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

Sponsor

Peter Humaidan (Other)

Overall Status

Recruiting

CT.gov ID

NCT05166746

Collaborator

(none)

333

Enrollment

Locations

Arms

54.8

Anticipated Duration (Months)

83.3

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bacterial Vaginoses Infertility, Female	Drug: Clindamycin Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

333 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Moreover, an interim analysis will be performed by blinded outcomes assessors according to the primary outcome.

Primary Purpose:

Treatment

Official Title:

A Double-blind, Placebo-controlled Multicenter Trial on the Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota

Actual Study Start Date :

Dec 7, 2017

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: 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. Other Names: LACTIN-V
Active Comparator: 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.	Drug: 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. Other Names: LACTIN-V
Placebo Comparator: 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.	Other: 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

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: 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.

Other Names:

LACTIN-V

Active Comparator: 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.

Drug: 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.

Other Names:

LACTIN-V

Placebo Comparator: 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.

Other: 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

Outcome Measures

Primary Outcome Measures

Rate of clinical pregnancy per embryo transfer [7-9 weeks]
Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9

Secondary Outcome Measures

Cure of abnormal vaginal microbiota [1-2 months]
A vaginal swab and qPCR-validated diagnostics for abnormal vaginal microbiota
Live birth rate [25-42 weeks depending on pregnancy.]
The birth of a live born child after 25 gestational weeks.
Biochemical pregnancy [14 days gestation]
positive hCG blood test
Implantation rate [pregnancy scan at 7-9 weeks]
The number of embryos implanting
early miscarriage [14 days - 12 weeks gestation]
The loss of an hCG positive pregnancy
Number of late miscarriage [12 weeks gestation - to labour (i.e. not including still birth)]
The of pregnancy in late pregnancy
Number of preterm birth [prior to 37 gestational weeks]
birth of a liveborn
Birth weight [25-42 weeks gestation depending on pregnancy]
weight at birth

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 42 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Copenhagen University Hospital, Rigshospitalet	Copenhagen	Denmark	2100
2	Stork Fertility Clinic VivaNeo	Copenhagen	Denmark	2100
3	Hvidovre Hospital, The Fertility Clinic	Hvidovre	Denmark	2650
4	Fertility Clinic Skive, Skive Regional Hospital	Skive	Denmark	7800

Sponsors and Collaborators

Peter Humaidan

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Peter Humaidan, Professor, MD, Regionshospitalet Viborg, Skive

ClinicalTrials.gov Identifier:

NCT05166746

Other Study ID Numbers:

AVM_Lacto_2015/582

First Posted:

Dec 22, 2021

Last Update Posted:

Mar 10, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Clindamycin palmitate

Clindamycin phosphate

Study Results

No Results Posted as of Mar 10, 2022