MenopauseMOSAICNCT07021664
Health, Imaging, and Cognition Across the Menopausal Transition
An observational study of Menopause, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
This observational cross-sectional study aims to better understand how the menopausal transition affects brain energy metabolism and cognition. Menopause, a natural stage in a woman's life, is typically divided into three phases: premenopause, perimenopause, and postmenopause. Read more about this study
- Who is it for?
- Ages 35 to 65 years, women only
- Conditions the study is for
- Menopause
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jul 2025to 1 Jul 2026
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Healthy individuals from the general population
Who may be able to join
- Able to read and speak French
- Capable of understanding and signing informed consent GROUP SPECIFIC INCLUSION CRITERIA Premenopause: • Women aged 35 to 55; No change in menstrual cycle regularity over the past 10 months (variation less than 7 days per cycle)
- Perimenopause: Women aged 40 to 60; Menstrual cycles varying by more than 7 days per cycle for at least 10 cycles, or no period for 3 to 11 months
- postmenopause: Women aged 45 to 65; No menstrual period for ≥ 12 months
Who cannot join
- Pregnancy, childbirth within the past 12 months, or breastfeeding
- Use of hormone replacement therapy or hormonal contraceptives in the past 6 months
- contraindications to MRI (e.g., presence of non-compatible metallic objects)
- Claustrophobia
- Type 1 diabetes
- Adherence to a ketogenic intervention (e.g., ketone supplements, intermittent fasting, ketogenic diet) in the past 3 months
Show all 12Show fewer
- Engaging in intense physical activity 5 times per week or more
- Any significant neurological disorder (e.g., dementia, brain tumor, seizure disorder, history of significant head trauma with persistent neurological deficits, known structural brain abnormalities)
- History of oophorectomy or hysterectomy
- Any significant psychiatric disorder (e.g., major depression within the past 2 years, bipolar disorder, schizophrenia)
- Systemic diseases or unstable/uncontrolled medical conditions (e.g., cardiovascular disease, uncontrolled diabetes, kidney or liver disorders)
- Any other condition that may interfere with participation, as judged by the study physician
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
Centre de recherche sur le Vieillissement
Sherbrooke, Quebec, J1H 4C4
Melanie Fortier, M.Sc., 8195758134, melanie.fortier2@usherbrooke.ca
About this study
Official title: Santé, Imagerie et Cognition à Travers la Transition ménopausique
This observational cross-sectional study aims to better understand how the menopausal transition affects brain energy metabolism and cognition. Menopause, a natural stage in a woman's life, is typically divided into three phases: premenopause, perimenopause, and postmenopause. This transition involves hormonal fluctuations and a decline in estrogen levels, which can impact physical, emotional, and cognitive well-being. Common symptoms include hot flashes, sleep disturbances, mood changes, and difficulties with memory and concentration.
Emerging evidence suggests that the decline in estrogen may impair how the brain uses glucose, its primary energy source. This reduction in glucose metabolism is thought to contribute to cognitive difficulties reported during midlife. In contrast, the brain's capacity to use ketones-alternative energy substrates produced during fasting or low-carbohydrate intake-appears preserved during aging and hormonal changes. Increasing circulating ketones may offer a promising strategy to support brain energy and cognitive function.
Read more
To explore these relationships, the study will employ advanced brain imaging (PET scans) to assess glucose and ketone uptake in the brain. Additional measures will include hormone levels, cognitive testing, continuous glucose monitoring, and MRI. PET tracers will also be used to evaluate estrogen receptor distribution, providing insight into how the brain responds to hormonal changes.
A total of 45 women aged 35-60 will be enrolled and categorized into three groups (15 per group): premenopause, perimenopause, and postmenopause. Each participant will attend four study visits that include questionnaires, blood tests, cognitive assessments, metabolic measurements, and imaging procedures.
The results may help identify early neurobiological and metabolic markers associated with the menopausal transition. These findings could inform new approaches to preserve brain health and prevent cognitive decline in aging women. Improving understanding of how the female brain adapts to hormonal shifts may ultimately support more targeted strategies for promoting healthy aging.
- Conditions
- Menopause
- Keywords
- menopause, cognition, metabolism, estrogen, ketone, PET scan, estrogen receptor
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| premenopause | Women between 35 and 55 years old who still have regular menstrual cycles, with no noticeable changes in the past 10 months. | |
| perimenopause | Women between 40 and 60 years old who have experienced changes in their menstrual cycles, such as irregular timing (varying by more than 7 days) for at least 10 cycles, or no period for 3 to 11 months. | |
| postmenopause | Women between 45 and 65 years old who have not had a menstrual period for 12 months or more. |
What is being measured
The primary outcome is the main question the study is designed to answer.
cerebral metabolic rates (μmol/100 g/min) measured by PET (11C-AcAc +18F-FDG)
Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST).Total Cerebral metabolic rates (μmol/100 g/min) (CMR tot= CMR acac + CMRglu)
Measured: 1 day at baseline
Tracer influx rates (k) measured by PET (11C-AcAc +18F-FDG)
Brain energy metabolism will be quantified using two PET tracers: 11C-acetoacetate (for ketone use) and 18F-fluorodeoxyglucose (for glucose use). This will allow comparison of brain fuel usage between three menopausal groups (PRE, PERI, POST). tracer influx rates (K values).
Measured: 1 day at baseline
Secondary outcomes (5)
Time-activity curves of the estrogen receptor in the brain (by 18F-4FMFES PET)
Time-activity curves of the estrogen recept will be measured using 18F-4FMFES PET express as SUV (Standardized Uptake Value)
Measured: 1 day at baseline
distribution volume ratio of the estrogen receptor in the brain (by 18F-4FMFES PET)
distribution volume ratio of the estrogen receptor will be measured by kinetic modelisation using 18F-4FMFES PET.
Measured: 1 day at baseline
Glucose variability (SD of glucose measured by continuous glucose monitoring)
Continuous glucose monitoring (CGM) will track glucose levels over several days. Glycemic variability will be assessed by the standard deviation of glucose values over the 5 days monitoring period. (mmol/L)
Measured: Over 5 days following sensor placement et stabilisation
Glucose average (mean of glucose measured by continuous glucose monitoring)
Continuous glucose monitoring (CGM) will track glucose levels over several days. Average glucose concentration over the monitoring period.(mmol/L)
Measured: Over 5 days following sensor placement et stabilisation
Time in range
Total minutes with glucose values within the standard glycemic range (3.9-10.0 mmol/L) over the 5 days monitoring period. (min)
Measured: Over 5 days following sensor placement et stabilisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2025
- Study start1 Jul 2025 (estimated)
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Nestlé Health Science
- Responsible party
- Sponsor
- Investigators
- Stephen Cunnane, Ph.D, Principal investigator, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07021664
- Sponsor's protocol ID
- 2025-58-28
- Acronym
- MOSAIC
- Status last verified
- May 2025
- First submitted
- 24 Apr 2025
- Last updated
- 15 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: There is no current plan to share individual participant data (IPD) with external researchers. While data reuse within the study team is permitted, external data sharing is subject to sponsor agreement and may be considered on a case-by-case basis in the future.
Publications
Andy C, Nerattini M, Jett S, Carlton C, Zarate C, Boneu C, Fauci F, Ajila T, Battista M, Pahlajani S, Christos P, Fink ME, Williams S, Brinton RD, Mosconi L. Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition. Front Endocrinol (Lausanne). 2024 Mar 4;15:1350318. doi: 10.3389/fendo.2024.1350318. eCollection 2024.
PubMed 38501109Castellano CA, Baillargeon JP, Nugent S, Tremblay S, Fortier M, Imbeault H, Duval J, Cunnane SC. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance. PLoS One. 2015 Dec 9;10(12):e0144116. doi: 10.1371/journal.pone.0144116. eCollection 2015.
PubMed 26650926Mosconi L, Nerattini M, Matthews DC, Jett S, Andy C, Williams S, Yepez CB, Zarate C, Carlton C, Fauci F, Ajila T, Pahlajani S, Andrews R, Pupi A, Ballon D, Kelly J, Osborne JR, Nehmeh S, Fink M, Berti V, Dyke JP, Brinton RD. In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology. Sci Rep. 2024 Jun 20;14(1):12680. doi: 10.1038/s41598-024-62820-7.
PubMed 38902275Paquette M, Phoenix S, Lavallee E, Rousseau JA, Guerin B, Turcotte EE, Lecomte R. Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using 18F-FES and 18F-4FMFES PET Imaging. Mol Imaging Biol. 2020 Oct;22(5):1403-1413. doi: 10.1007/s11307-020-01520-w. Epub 2020 Jul 22.
PubMed 32699974Arjmand S, Bender D, Jakobsen S, Wegener G, Landau AM. Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders. Biomolecules. 2023 Sep 18;13(9):1405. doi: 10.3390/biom13091405.
PubMed 37759805Fortier M, Castellano CA, St-Pierre V, Myette-Cote E, Langlois F, Roy M, Morin MC, Bocti C, Fulop T, Godin JP, Delannoy C, Cuenoud B, Cunnane SC. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimers Dement. 2021 Mar;17(3):543-552. doi: 10.1002/alz.12206. Epub 2020 Oct 26.
PubMed 33103819Fortier M, Castellano CA, Croteau E, Langlois F, Bocti C, St-Pierre V, Vandenberghe C, Bernier M, Roy M, Descoteaux M, Whittingstall K, Lepage M, Turcotte EE, Fulop T, Cunnane SC. A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Alzheimers Dement. 2019 May;15(5):625-634. doi: 10.1016/j.jalz.2018.12.017. Epub 2019 Apr 23.
PubMed 31027873Croteau E, Castellano CA, Richard MA, Fortier M, Nugent S, Lepage M, Duchesne S, Whittingstall K, Turcotte EE, Bocti C, Fulop T, Cunnane SC. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease. J Alzheimers Dis. 2018;64(2):551-561. doi: 10.3233/JAD-180202.
PubMed 29914035Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, Eckert A, Harvey J, Jeggo R, Jhamandas JH, Kann O, la Cour CM, Martin WF, Mithieux G, Moreira PI, Murphy MP, Nave KA, Nuriel T, Oliet SHR, Saudou F, Mattson MP, Swerdlow RH, Millan MJ. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. doi: 10.1038/s41573-020-0072-x. Epub 2020 Jul 24.
PubMed 32709961Mosconi L, Brinton RD. How would we combat menopause as an Alzheimer's risk factor? Expert Rev Neurother. 2018 Sep;18(9):689-691. doi: 10.1080/14737175.2018.1510320. Epub 2018 Aug 13. No abstract available.
PubMed 30091648Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Osorio RS, Connaughty C, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Swerdlow RH, Brinton RD. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery. PLoS One. 2017 Oct 10;12(10):e0185926. doi: 10.1371/journal.pone.0185926. eCollection 2017.
PubMed 29016679Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Varsavsky I, Osorio RS, Pupi A, Vallabhajosula S, Isaacson RS, de Leon MJ, Brinton RD. Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging. Neurology. 2017 Sep 26;89(13):1382-1390. doi: 10.1212/WNL.0000000000004425. Epub 2017 Aug 30.
PubMed 28855400Snyder HM, Asthana S, Bain L, Brinton R, Craft S, Dubal DB, Espeland MA, Gatz M, Mielke MM, Raber J, Rapp PR, Yaffe K, Carrillo MC. Sex biology contributions to vulnerability to Alzheimer's disease: A think tank convened by the Women's Alzheimer's Research Initiative. Alzheimers Dement. 2016 Nov;12(11):1186-1196. doi: 10.1016/j.jalz.2016.08.004. Epub 2016 Sep 27.
PubMed 27692800Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, Salamone L, Stellato R. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol. 2000 Sep 1;152(5):463-73. doi: 10.1093/aje/152.5.463.
PubMed 10981461Delanerolle G, Phiri P, Elneil S, Talaulikar V, Eleje GU, Kareem R, Shetty A, Saraswath L, Kurmi O, Benetti-Pinto CL, Muhammad I, Rathnayake N, Toh TH, Aggarwal IM, Shi JQ, Taylor J, Riach K, Potocnik K, Litchfield I, Kemp HF, Briggs P; MARIE collaborative. Menopause: a global health and wellbeing issue that needs urgent attention. Lancet Glob Health. 2025 Feb;13(2):e196-e198. doi: 10.1016/S2214-109X(24)00528-X. Epub 2024 Dec 18. No abstract available.
PubMed 39708829