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Unexplained InfertilityPhase 2NCT04955574

Probiotic and Antibiotic Therapies in Women With Unexplained Infertility

A Phase 2 study testing SH-DS01 + Metronidazole in people with Unexplained Infertility and Endometriosis, run by McMaster University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The study is designed as a proof of concept pilot study with 3 study arms to evaluate the safety and feasibility of the use of oral probiotics and/or antibiotics in women with unexplained infertility/endometriosis. Read more about this study

Who is it for?
Ages 18 to 40 years, women only
Conditions the study is for
Unexplained Infertility, Endometriosis
What is being tested?
SH-DS01 + Metronidazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2023to Dec 2024
Phase
Phase 2
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 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Female aged 18-40 at the time of egg retrieval
  • Generally in good health (at physician's discretion)
  • Diagnosed with Unexplained Infertility
  • Diagnosed with or suspected of having endometriosis (at ONE Fertility physician's discretion)
  • Normal uterine cavity as assessed by prior sonohysterogram
  • Planning to undergo Frozen Embryo Transfer with ≥1 frozen blastocyst ≥3BB (grade Gardner) to transfer
  • Able to understand, comply and consent to protocol requirements and instructions
  • Able to attend scheduled study visits and complete required investigations

Who cannot join

  • Any known endometrial pathologies other than endometriosis
  • Polycystic ovary syndrome
  • Ovulatory dysfunction
  • Male factor infertility (Total Motile Sperm Count <5M/mL)
  • Poorly controlled auto-immune disease and/or diabetes (at physician's discretion)
  • Is immune-compromised
Show all 26Show fewer
  • Cockayne syndrome
  • Allergy to Metronidazole
  • Allergy to rice (bran and hull), pomegranate, Acacia gum, hypromellose, fermented gellan gum, chlorophyllin, or sunflower oil
  • Known intolerance of Lactobacillus and/or Bifidobacterium-containing probiotics
  • Antibiotic use in the past month
  • Use of any of the following:
  • Oral probiotics
  • Alcohol
  • Anticoagulant therapies (Warfarin type)
  • Drugs containing alcohol
  • Busulfan
  • Cyclosporin
  • Disulfiram
  • 5-Fluoruracil
  • Lithium
  • Phenytoin or Phenobarbital
  • Vecuronium
  • Proton pump inhibitors
  • Histamine H2-receptor antagonists
  • Currently experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain

About this study

The study is designed as a proof of concept pilot study with 3 study arms to evaluate the safety and feasibility of the use of oral probiotics and/or antibiotics in women with unexplained infertility/endometriosis. Our secondary outcomes will assess In Vitro Fertilization outcomes, and changes in the uterine microbiota (bacteria), intestinal barrier integrity, and urinary metabolites in response to study interventions.

Read the detailed description

Previous research has demonstrated that the uterine microbiota can impact fertility and embryo implantation. This information leads to the hypothesis that prophylactic antibiotic and/or probiotic treatment may improve reproductive outcomes in women with unexplained infertility/endometriosis who are seeking In Vitro Fertilization (IVF). No therapeutic protocols to improve these outcomes currently exist. However, there are safe and easily accessible medications and supplements that may be able to optimally modify the uterine microbiota. Herein we are proposing a proof of concept pilot study of the feasibility, safety and tolerability of administering oral probiotics, or oral probiotics in combination with antibiotics, to women seeking IVF.

Being tested
SH-DS01 + Antibiotic Placebo, SH-DS01 + Metronidazole, Probiotic Placebo + Antibiotic Placebo
Keywords
Uterine microbiota, Endometrial microbiota
Medical subject headings
Endometriosis

What participants receive

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

  • SH-DS01 + Antibiotic PlaceboOther

    Participants will be instructed to take 2 capsules of SH-DS01 probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of SH-DS01 probiotic once daily (at lunch) and 1 capsule of placebo for antibiotic twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

  • SH-DS01 + MetronidazoleDrug

    Participants will be instructed to take 2 capsules of SH-DS01 probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of SH-DS01 probiotic once daily (at lunch) and 1 capsule of 500mg metronidazole twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

  • Probiotic Placebo + Antibiotic PlaceboOther

    Participants will be instructed to take 2 capsules of placebo for probiotic once daily (at lunch) from cycle day 1 to the day of ovulation/day of luteal progesterone initiation, followed by 2 capsules of placebo for probiotic once daily (at lunch) and 1 capsule of placebo for antibiotic twice daily (at breakfast and dinner) from the day of ovulation/day of luteal progesterone initiation to the day of frozen embryo transfer.

Study groups in NCT04955574
Study groupRoleWhat they receive
Probiotic + Antibiotic PlaceboExperimentalNot described
Receives: Other: SH-DS01 + Antibiotic Placebo
Probiotic + AntibioticExperimentalNot described
Receives: Drug: SH-DS01 + Metronidazole
Probiotic Placebo + Antibiotic PlaceboPlacebo comparatorNot described
Receives: Other: Probiotic Placebo + Antibiotic Placebo

What is being measured

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

  1. Rate of study enrollment

    Evaluated by number of eligible participants consenting to enrollment in the study.

    Measured: Screening

  2. Rate of retention of study participants

    Evaluated by number of study participants who complete, drop out or withdraw from the study.

    Measured: Immediately after the intervention

  3. Proportion of participants adhering to study protocol

    Evaluated as the percentage of study participants reporting daily administration of study interventions throughout the intervention period.

    Measured: Immediately after the intervention

  4. Incidence of intervention-emergent adverse events

    Evaluated as the percentage of adverse events occurring in each intervention group.

    Measured: Immediately after the intervention

Secondary outcomes (8)

  1. Difference in implantation rate

    Evaluated by number of people with a positive beta hCG 2 weeks following frozen embryo transfer (FET), between intervention groups.

    Measured: Endpoint of interventions to 4 weeks gestation (if applicable)

  2. Difference in clinical pregnancy rate

    Evaluated by number of people with a clinical pregnancy (gestational sac with fetal pole and cardiac activity seen on ultrasound at 6 weeks gestation), between intervention groups.

    Measured: Endpoint of interventions to 6 weeks gestation (if applicable)

  3. Difference in ongoing pregnancy rate

    Evaluated by number of people with an ongoing pregnancy (gestational sac with fetal pole and cardiac activity seen on ultrasound at 12 weeks gestation), between intervention groups.

    Measured: Endpoint of interventions to 12 weeks gestation (if applicable)

  4. Change in uterine microbiota composition

    Evaluated by 16S rRNA sequencing of the uterine microbiota at baseline versus on the day of FET, and compared between experimental groups.

    Measured: Baseline, immediately after interventions

  5. Change in serum LPS

    Evaluated by changes in LPS-binding protein (LPS) at baseline versus on the day of FET, and compared between intervention groups.

    Measured: Baseline, immediately after interventions

  6. Change in intestinal permeability

    Evaluated by changes in untargeted peripheral blood metabolites at baseline versus on the day of FET, and compared between intervention groups.

    Measured: Baseline, immediately after interventions

  7. Change in peripheral cytokines

    Evaluated by changes in peripheral cytokines (TNF, IL-6, IL-8, IFNg - in pg/mL) at baseline versus on the day of FET, and compared between intervention groups.

    Measured: Baseline, immediately after interventions

  8. Change in urinary metabolites

    Evaluated by changes untargeted urinary metabolites at baseline versus on the day of FET, and compared between intervention groups. Nontargeted metabolic phenotyping of >100 urinary metabolites will be performed by multisegment injection capillary electrophoresis-mass spectrometry (MSI-CE-MS) as a high throughput platform to analyze metabolites. The fold change for each metabolite will be calculated between baseline vs. after interventions, and the fold changes will be compared between intervention groups.

    Measured: Baseline, immediately after interventions

Timeline

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

  1. First posted9 Jul 2021
  2. Study startJan 2023 (estimated)
  3. Primary completionJan 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Why it stopped: Change in departmental research focus.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04955574
Sponsor's protocol ID
JW-001
Status last verified
Jun 2023
First submitted
11 Jun 2021
Last updated
28 Jun 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eckert LO, Moore DE, Patton DL, Agnew KJ, Eschenbach DA. Relationship of vaginal bacteria and inflammation with conception and early pregnancy loss following in-vitro fertilization. Infect Dis Obstet Gynecol. 2003;11(1):11-7. doi: 10.1155/S1064744903000024.

    PubMed 12839628

  • Selman H, Mariani M, Barnocchi N, Mencacci A, Bistoni F, Arena S, Pizzasegale S, Brusco GF, Angelini A. Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome. J Assist Reprod Genet. 2007 Sep;24(9):395-9. doi: 10.1007/s10815-007-9146-5. Epub 2007 Jul 17.

    PubMed 17636439

  • Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazan J, Alonso R, Alama P, Remohi J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016 Dec;215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. Epub 2016 Oct 4.

    PubMed 27717732

  • Kyono K, Hashimoto T, Nagai Y, Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol. 2018 May 6;17(3):297-306. doi: 10.1002/rmb2.12105. eCollection 2018 Jul.

    PubMed 30013432

  • Fanchin R, Harmas A, Benaoudia F, Lundkvist U, Olivennes F, Frydman R. Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome. Fertil Steril. 1998 Nov;70(5):866-70. doi: 10.1016/s0015-0282(98)00277-5.

    PubMed 9806568

  • Egbase PE, Udo EE, Al-Sharhan M, Grudzinskas JG. Prophylactic antibiotics and endocervical microbial inoculation of the endometrium at embryo transfer. Lancet. 1999 Aug 21;354(9179):651-2. doi: 10.1016/s0140-6736(99)02415-0.

    PubMed 10466674

  • Moore DE, Soules MR, Klein NA, Fujimoto VY, Agnew KJ, Eschenbach DA. Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil Steril. 2000 Dec;74(6):1118-24. doi: 10.1016/s0015-0282(00)01624-1.

    PubMed 11119737

  • Brook N, Khalaf Y, Coomarasamy A, Edgeworth J, Braude P. A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer. Hum Reprod. 2006 Nov;21(11):2911-5. doi: 10.1093/humrep/del263. Epub 2006 Jul 10.

    PubMed 16832124

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SH-DS01 + Metronidazole in people with Unexplained Infertility and Endometriosis, run by McMaster University.

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 8 inclusion and 26 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: withdrawn, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Rate of study enrollment (time frame: Screening). The study lists 4 primary outcomes in all. 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 NCT04955574, which also lists 8 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 28 Jun 2023.

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