Clinical trial NCT06007560: Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss
Official title: Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Recurrent Pregnancy Loss
Keywords: Natural Killer cells
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
First posted: 2023-08-23
Enrollment: 30
Sex: FEMALE
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: In 50% of women with recurrent pregnancy loss (RPL) miscarriages are unexplained, therefore no therapeutic intervention is possible. In a pilot study, women with unexplained RPL showed less endometrial NK cells (eNK) compared to women with a previously uncomplicated pregnancy. It is known that eNK cells are important for embryo implantation during early pregnancy. Investigators presume that high sympathetic activity in these women is related to eNK cell number, function and phenotype and that exercise is an effective intervention to lower sympathetic activity and to influence the immune system, as especially peripheral NK cells have been assumed to be responsive to physical training. The investigators hypothesize that moderate exercise can lower the adrenergic tone of the sympathetic nervous system hereby influencing endometrial NK cells in women with RPL and eventually pregnancy outcome.


Eligibility criteria: Inclusion Criteria:

* RPL defined as 2 or more unexplained pregnancy losses from the time of conception until 24 weeks of gestation, known cause for the miscarriages are the presence of thyroid abnormalities, anti-phospholipid syndrome, uterine malformation, and abnormal parental karyotype according to international guideline.
* Couples should not be aiming to conceive during the time course of the exercise intervention.

Exclusion Criteria:

* Age above 40 years
* BMI above 40
* Current use of immunosuppressive or biological drugs
* Current use of hormone conceptive
* HIV positivity
* Current or recent (\<2 weeks) symptomatic genital infection such as chlamydia, gonorroa, or pelvic inflammatory disease
* Pre-existent diabetes mellitus, autoimmune disease or overt cardiovascular disease
* Vaccination (i.e Covid) within 1 month prior to or during sampling and intervention
* New pregnancy at time of measurements, breastfeeding
* Current or recent (\<2-3 months ago) pregnancy
* (Physical) inabilities to follow moderate aerobe cycling training
* Participants who are not capable of signing the informed consent

Primary outcomes:
measure: CD56 endometrial NK cell frequency
timeFrame: 3 months
measure: CD56 endometrial NK cell function
timeFrame: 3 months
Secondary outcomes:
measure: CD56 endometrial NK cell phenotype
timeFrame: 3 months
measure: CD56 peripheral NK cell frequency
timeFrame: 3 months
measure: CD56 peripheral NK cell function
timeFrame: 3 months
measure: CD56 peripheral NK cell phenotype
timeFrame: 3 months
measure: Vaginal microbiome
timeFrame: 3 months
measure: Metabolic syndrome parameters I
timeFrame: 3 months
measure: Metabolic syndrome parameters II
timeFrame: 3 months
measure: Metabolic syndrome parameters III
timeFrame: 3 months
measure: Metabolic syndrome parameters IV
timeFrame: 3 months
measure: Metabolic syndrome parameters V
timeFrame: 3 months
measure: Sympathetic activity
timeFrame: 3 months
measure: Uterine blood flow
timeFrame: 3 months
measure: Physical fitness
timeFrame: 3 months
measure: Pregnancy rate and live birth rate after one year of intervention, higher rater indicate better outcome.
timeFrame: 3 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: Nijmegen
country: Netherlands
facility: Radboud UMC
Study officials:
affiliation: Radboud University Medical Center
name: Tess Meuleman
role: PRINCIPAL_INVESTIGATOR
References: