- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06213428
Effects of Probiotics on Synaptic Plasticity During the Menstrual Cycle
Investigating the Effects of Probiotics on Synaptic Plasticity in the Follicular and Luteal Phases of the Menstrual Cycle
Modulation of our gut microbiota through probiotics, can improve our emotional state, decrease pain sensitivity, improve cognitive processes, increase neurotransmitter levels and alter functional connectivity. In addition, probiotics regulate estrogen levels. Estrogen levels have been recognized to influence the gut microbiota, impact neural activity, memory, and cognition.
This study aims 1) to determine whether probiotics can increase the propensity for synaptic plasticity in females and 2) to determine if there are differences in the propensity for plasticity depending on the phase of the menstrual cycle.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The human gastrointestinal (GI) tract is comprised of trillions of bacterial strains. Recent work has focused on investigating the influence of the gut microbiota on the processing and function of our brain; this is known as the 'gut-brain axis'. Our gut microbiota can be altered through diet, antibiotics, prebiotics and probiotics (Hemarajata et al., 2013). Probiotics are live microorganisms, which when delivered in adequate amounts, can offer beneficial health outcomes to the host (Hill et al., 2014). Modulation of our gut microbiota through probiotics, can improve our emotional state (Bagga et al., 2018; Messaoudi et al., 2011; Tillisch et al., 2013), decrease pain sensitivity (Weizman et al., 2016), improve cognitive processes (Chung et al., 2014; Kim et al., 2020), increase neurotransmitter levels (Mittal et al., 2017) and alter functional connectivity (Rode et al., 2022; Bagga et al., 2019). In addition, probiotics regulate estrogen levels (Guo et al., 2016; Urbaniak et al., 2016).
Estrogen levels have been recognized to influence the gut microbiota. The gut produces β-glucuronidases which is the enzyme required to breakdown conjugated estrogen into its active form (Dabek et al., 2008; Ervin et al., 2019). Low β-glucuronidases production occur in the presence of diminished bacterial diversity levels in the gut. The consequence of the low β-glucuronidases is a reduction in active forms of estrogen (Siddiqui et al., 2022; Pugh et al., 2021; Kwa et al., 2016, Baker et al., 2017). Further, gastrointestinal symptoms increase during menstruation (Pugh et al., 2021). Last, irritable bowel syndrome is more prevalent in females, indicating a possible role of sex hormones in relation to the gut microbiome (Pugh et al., 2021).
Estrogen has been found to impact neural activity, memory, and cognition (Inghilleri et al., 2004; Luine 2014). EEG brain activity was collected from women in their follicular and luteal phase (Brotzner et al., 2014). When estrogen levels were highest, individual alpha frequency oscillations (IAF) were lowest (Brotzner et al., 2014), the latter is associated with reduced cognition and working memory (Li et al., 2023). In addition, estrogen was found to reduce the firing threshold in some neurons which can promote excitability in the cortex (Gregory et al., 2019). Conversely, high progesterone levels are known to increase GABA activity which reduces neural activity (Guennoun et al., 2015). Furthermore, a 5Hz repetitive transcranial magnetic stimulation (rTMS) protocol was delivered over the motor cortex during the early and late follicular phase (Inghilleri et al., 2004). Corticospinal activity was increased when estradiol levels were highest (Inghilleri et al., 2004) showing the association between estradiol and synaptic plasticity.
Collectively, the literature suggests that women may have a reduced capacity for synaptic plasticity during the luteal phase when estradiol levels are low. Introducing a probiotic will increase β-glucuronidases which leads to greater availability of circulating estrogen which should promote synaptic plasticity. It is hypothesized that increases in synaptic plasticity will occur in the follicular and luteal phase in the presence of probiotics. This study aims 1) to determine whether probiotics can increase the propensity for synaptic plasticity in females and 2) to determine if there are differences in the propensity for plasticity depending on the phase of the menstrual cycle.
Methods:
Participants will be randomized into Group A or Group B. Twenty participants will be in Group A and 20 participants will be in group B. If randomized to Group A, all visits will be conducted between day 6-9 (mid-follicular phase) when estradiol levels are highest. If randomized to Group B, all visits will be conducted during day 19-23 (mid-luteal phase) when progesterone levels are highest. This will be a randomized, crossover, double-masked study whereby participants will receive both real probiotic and placebo probiotic for 28 days. Assessments will be acquired during four visits (Before and after each intervention, separated by a 28 day washout). The McMaster University Medical Centre (MUMC) pharmacy will be responsible for the preparation of the blinded probiotic kits and randomization schedule. The probiotic used will be a commercially available product called Progressive Perfect Probiotic (https://www.progressivenutritional.com/products/perfect-probiotic-120-billion).
The following dependent measures will be used: Active motor threshold, Resting motor threshold, short interval intracortical inhibition, motor evoked potentials.
These measures will be taken before and after a synaptic plasticity inducing protocol
To assess synaptic plasticity, repetitive TMS will be performed using a 70mm inner diameter figure-of-eight coil with a Magstim Super Rapid2 Plus Stimulator (Magstim, Whitland, UK). Biphasic magnetic pulses will be delivered over the primary motor area of the dominant hemisphere to find the optimal position for eliciting a MEP in the contralateral APB muscle. Intermittent theta burst stimulation (iTBS) protocol will be delivered using biphasic pulses in burst of three pulses delivered in 6Hz trains that will last 2s, this will be followed by 8s with no pulse delivered. iTBS will be repeated for a total of 612 pulses at 80% of AMT (Fassett et al., 2017).
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Aimee J Nelson, PhD
- Phone Number: 28053 9055259140
- Email: nelsonaj@mcmaster.ca
Study Contact Backup
- Name: Faith C Adams, BSc
- Email: adamsf4@mcmaster.ca
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8S 4K1
- McMaster Unviersity
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- right handed, females between 18-35 years old with a regular menstrual cycle (approximately 26-30 days)
Exclusion Criteria:
- contradictions to TMS
- contradictions to probiotic
- Females who use hormone altering devices (i.e. oral contraceptives)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Active: Probiotic
Progressive Perfect Probiotic 120 Billion CFU containing the following strains will be used: Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bifidobacterium animalis subsp.lactis, Bifidobacterium breve, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus reuteri, Bifidobacterium bifidum, Bifidobacterium longum subsp. Longum. Participants will be required to take one capsule a day, for 28 days. |
Participants will be administered an active probiotic for 28 days.
Participants will be blinded as to what intervention they are experiencing.
|
Placebo Comparator: Placebo Probiotic
A placebo that is identical in capsule size and colour to the active probiotic capsule will be used.
This will ensure participants and experimenters are masked during each intervention period.
Participants will be required to take one capsule a day for 28 days.
|
Participants will be administered a placebo for 28 days.
Participants will be blinded as to what intervention they are experiencing.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change Motor Evoked Potentials (MEPs)
Time Frame: Immediately before intervention, immediately following 4 week intervention
|
Change in MEPs using TMS
|
Immediately before intervention, immediately following 4 week intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Short Interval intracortical inhibition (SICI)
Time Frame: Immediately before intervention, immediately following 4 week intervention
|
Changes in SICI Using TMS
|
Immediately before intervention, immediately following 4 week intervention
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 16602
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Women's Health
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São PauloCompleted
-
Turtle Health, Inc.Completed
-
US Department of Veterans AffairsCompletedWomen's HealthUnited States
-
Georgetown UniversityUnited States Agency for International Development (USAID)Completed
-
University of TorontoCompleted
-
RTI InternationalEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsCompleted
-
LirioRochester Regional HealthCompletedHealth Behavior | Women's Health | Prevention | Annual Visit | Well VisitUnited States
-
Johns Hopkins UniversityZanvyl and Isabelle Krieger Fund; Abell FoundationCompletedWomen's Health | Preconception CareUnited States
-
Amasya UniversityNot yet recruitingPregnant Women | Women's Health | Childbirth
-
University of Illinois at ChicagoAgency for Healthcare Research and Quality (AHRQ)CompletedContraception Behavior | Women's Health | Primary Health Care | Postpartum PeriodUnited States
Clinical Trials on Progressive Perfect Probiotic
-
Seoul National University Bundang HospitalRecruitingNeovascular Age-related Macular DegenerationKorea, Republic of
-
University of California, San DiegoDuke University; University of California, San Francisco; Harvard University; Mount... and other collaboratorsCompleted
-
Charite University, Berlin, GermanyCompletedOutcomes | Body TemperatureGermany
-
Medical University of South CarolinaWithdrawnCataract ExtractionUnited States
-
Cedars-Sinai Medical CenterStryker NordicCompletedTibial Fractures | Nonunion of Fracture | Femur Fracture | Tibia Fracture | Nonunion of Fracture of Tibia | Nonunion of Fracture of Femur (Diagnosis)United States
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityCompleted
-
Tufts Medical CenterDialysis Clinic, Inc.Terminated
-
Lazarski UniversityThe Cleveland Clinic; Wroclaw Medical UniversityCompletedUltrasonography | Optic Nerve Sheath DiameterPoland
-
Ataturk UniversityCompletedStress | Anxiety | Nursing Students | Relaxation ProgramTurkey
-
Leiden University Medical CenterRecruitingSmoking | Physical InactivityNetherlands