Donnerstag, 28. Januar 2021
Navigation öffnen
Anzeige:
Canakinumab
 

JOURNAL ONKOLOGIE – STUDIE

ProPCO-RCT Probiotic Intervention in PCOS

Rekrutierend

NCT-Nummer:
NCT04593459

Studienbeginn:
November 2020

Letztes Update:
04.11.2020

Wirkstoff:
Metformin Hydrochloride

Indikation (Clinical Trials):
Polycystic Ovary Syndrome, Syndrome

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 4

Sponsor:
Medical University of Graz

Collaborator:
Institut AllergoSan, Winclove Probiotics,

Studienleiter

Barbara Obermayer-Pietsch, Prof. MD
Principal Investigator
Medical University of Graz, Division of Endocrinology and Diabetology

Kontakt

Valentin Borzan, MD
Kontakt:
Phone: 0043-316-385
Phone (ext.): 14290
E-Mail: valentin.borzan@medunigraz.at
» Kontaktdaten anzeigen
Barbara Obermayer-Pietsch, Prof. MD
Kontakt:
Phone: 0043-316-385
Phone (ext.): 12383
E-Mail: barbara.obermayer@medunigraz.at
» Kontaktdaten anzeigen

Studienlocations (1 von 1)

Medical University of Graz, Division of Endocrinology and Diabetology
8036 Graz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Barbara Obermayer-Pietsch, Prof. MD
Phone: +43316-385-80253
E-Mail: barbara.obermayer@medunigraz.at

Valentin Borzan, MD
Phone: +43316-385-14290
E-Mail: valentin.borzan@medunigraz.at
» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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- Missing or withdrawn consent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

Studien-Rationale

Primary outcome:

1. Free testosterone (Time Frame - 6 months):
Changes in free testosterone levels [pg/ml] in serum after intervention



Secondary outcome:

1. Anti-Müllerian hormone (AMH) (Time Frame - 6 months):
Changes in AMH levels in serum after intervention [ng/ml]

2. Androstenedione (Time Frame - 6 months):
Changes in androstenedione levels in serum after intervention [ng/ml]

3. Dehydroepiandrosterone-sulphate (DHEA-S) (Time Frame - 6 months):
Changes in DHEA-S levels in serum after intervention [µg/ml]

4. 17-Hydroxyprogesterone (17-OH-progesterone) (Time Frame - 6 months):
Changes in 17-OH-progesterone levels in serum after intervention [ng/ml]

5. 17-OH-estradiol (Time Frame - 6 months):
Changes in 17-OH-estradiol levels in serum after intervention [ng/ml]

6. Total testosterone (Time Frame - 6 months):
Changes in total testosterone levels in serum after intervention [ng/ml]

7. 25-OH-cholecalciferol (Time Frame - 6 months):
Changes in 25-OH-cholecalciferol levels in serum after intervention [ng/ml]

8. Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) (Time Frame - 6 months):
Changes in LH and FSH levels in serum after intervention [mU/ml]

9. LH to FSH ratio (Time Frame - 6 months):
Changes in LH to FSH ratio after intervention [1]

10. Insulin (Time Frame - 6 months):
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]

11. Glucose (Time Frame - 6 months):
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]

12. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index (Time Frame - 6 months):
Changes in HOMA-IR index (fasting insulin [mU/l] * fasting glucose [mg/dl]/405) after intervention

13. Glucose mean (Time Frame - 6 months):
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]

14. Insulin mean (Time Frame - 6 months):
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]

15. Matsuda index (Time Frame - 6 months):
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))

16. Hirsutism (Time Frame - 6 months):
measured by modified Ferriman-Gallwey-score (mFG-score), ranging from 0 to 36, with 0 being the best possible value and 36 the worst

17. Body-mass-index (BMI) (Time Frame - 6 months):
BMI measured with the formula BMI=weight [kg]/height² [m]

18. waist-to-hip ratio (Time Frame - 6 months):
Calculated with the formula: waist circumference/hip circumference [1]

19. Sucrose-lactulose-mannitol test (Time Frame - 6 months):
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.

20. Diaminooxidase (Time Frame - 6 months):
Changes in serum diaminooxidase levels after intervention

21. Stool and serum zonulin (Time Frame - 6 months):
Changes in stool and serum zonulin levels after intervention [ng/ml]

22. Lipopolysaccharide (Time Frame - 6 months):
Changes in lipopolysaccharide levels after intervention

23. Soluble cluster of differentiation (sCD14) (Time Frame - 6 months):
Changes in sCD14 levels in serum after intervention

24. Calprotectin (Time Frame - 6 months):
Changes in stool calprotectin levels after intervention

25. Bacterial DNA (Time Frame - 6 months):
Changes in bacterial DNA amounts in serum after intervention

26. Gut lumen and mucosa microbiome composition and metagenomic profile (Time Frame - 6 months):
Measured from stool samples via 16S-RNA gene sequencing

27. Phytoestrogen production (Time Frame - 6 months):
Changes in daidzein and equol concentrations after intervention [ng/ml] measured in urine samples of participants after ingestion of soy milk

28. Equol producer status (Time Frame - 6 months):
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

29. Quality of life (QOL) (Time Frame - 6 months):
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.

30. QOL (Time Frame - 6 months):
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.

31. QOL (Time Frame - 6 months):
Quality of Life measured by a PCOS questionnaire ranging from 0 to 156, with 0 being the best possible score and 156 the worst

Studien-Arme

  • Experimental: Probiotic
    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
  • Placebo Comparator: Placebo
    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
  • Active Comparator: Metformin
    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.

Geprüfte Regime

  • Probiotic:
    See Arm description
  • Metformin Hydrochloride:
    See Arm description
  • Probiotic Placebo:
    See Arm description

Quelle: ClinicalTrials.gov


ASH 2020
  • Phase-III-Studie ASCEMBL bei resistenten/intoleranten Patienten mit CML: STAMP-Inhibitor Asciminib deutlich effektiver als TKI Bosutinib
  • Ruxolitinib-resistente/-intolerante MF-Patienten profitieren im klinischen Alltag möglicherweise von einer Rechallenge
  • Real-world-Daten zu PV: Rechtzeitige Umstellung von HU auf Ruxolitinib wirkt möglicherweise Anstieg thromboembolischer Ereignisse entgegen
  • 5-Jahres-Daten der RESPONSE-2-Studie: Überlegenheit von Ruxolitinib gegenüber BAT im Langzeitverlauf bestätigt
  • Phase-I-Studie: Anhaltendes molekulares Ansprechen mit neuem BCR-ABL-Inhibitor Asciminib bei CML-Patienten mit T315I-Resistenzmutation
  • Patienten mit ITP sind emotional erheblich belastet
  • r/r DLBCL: Vielversprechende erste Daten zur CAR-T-Zell-Therapie mit Tisagenlecleucel in Kombination mit Ibrutinib
  • r/r FL: CAR-T-Zell-Therapie mit Tisagenlecleucel wirksam und sicher
  • Myelofibrose: Ruxolitinib-Startdosis von 10 mg 2x tägl. auch bei initial niedriger Thrombozytenzahl sicher anwendbar
  • Phase-III-Studie REACH3: Ruxolitinib bei chronischer steroidrefraktärer oder steroidabhängiger GvHD wirksamer als die beste verfügbare Therapie