Probiotic Intake and Perimenopausal Psychological Assessments

NCT07590999 | Recruiting

• 1 other identifier: PIPPA Study (735575)
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Recent evidence suggests multi-strain probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum have been found to enhance emotional processing and reduce salience to negative cues in studies involving people with mood disorders, as well as improve cognitive functions, such as memory and concentration, in healthy participants. By administering computer-based tasks, questionnaires and checking biological measures (cortisol, immune markers, blood metabolites, gut microbiota) using blood and faecal samples, this experimental medicine study aims to investigate whether a probiotic supplement has an effect on emotional processing and cognition in perimenopausal women. We also aim to study changes in gut bacteria from stool samples before and after taking the supplement to see if any microbiome changes are associated with any effects in emotional processing, cognitive function, and biological markers.

Conditions

Perimenopause; Perimenopause-Related Depression; Perimenopausal Women; Emotional Processing and Cognitive Function in Perimenopausal Women Experiencing Cognitive Perturbations

Keywords

perimenopause; menopause; gut microbiome and perimenopause; cognition and perimenopause; emotional processing and perimenopause; mood and perimenopause; gut microbiome and cognition; probiotics; probiotic; gut microbiome

Outcome Measures

Primary Outcomes (1)

• Facial Expression Recognition Task (FERT)

  Accuracy, reaction time and misclassifications on the FERT compared between probiotic and placebo groups.

  End of the 60-day intervention

Secondary Outcomes (11)

• Emotional Categorisation Task

  End of the 60-day intervention

• Emotional word recall/recognition task

  End of the 60-day intervention

• Digit Span Task

  End of the 60-day intervention

• Emotional Go/No-Go (EGNG)

  Post-intervention (end of 60-day intervention)

• Probabilistic Reversal Learning (PRL) Task

  Post-intervention (end of 60-day intervention)

Other Outcomes (6)

• Subjective measures of affective state

  Baseline, Day 14, Day 30, Day 44, Day 60

• Subjective measures of mood

  Baseline, Day 14, Day 30, Day 44, Day 60

• Subjective measures of menopausal symptom severity

  Baseline, Day 14, Day 30, Day 44, Day 60

Study Arms (2)

Patient Group

PLACEBO COMPARATOR

Participants randomised to the Placebo condition will be taking four microcrystalline cellulose powder placebo capsules daily for 60 days.

Dietary Supplement: Placebo

Interventional/Treatment

EXPERIMENTAL

Participants randomised to the Probiotic condition will be taking four multi-strain probiotic capsules daily for 60 days.

Dietary Supplement: Multi-strain probiotic

Interventions

Multi-strain probiotic DIETARY_SUPPLEMENT

A commercially available probiotic known to support gut health and is generally well-tolerated.

Interventional/Treatment

Placebo DIETARY_SUPPLEMENT

A microcrystalline cellulose-based capsule.

Patient Group

Eligibility Criteria

• Age: 45 Years - 60 Years
• Gender Eligibility Details: Biological females who identify as females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female at birth
• You are aged 45-60 years and in perimenopause (determined by changes in menstrual bleeding patterns (such as changes in cycle length of 7 days or longer in either direction from what is normal for you), AND vasomotor symptoms (e.g., hot flushes and sweats) AND mild to moderate mood or cognitive disturbances, or joint and muscle pain over the previous 12 months)
• You are willing and able to give informed consent for participation in the study
• You are sufficiently fluent in English to understand and complete tasks
• You are at least 12 months post-natal
• Willing to withhold from having grapefruit juice

You may not qualify if:

• Currently receive or seek treatment for any mental health condition
• Have a BMI \>=30 OR \<=18.5
• Have lost or gained more than 10% of body weight in a short period (e.g., 6 months), as this can affect mood and cognition
• Currently using hormonal contraception or have used hormonal contraception in the last 6 months
• Have had gender reassignment surgery or gender-affirming hormone therapy
• Had a head injury causing concussion or unconsciousness in the past 6 months
• Participated in other studies that may influence mood, cognition, or gut health in the last three months
• Are currently diagnosed with and/or treated for psychiatric or neurological disorders
• Are on perimenopausal hormone replacement therapy (HRT) (e.g., estrogen, progesterone, testosterone) or other hormone-modulating medications (e.g., GLP-1 agonists, thyroxine replacement), as these can impact mood and cognitive functions
• Currently use statins or have used statins in the last 6 months, as these may impact mood and cognitive functions
• Participated in any other study with the same tasks in the last year
• Currently use medications that influence cognition or mood, such as antidepressants, anxiolytics, antipsychotics, stimulants, mood-stabilizers, or cognitive-enhancing drugs
• Have chronic or severe gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, celiac disease, or severe acid reflux; treatment with e.g., corticosteroids, antacids), as these conditions and treatments can affect the gut microbiota and immune responses differently from healthy individuals
• Have a compromised immune system
• Currently smoke, vape, or use any other nicotine products

Sponsors & Collaborators

• University of Oxford: lead
• ADM Protexin: collaborator

Study Sites (1)

University of Oxford, Department of Psychiatry

Oxford, England, OX3 7JX, United Kingdom

RECRUITING

Related Publications (10)

• Weber MT, Rubin LH, Maki PM. Cognition in perimenopause: the effect of transition stage. Menopause. 2013 May;20(5):511-7. doi: 10.1097/gme.0b013e31827655e5.

  PMID: 23615642 BACKGROUND

• Weber MT, Mapstone M, Staskiewicz J, Maki PM. Reconciling subjective memory complaints with objective memory performance in the menopausal transition. Menopause. 2012 Jul;19(7):735-41. doi: 10.1097/gme.0b013e318241fd22.

  PMID: 22415562 BACKGROUND

• Ruiz-Gonzalez C, Cardona D, Rueda-Ruzafa L, Rodriguez-Arrastia M, Ropero-Padilla C, Roman P. Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double-Blind Randomized Placebo-Controlled Crossover Trial. Probiotics Antimicrob Proteins. 2025 Oct;17(5):3525-3537. doi: 10.1007/s12602-024-10315-2. Epub 2024 Jun 27.

  PMID: 38935259 BACKGROUND

• Nikolova VL, Cleare AJ, Young AH, Stone JM. Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Aug 1;80(8):842-847. doi: 10.1001/jamapsychiatry.2023.1817.

  PMID: 37314797 BACKGROUND

• Maki PM, Kornstein SG, Joffe H, Bromberger JT, Freeman EW, Athappilly G, Bobo WV, Rubin LH, Koleva HK, Cohen LS, Soares CN; Board of Trustees for The North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause. 2018 Oct;25(10):1069-1085. doi: 10.1097/GME.0000000000001174.

  PMID: 30179986 BACKGROUND

• Conde DM, Verdade RC, Valadares ALR, Mella LFB, Pedro AO, Costa-Paiva L. Menopause and cognitive impairment: A narrative review of current knowledge. World J Psychiatry. 2021 Aug 19;11(8):412-428. doi: 10.5498/wjp.v11.i8.412. eCollection 2021 Aug 19.

  PMID: 34513605 BACKGROUND

• Bromberger JT, Epperson CN. Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstet Gynecol Clin North Am. 2018 Dec;45(4):663-678. doi: 10.1016/j.ogc.2018.07.007. Epub 2018 Oct 25.

  PMID: 30401549 BACKGROUND

• Berent-Spillson A, Marsh C, Persad C, Randolph J, Zubieta JK, Smith Y. Metabolic and hormone influences on emotion processing during menopause. Psychoneuroendocrinology. 2017 Feb;76:218-225. doi: 10.1016/j.psyneuen.2016.08.026. Epub 2016 Sep 5.

  PMID: 27622993 BACKGROUND

• Baiao R, Capitao LP, Higgins C, Browning M, Harmer CJ, Burnet PWJ. Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study. Psychol Med. 2023 Jun;53(8):3437-3447. doi: 10.1017/S003329172100550X. Epub 2022 Feb 7.

  PMID: 35129111 BACKGROUND

• Appleton J. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integr Med (Encinitas). 2018 Aug;17(4):28-32.

  PMID: 31043907 BACKGROUND

Study Officials

• Phil Burnet, Professor

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phil Burnet, Professor

CONTACT

+44 1865 618327; phil.burnet@psych.ox.ac.uk

Susannah Murphy, Professor

CONTACT

+44 1865 618313; susannah.murphy@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: A researcher, not involved in the study, will generate the randomisation code using an online tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists). Participants will be stratified by BMI, and participants will receive identical daily capsules, either probiotic or placebo. Treatment allocation will be documented on a Randomisation List, updated for each participant, and stored securely. Participants will remain unaware of their group allocation to ensure blinding.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized into one of two groups, each undergoing 60 days of either 1) Placebo or 2) Probiotic.

Study Record Dates

• First Submitted: March 12, 2026
• First Posted: May 15, 2026
• Study Start: November 12, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)