The Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota

NCT ID: NCT05166746

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 333 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2023-10-01

Brief Summary

Study question: Does antibiotic alone or in combination with live biotherapeutic treatment of an abnormal vaginal microbiota improve the reproductive outcomes of IVF couples?

Study hypothesis:

The investigator hypothesize that treatment of the reproductive tract pathogens and restoration of vaginal Lactobacillus will improve the reproductive outcomes of IVF patients.

What is known already? Ultra-deep sequencing methods enable the refinement of reproductive tract microbiology in infertile patients. A recent meta-analysis reported that 19% of infertile patients had abnormal vaginal microbiota Moreover, someone have detected the presence of a Gardnerella (G.) vaginalis dominated endometrial biofilm in 50% of non-infertile patients with abnormal vaginal microbiota undergoing curettage; thus the treatment of such an endometrial biofilm might play an important role for the endometrial receptivity and subsequently the clinical pregnancy rate.

Pilot study: In a recent pilot study it was observed that an abnormal vaginal microbiota negatively affects the clinical pregnancy rate in IVF patients. In this study the prevalence of abnormal vaginal microbiota was 28% (36/130) and only 9% of patients with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (p=0.004). This association remained significant in an adjusted analysis. Furthermore, the invetigators have preliminary results demonstrating that vaginal bacteria such as G. vaginalis can be found in the endometrium of IVF patients, which is also supported by recent publications

What is the novelty of this study? To the investigators knowledge, no previous treatment study of abnormal reproductive tract microbiota has been performed in IVF patients; this relatively small intervention holds the potential to increase the baby-take-home rate after IVF treatment.

Conditions

Bacterial Vaginoses; Infertility, Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Clindamycin + LACTIN-V (L.crispatus)

Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.

Group Type: ACTIVE_COMPARATOR

Clindamycin

Intervention Type: DRUG

Oral clindamycin 300mg/2xdaily in 7 days. LACTIN-V applicators 1x at night in 7 days, then 2xper week at night for 7 weeks.

Clindamycin + placebo LACTIN-V

Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V placebo (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.

Group Type: ACTIVE_COMPARATOR

Clindamycin

Intervention Type: DRUG

Oral clindamycin 300mg/2xdaily in 7 days. LACTIN-V applicators 1x at night in 7 days, then 2xper week at night for 7 weeks.

Placebo clindamycin + placebo LACTIN-V

Matching clindamycin placebo 2 times per day for 7 days followed by LACTIN-V placebo (Osel Inc.) until completion of the clinical pregnancy scan at week 7-9.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

The Clindamycin placebo appear identical to active clindamycin by filling capsules with Mannitolium.

The LACTIN-V placebo product has no intrinsic effect and is used to study the effect of the therapeutically active product. It is supplied as a pre-filled vaginal applicator packaged under nitrogen gas with one desiccant packet (0.25 g) in a sealed foil pouch. Each applicator contains 200 mg of LACTIN-V placebo powder containing the inactive ingredients of the LACTIN-V drug product, but not Lactobacillus crispatus CTV-05 (CTV-05), the active ingedient. The excipients used in the manufacture of LACTIN-V placebo are identical to those in the LACTIN-V drug product. Each placebo applicator contains the following constituents: maltodextrin, trehalose, xylitol, colloidal silicon dioxide, and sodium ascorbate

Interventions

Clindamycin

Oral clindamycin 300mg/2xdaily in 7 days. LACTIN-V applicators 1x at night in 7 days, then 2xper week at night for 7 weeks.

Intervention Type: DRUG

Placebo

The Clindamycin placebo appear identical to active clindamycin by filling capsules with Mannitolium.

The LACTIN-V placebo product has no intrinsic effect and is used to study the effect of the therapeutically active product. It is supplied as a pre-filled vaginal applicator packaged under nitrogen gas with one desiccant packet (0.25 g) in a sealed foil pouch. Each applicator contains 200 mg of LACTIN-V placebo powder containing the inactive ingredients of the LACTIN-V drug product, but not Lactobacillus crispatus CTV-05 (CTV-05), the active ingedient. The excipients used in the manufacture of LACTIN-V placebo are identical to those in the LACTIN-V drug product. Each placebo applicator contains the following constituents: maltodextrin, trehalose, xylitol, colloidal silicon dioxide, and sodium ascorbate

Intervention Type: OTHER

Other Intervention Names

LACTIN-V

Eligibility Criteria

Inclusion Criteria

• Abnormal vaginal microbiota.
• The screening swab should be repeated if more than 3 months old.
• HIV, Hepatitis B or C positivity.
• First, second or third IVF stimulation cycle or embryo transfer therefrom.
• BMI<35
• Written informed consent.

Exclusion Criteria

• Known or suspected hypersensitivity to clindamycin.
• HPV CIN 2 or higher.
• Former or current inflammatory bowel disease
• Severe concomitant disease, including diabetes.
• MAX 2 embryos may be transferred
• Artificial heart valve
• Intrauterine malformations with operation indication as determined by treating physician (Polyps, Septum, fibroma)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Peter Humaidan

OTHER

Sponsor Role: lead

Responsible Party

Peter Humaidan

Professor, MD

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Stork Fertility Clinic VivaNeo

Copenhagen, , Denmark

Site Status: RECRUITING

Hvidovre Hospital, The Fertility Clinic

Hvidovre, , Denmark

Site Status: RECRUITING

Fertility Clinic Skive, Skive Regional Hospital

Skive, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Thor Haahr, MD

Role: CONTACT

thohaa@rm.dk

+4527885402

Facility Contacts

Henriette Svarre, MD

Role: primary

Henriette.Svarre.Nielsen@regionh.dk

Vibeke Hartvig, MD

Role: primary

vibeke.hartvig@storkklinik.dk

Nina La Cour Freiesleben, MD

Role: primary

nina.la.cour.freiesleben@regionh.dk

Thor Haahr, MD

Role: primary

thorhaahr@hotmail.com

Other Identifiers

AVM_Lacto_2015/582

Identifier Type: -

Identifier Source: org_study_id