Gut -Microbiota, Mood, Perimenopause, Perimenopause-Related Depression, Quality of Life, Sleep
Conditions
Keywords
phytochemical, fibre, mood, sleep, quality of life, gut
Brief summary
This is a clinical trial aimed to investigate if a novel phytochemical and fibre-rich snack can improve perimenopausal symptoms and well-being in perimenopausal women aged 40-55 and not on hormone replacement therapy. Hypothesis: The investigators hypothesise that the phytochemical and fibre-rich snack will improve perimenopausal symptoms via a gut microbiota mediated mechanism. Main research questions: Does eating the snack every day lower menopause symptoms such as hot flushes, night sweats, mood changes, and sleep problems? Does the snack improve mood, stress, anxiety, sleep, and overall quality of life? Does the snack improve the balance of bacteria in the gut, and could this be part of how it helps symptoms?
Detailed description
This double-blind, randomised, placebo-controlled crossover trial will assess the effects of daily consumption for 4 weeks of a novel phytochemical- and fibre-rich granola snack created by TulaCode on menopausal symptoms. The effects of the snack will be compared to a calorie-matched placebo snack: a commercially available oat bar low in fibre and polyphenols. The study will also examine the impact of the intervention snack on mood, stress, sleep quality, cognition, depression and anxiety. Participants will be randomly assigned to either the intervention or the placebo snack for 4 weeks followed by a 4-week washout period before crossing over to the alternate snack for another 4 week period. Snacks will be consumed twice daily, and participants will be instructed to maintain their usual diet and physical activity while avoiding additional probiotic, prebiotic, or polyphenol-rich supplements throughout the study. Participants will attend 4 in-person study visits at King's College London. At baseline, after 4 weeks, after 8 weeks (washout period) and after 12 weeks. Each study visit will take approximately 1 hour. On the day before each study visit, participants will be asked to self-collect their saliva, 24-h urine and stool samples at home, as well as finish a set of online questionnaires, and be fasted for 12 hours prior to their study visit. Self-collection procedure of participants at home one day before study visits: 1. Collect a total of 6 saliva samples throughout the day to measure cortisol levels and fill the saliva collection booklet. 2. Collect a 24 h urine sample, starting in the morning after the first void urine, and finishing the next day collecting the first urine of the day (morning of the study visit day). 3. Collect a small stool sample throughout the day for gut microbiome analysis. 4. Fill the below online questionnaires: 1. Positive and Negative Affect Schedule (PANAS-SF) questionnaire 2. Hospital Anxiety and Depression Scale (HADS) 3. Menopause Rating Scale (MRS) 4. Cognitive Failure Questionnaire (CFQ) 5. Perceived Stress Scale (PSS) 6. World Health Organisation Quality of Life assessment instrument (EF-WHOQOL-100) 5. Weekly questionnaire, 4 questionnaires per visit: 1. International Physical Activity Questionnaire (IPAQ) 2. Pittsburgh Sleep Quality Index (PSQI) 3. Online 24 h dietary recall (Intake 24) 4. 24h picture log of meals (OPIS) 5. Gastrointestinal Symptom Rating Scale (GSRS) 6. Menopause Rating Scale (MRS) 6. Fill the below paper questionnaires: 1. Food-Frequency Questionnaire - EPIC (only for visit 2) 2. Food-Frequency Questionnaire - KCL polyphenol (only for visit 4) On the morning of each study visit day, participants will bring their self-collected saliva, urine, and stool samples. Any Adverse events will be discussed and recorded. Any concomitant medication will be checked by the researchers that may impact on the eligibility criteria and the early completion of the study. Self-collected samples and completed online questionnaires will be checked. Blood pressure, heart rate and anthropometric measurements will be performed, waist-hip circumference will be measured, and fasting blood samples will be collected. On Visit 1 (baseline), either intervention snack or a calorie-matched placebo snack will be provided to participants, with the amount should be enough for the 4-week study period. On Visit 3 (after 8 weeks), the crossover snacks will be provided to participants. At the end of visit 1, 2 and 3, new self-collection kits and a link of online questionnaires will be distributed to participants to be used for next study visit.
Interventions
DIETARY_SUPPLEMENTFunctional Snacks
A type of phytochemical and fibre rich snack that created and produced by TulaCode called Cinnamon Granola Bark (50 g per pouch). The snack contains the following ingredients: Amaranth, coconut flakes, chia seeds, pumpkin seeds, sunflower seeds, pecans, brazil nuts, almonds, dates, banana, cold pressed extra virgin olive oil, 100% cocoa mass, cocoa butter, chicory root fibre, cinnamon, cloves, nutmeg, ginger, ground vanilla pod, natural Bourbon vanilla flavouring, salt
OTHERPlacebo Snacks
A type of calorie-matched commercially available chocolate snack, Mini Cornflake Cluster Bites (50 g per pouch). The snack contains the following ingredients: Milk chocolate (60%) (sugar, cocoa butter, cocoa mass, skimmed milk powder, milk fat, lactose (milk), emulsifier (soya lecithin)), corn flakes (40%) (maize, sugar, salt, barley malt extract, dextrose, niacin, iron, vitamin B6, riboflavin, vitamin B1, folic acid, vitamin B12)
Sponsors
King's College London
Tulā Code Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults aged 40 to 55 * Score 14 or higher on the Menopause Rating Scale * For intervention purposes, eligible participants are also required to have a mobile phone and be able to read and speak English.
Exclusion criteria
* People who consume more than 15g of fibre a day * People who consume more than 2 cups of coffee or tea a day * People who consume more than 4 portions (portion = 80g) of fruits and vegetables a day * People who do not have any intolerances or allergies to the following: * Any kinds of nuts including tree nuts, peanuts, hazelnuts and coconuts * Chia seeds * Pumpkin seeds * Sunflower seeds * Dates * Gluten * Dairy * Oats * Barley * Soya * People who smoke or vape or have smoked or vaped in the last 2 years * People who consume more than 21 drinks a week or have a history of excess alcohol intake * People with comorbid conditions that may limit participation in the study, such as a history of an acute cardiovascular event, including coronary artery disease, previous myocardial infarction (heart attack), stroke, peripheral artery disease, diabetes mellitus, chronic kidney disease, metabolic syndrome, malignancies, cardiac arrhythmia, renal failure, cardiac failure, uncontrolled hypertension, cancer or major psychiatric or cognitive problems * People receiving drug treatment for lipid metabolisms (e.g., statins) * People with a history of long-term use of medicines known to influence glucose metabolism (e.g., corticosteroids) or aspirin * People taking antihypertensive drugs * People who take antibiotics or bacterial agents (Probiotics) within 1 month * People who take vitamin/dietary supplements within 1 month * Pregnant women, women ready for pregnancy, and nursing mothers * cardiac arrhythmia * renal failure * heart failure (NYHA II-IV) * diabetes mellitus * Malignant disease * People who have participated in a biomedical study within the past 3 months * Women who require hormone replacement therapy during the development of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in menopause rating scale (MRS) of perimenopausal women | Baseline & 4 weeks | To assess menopause-related symptoms of perimenopausal women, using the menopause rating scale (MRS). The scale consists in 11 items ranging from 0 (none) to 4 (very severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in subjective (perceived) stress level of perimenopausal women | Baseline & 4 weeks | The subjective stress level of perimenopausal women are assessed using the Perceived Stress Scale (PSS) questionnaire. The scale consists in 10 items rated on a 5-point Likert scale. |
| Changes in affect in perimenopausal women | Baseline & 4 weeks | To assess the affect of perimenopausal women, using the Positive and Negative Affect Schedule (PANAS-SF) questionnaire, consisting of 20 items rated from 1 (very slightly or not at all) to 5 (extremely). |
| Changes in female sex hormone levels of perimenopausal women | Baseline & 4 weeks | To assess the female sex hormone levels of perimenopausal women, measured several esterone levels in blood samples using the randox clinical biochemistry analyser. |
| Changes in cognitive function of perimenopausal women | Baseline & 4 weeks | To assess cognitive function of perimenopausal womenm using Cognitive Failures questionnaire (CFQ). The questionnaire consists of 25 questions rated on a 5-point Likert scale from 0 ("Never") to 4 ("Very often"). |
| Changes in mental health and wellbeing metabolites level of perimenopausal women | Baseline & 4 weeks | To assess the metabolites related to mental health and wellbeing of perimenopausal women, measured a pack of metabolites/compounds including gut-brain axis metabolites, inflammatory markers, short-chain fatty acid, in plasma samples using Randox clinical biochemistry analyser and LC-MS. |
| Habitual diet of perimenopausal women | Baseline only | Habitual diet is assessed via the food frequency questionnaire (FFQ), items ranging from "never" to "multiple times a day"-they consumed specific food and beverage items from a predefined list |
| Gut microbiome of perimenopausal women | Baseline & 4 weeks | To investigate the role of the gut microbiome on the perimenopause symptoms. Gut microbiome diversity and composition will be analysed using 16s RNA sequencing technique as a pack. |
| Changes in hormonal stress levels in perimenopausal women | Baseline & 4 weeks | Stress measured as the cortisol level changes in saliva samples by LC-MS, including the cortisol levels at 0 min, 15 min, 30 min and 60 min after wakening and 12 pm and 8 pm on the day. |
| Changes in mood in perimenopausal women | Baseline & 4 weeks | To assess the overall changes in mood, using the Hospital Anxiety and Depression Scale (HADS), consist of 14 items rated on a 0-21 scale, with a higher score indicates a severe symptom. |
| Changes in sleep quality in perimenopausal women | Weekly from baseline to 4 weeks | Sleep quality changes measured using Pittsburgh Sleep Quality Index (PSQI) questionnaire, consist of 19 items rated on a 0-3 scale with higher scores indicating poorer sleep quality. |
| Changes in physical activity level in perimenopausal women | Weekly from baseline to 4 weeks | Changes in physical activity measured using the International Physical Activity questionnaire (IPAQ), producing a total activity score expressed in metabolic equivalent minutes per week (MET-min/week). |
| Changes in quality of life in perimenopausal women | Baseline & 4 weeks | Changes in quality of life measured using the World Health Organisation Quality of Life Assessment Instrument (EF-WHOQOL-100), a 100 item questionnaire with responses rated on a 1-5 Likert scale |
| Changes in gastrointestinal symptoms of perimenopausal women | Weekly from baseline to 4 weeks | Changes in the gastrointestinal function measured using Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, consisting of 15 items rated from 1 (no discomfort) to 7 (very severe discomfort). |
| Changes in weight of perimenopausal women | Baseline & 4 weeks | Weight will be measured in kilograms using a body composition analyser (Tanita BC-418 MA) |
| Height of perimenopausal women | Baseline | Height in centimeters will be measured using a stadiometer |
| Changes in BMI of perimenopausal women | Baseline & 4 weeks | Changes in BMI will be measured by weighing participants using the body composition analyser (Tanita BC-418 MA) and calculating BMI from participant height and weight |
| Changes in hip-waist circumference of perimenopausal women | Baseline & 4 weeks | Hip and waist circumference will be measured in centimeters using a measuring tape |
| Changes in blood pressure of perimenopausal women | Baseline & 4 weeks | Blood pressure will be measured using an electric sphygmomanometer blood pressure monitor in millimeters of mercury (mmHg). |
| Heart rate of perimenopausal women | Baseline & 4 weeks | Heart rate will be measured in beats per minute using an electric sphygmomanometer blood pressure monitor |
| Dietary polyphenol intake of perimenopausal women | Baseline | Polyphenol intake measured via the Food-Frequency Questionnaire - Polyphenol. Food items are rated from "Never" to "More than 6 times per day". |
| Weekly diet of perimenopausal women | Weekly from baseline to week 4 | Weekly diet using Intake24, an online 24-hour dietary recall system that records all foods and drinks consumed during the previous day. It uses portion-size images and structured prompts to improve accuracy and reduce under-reporting. |
Countries
United Kingdom
Contacts
CONTACTAna Rodriguez-Mateos, PhD
CONTACTZicheng Zhang, PhD
PRINCIPAL_INVESTIGATORAna Rodriguez-Mateos, PhD
King's College London
Outcome results
None listed