT
Medical subject headings
Polycystic Ovary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProbioticDietary supplement

    See Arm description

  • Metformin HydrochlorideDrug

    See Arm description

  • Probiotic PlaceboDietary supplement

    See Arm description

Study groups in NCT04593459
Study groupRoleWhat they receive
ProbioticExperimentalProbiotic 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
Receives: Dietary Supplement: Probiotic
PlaceboPlacebo comparatorSimilar 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
Receives: Dietary Supplement: Probiotic Placebo
MetforminActive comparatorMetformin 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.
Receives: Drug: Metformin Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Free testosterone

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

    Measured: 6 months

Secondary outcomes (31)

  1. Anti-Müllerian hormone (AMH)

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

    Measured: 6 months

  2. Androstenedione

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

    Measured: 6 months

  3. Dehydroepiandrosterone-sulphate (DHEA-S)

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

    Measured: 6 months

  4. 17-Hydroxyprogesterone (17-OH-progesterone)

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

    Measured: 6 months

  5. 17-OH-estradiol

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

    Measured: 6 months

  6. Total testosterone

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

    Measured: 6 months

  7. 25-OH-cholecalciferol

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

    Measured: 6 months

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

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

    Measured: 6 months

  9. LH to FSH ratio

    Changes in LH to FSH ratio after intervention [1]

    Measured: 6 months

  10. 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]

    Measured: 6 months

  11. 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]

    Measured: 6 months

  12. 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

    Measured: 6 months

  13. 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]

    Measured: 6 months

  14. 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]

    Measured: 6 months

  15. 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))

    Measured: 6 months

  16. 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

    Measured: 6 months

  17. Body-mass-index (BMI)

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

    Measured: 6 months

  18. waist-to-hip ratio

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

    Measured: 6 months

  19. 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.

    Measured: 6 months

  20. Diaminooxidase

    Changes in serum diaminooxidase levels after intervention

    Measured: 6 months

  21. Stool and serum zonulin

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

    Measured: 6 months

  22. Lipopolysaccharide

    Changes in lipopolysaccharide levels after intervention

    Measured: 6 months

  23. Soluble cluster of differentiation (sCD14)

    Changes in sCD14 levels in serum after intervention

    Measured: 6 months

  24. Calprotectin

    Changes in stool calprotectin levels after intervention

    Measured: 6 months

  25. Bacterial DNA

    Changes in bacterial DNA amounts in serum after intervention

    Measured: 6 months

  26. Gut lumen and mucosa microbiome composition and metagenomic profile

    Measured from stool samples via 16S-RNA gene sequencing

    Measured: 6 months

  27. Phytoestrogen production

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

    Measured: 6 months

  28. 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

    Measured: 6 months

  29. 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.

    Measured: 6 months

  30. 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.

    Measured: 6 months

  31. 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

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2020
  2. Study start3 Nov 2020
  3. Primary completion16 Oct 2023
  4. Study completion16 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Probiotic vs placebo (double-blinded) vs metformin (open-label)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04593459
Sponsor's protocol ID
160120200001
Other IDs
2020-000228-20
Acronym
ProPCO-RCT
Status last verified
Mar 2024
First submitted
12 Oct 2020
Last updated
22 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • 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.

    PubMed 28045919

  • 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.

    PubMed 32492805

  • 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.

    PubMed 37062834

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Probiotic and Metformin Hydrochloride in people with Polycystic Ovary Syndrome, run by Medical University of Graz at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Free testosterone (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04593459, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.

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