Late-perimenopause, Menopause, Perimenopause
Conditions
Keywords
Peri-menopause, menopause, intermittent fasting, low glycaemic-index diet, women, time-restricted eating, biological ageing, metabolic markers, cognitive function, cognition, tender joints, swollen joints, nutrition, microbiome, Mediterranean diet, GlycanAge, randomized controlled trial, BDNF, insulin resistance, middle-aged, global health
Brief summary
The goal of this randomised controlled trial is to investigate whether Time-Restricted Eating (TRE) combined with a Low Glycaemic Index Mediterranean Diet can improve cognitive function, metabolic health, and biological ageing in late perimenopausal and menopausal women aged 45-75 years with a BMI ≥23 kg/m². It will consist of a 12-week intervention followed by a 12 week follow-up period. Researchers will compare a group following the 16:8 time-restricted eating schedule and Low Glycaemic Index Mediterranean Diet to a control group (waiting list) receiving no dietary or meal-timing instructions to determine if these dietary strategies influence cognitive function, assessed via brain-derived neurotropic factor (BDNF) and cognitive function tests, metabolic outcomes, biological age, the gut microbiome, tender and swollen joint count and global health. Participants will: Follow a 16:8 time-restricted eating schedule (eating within an 8-hour window and fasting for 16 hours) if assigned to the intervention group. Adhere to a tailored Low Glycaemic Index Mediterranean Diet and track meals using the Nutrium app. Attend study visits at the University of Nicosia at Week 0, Week 12, and Week 24 for various assessments. Provide biological samples, including blood samples at five specific intervals and stool samples at Week 0 and Week 12. Complete multiple questionnaires regarding diet, lifestyle, sleep quality, physical activity, tender and swollen joints, and quality of life. Undergo physical and cognitive assessments, such as CNS Vital Signs tests, blood pressure measurements, and body composition analysis. The two groups will be compared to understand if the intervention improves outcomes and can thus be applied in this population group.
Detailed description
This randomized controlled trial will run over a period of 24 weeks (6 months) and will be divided into two main phases: a 12-week intervention phase followed by a 12- week follow-up phase designed to assess long-term adherence and health outcomes. The participants will be randomized to one of two groups: the intervention group of a Time-Restricted Eating combined with a Low Glycaemic Index diet (TRE-LGI) group, and the control group which will not receive any dietary intervention. During the intervention phase (Week 0 to Week 12), participants randomized to the TRE-LGI group will follow a structured eating plan. They will be instructed to consume all their meals within an 8-hour eating window each day and adhere to a low glycaemic index Mediterranean-style diet. Participants randomized to the control group will not receive any dietary intervention but will continue to be monitored for study purposes. Assessments will be conducted at three time points during this phase. At baseline (Week 0), participants will complete a full set of evaluations, including the online Computerised Neurocognitive Testing tool CNS Vital Signs, metabolic markers (insulin sensitivity, and lipid profiles, C-reactive protein (CRP), BDNF assessment using Enzyme-Linked Immunosorbent Assay (ELISA) Test, biological ageing assessment using the N-glycome analysis (GlycanAge test), gut microbiome analysis from stool samples, body composition, blood pressure, waist circumference, sleep quality using the Pittsburgh Sleep Quality Index (PSQI), physical activity using the International Physical Activity Questionnaire-Short Form IPAQ-SF, tender and swollen joint count and Global Health using the PROMIS® Scale v1.2 - Global Health. At Week 6, only the N-glycome composition analysis (GlycanAge) will be repeated to monitor changes in biological ageing. At Week 12, all baseline assessments will be repeated to measure the effects of the intervention. The follow-up phase, spanning from week 12-24, will focus on evaluating the participants' ability to sustain the dietary practices achieved during the intervention period without receiving further active dietary guidance. Monitoring will continue to measure the longer-term effects on cognitive, metabolic, and biological health outcomes. At Week 18, participants will undergo N-glycome composition analysis (GlycanAge) to continue monitoring biological ageing. At Week 24, a final comprehensive assessment will be conducted, including cognitive function (CNS Vital Signs), BDNF Test, N-glycome analysis, body composition using BIA, BMI, blood pressure, waist circumference, and sleep quality (PSQI), physical activity (IPAQ-SF), tender and swollen joint count, and Global Health PROMIS questionnaire. Participants in the control group will complete the same assessments at each scheduled time point, allowing for direct comparisons; however, they will not undergo any dietary intervention throughout the study.
Interventions
OTHERTime-Restricted Low-Glycaemic Index Diet
The combination of a 16:8 Time-Restricted eating period with a low glycaemic index Mediterranean diet
Sponsors
University of Nicosia
Digital Diet Clinic Ltd
GENOS LIMITED
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Women in late perimenopausal or menopausal status Note: Late perimenopause is defined as two or more skipped cycles and at least 60 days of amenorrhea. Recent blood tests showing elevated FSH levels support eligibility for late perimenopause. Menopause is defined as 12 consecutive months without a menstrual cycle. * BMI ≥23 kg/m2 * Age 45-75 years old * If using any medication, the dose should be stable for the previous 12 months * Able to use technology and follow the dietary plan
Exclusion criteria
* Diagnosis of mild cognitive impairment (MCI) or Alzheimer's disease (AD). Note: (Self-reported memory complaints are allowed). * On hormone replacement therapy (HRT) * Medical conditions that significantly affect cognitive or metabolic function including diagnosis of type 1 diabetes, severe metabolic disorders, cardiovascular disease, or neurodegenerative conditions, diagnosed eating disorders or severe mental health conditions. * Currently enrolled in another intervention. * Severe food allergies or dietary restrictions that would prevent adherence to the study diet. * History of substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain-derived neurotrophic factor concentration | Week 0 and Week 12 for the intervention period and Week 24 for the follow-up period | Changes between the intervention and control group in the concentration of brain-derived neurotrophic factor assessed by Enzyme-linked Immunosorbent Assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive function | Week 0 and Week 12 for the intervention period and Week 24 for the follow-up period | Cognitive function using CNS Vital Signs assessments, including visual, verbal and composite memory, reaction time, executive function, complex attention and cognitive flexibility |
| Insulin resistance | Week 0 and Week 12 for the intervention period | Fasting glucose and insulin to assess insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). |
| Lipid profile | Week 0 and Week 12 for the intervention period | Total cholesterol, LDL and HDL cholesterol, Triglyceride concentration, the triglyceride-to-HDL (TG/HDL) ratio will be calculated as a predictive marker for cardiovascular risk |
| C-reactive protein (CRP) | Week 0 and Week 12 for the intervention period | CRP concentration to assess inflammation |
| IgG N-glycome composition analysis to assess GlycanAge | The test will be conducted at Week 0, 6, 12, 18, and 24 to monitor progressive changes in biological ageing throughout the 6-month study period. | The IgG N-glycome composition analysis will be used to measure biological ageing and systemic inflammation by analysing glycans attached to immunoglobulin G (IgG) antibodies in participants' blood samples using high-performance liquid chromatography (HPLC). |
| Anthropometric measurements: Body weight, height, and calculation of the Body Mass Index | Week 0 and weekly thereafter until Week 24 for body weight and BMI, Week 0: Body height | Body weight will be measured using minimal clothing. Height will be measured using a standard stadiometer. BMI will be calculated as weight in kg divided by height in metres squared |
| Body composition analysis using Bioelectrical Impedance Analysis | Week 0 and Week 12 for the intervention phase and Week 24 for the follow-up phase | Body composition analysis using Bioelectrical Impedance Analysis in the fasted state to assess % body fat, body fat mass, fat-free mass, skeletal muscle mass and visceral fat |
| Gut microbiome | Week 0 and Week 12 for the intervention period | Gut microbiome will be assessed by performing phyla-level PCR analysis on the stool sample |
| Blood pressure | Week 0 and Week 12 of the intervention period and Week 24 of the follow-up period | Blood pressure will be assessed using standard methods |
| Sleep duration and quality | Week 0 and Week 12 for the intervention period and Week 24 for the follow-up period | Subjective assessment of sleep duration and quality using the Pittsburgh Sleep Quality Index (PSQI) |
| Global Health | Week 0 and Week 12 for the intervention period and Week 24 for the follow-up period | Global Health will be assessed using the PROMIS® Scale v1.2 - Global Health which evaluates key domains including global physical health, global mental health, physical function, fatigue, pain interference, emotional distress, social health, and quality of life through Likert-scale items. |
| Tender and swollen joint count | Week 0 and Week 12 for the intervention period and Week 24 for the follow-up period | The participant's number of tender and swollen joints will be self-assessed by providing a diagram to the participant, where they can mark any tender and/or swollen joints. |
Countries
Croatia, Cyprus
Contacts
CONTACTElena Philippou, PhD
CONTACTFrancesco Colelli, MSc
PRINCIPAL_INVESTIGATORElena Philippou, PhD
University of Nicosia
Outcome results
None listed