The Impact of Overnight Active Temperature Regulation on Gut Microbiome, Inflammation, and Circadian Rhythm.

Inclusion criteria

• All Cohorts
• 45 years of age or older
• Self-reported poor sleep quality: PSQI score greater than 5
• Within 1.5 hours driving of the Greater Boston area
• Have never used an Eight Sleep Pod (or similar device) ever
• Post-enrollment hsCRP ≤ 10 µg/mL at Preparation Period blood panel. If Preparation Period hsCRP \> 10 µg/mL: triggers clinical review on a case by case basis; hard

Exclusion criteria

• applies only at \> 30 µg/mL Weight ≥ 88 lbs
• No MRI scheduled during the study period or within 1 week after study conclusion
• No acute illness, injury, or dental procedure/cleaning within 3 months prior to study start
• Non-smoker or previous infrequent (\<1 weekly) smoker who has ceased at least 3 months prior to study start
• Predictable bowel movements: at least 3 weekly and no more than 3 daily bowel movements
• Able to drive or be transported to a local lab facility at least three total times for blood panels
• Willing to complete 3 blood panels (3-4 tubes of blood collected at each draw): no strong aversion to needles
• Able to swallow a pill/capsule (approximately the size of the standard vitamin capsule) for internal core temperature monitoring
• Stable diet for a minimum of 3 months prior to enrollment, with no planned major dietary changes during the study period
• Stable medication regimen: no medication type or dose changes within 3 months prior to study start, and no plans to change medications during the study. This includes long-term -medication like antidepressants, statins, hormones, antihypertensives, or levothyroxine.
• Stable exercise routine for a minimum of 3 months prior to study start, with no planned changes to this routine
• Stable dietary supplement routine for a minimum of 3 months prior to the study start: includes probiotics, synbiotics, supplemental SCFA's
• Willing to receive, set-up, and use all required equipment: the Eight Sleep Pod Cover and Hub, biometric smart ring, urine-based hormone measurement kit, ambulatory blood pressure monitor, core temperature capsule, HST device, and stool collection kits for the required amount of time
• Comfortable using research accounts owned by Eight Sleep for some study devices
• Willing and able to have stool samples picked up by the research team three and up to five times during the study
• Willing to have the research team in the home for study set-up (up to 3 hours)
• Have a valid, government issued ID Cohort A specific Inclusion: Postmenopausal women
• Assigned female at birth
• Postmenopausal: self-reported absence of menstrual period for 12 or more consecutive months prior to study start
• No change to hormone replacement therapy (HRT) use within 3 months prior to study start or plans to change HRT status during study period
• No changes to hormonal birth control use within 3 months prior to study start or plans to change birth control use during study period Cohort B specific Inclusion: Age-Matched Men -Assigned Male at birth Exclusion Criteria: All Cohorts
• Currently taking any of the following medications/supplements or have changed use status (using to not using or vice versa) within 3 months before study start.
• Antibiotics (any kind), including one-time or short-term antibiotic use
• Corticosteroids (oral or injection only, topical preparations included):
• Prednisolone
• Dexamethasone
• Hydrocortisone
• Methylprednisolone (Medrol)
• Betamethasone
• Anti-TNF-α medications (biologics for arthritis, Crohn's disease, psoriasis, or other immune/inflammatory conditions):
• Adalimumab (Humira)
• Etanercept (Enbrel)
• Infliximab (Remicade)
• Certolizumab (Cimzia)
• Golimumab (Simponi)
• Changed use status (using to not using or vice versa) within 3 months before study start or plans to stop/start the medications during the study. --Statins (cholesterol-lowering medications):
• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)
• Lovastatin (Mevacor)
• Fluvastatin (Lescol)
• Antihypertensive drugs (blood pressure medications):
• Angiotensoconverting enzyme (ACE) inhibitors: Lisinopril, Ramipril, Perindopril, Enalapril
• Angiotensin II receptor blockers (ARBs): Losartan, Valsartan, Candesartan
• Calcium channel blockers: Amlodipine (Norvasc), Diltiazem, Verapamil
• Beta-blockers: Metoprolol, Atenolol, Bisoprolol, Propranolol
• Diuretics: Hydrochlorothiazide, Furosemide (Lasix), Indapamide
• Changed use status (using to not using or vice versa) within 3 months before study start or plans to start/stop during the study.
• Hormonal birth control (any form): ---Combined oral contraceptives (estrogen + progestin) or progestin-only capsule
• Hormonal IUD (e.g. Mirena, Kyleena)
• Contraceptive implant (e.g. Nexplanon)
• Contraceptive injection (e.g. Depo-Provera)
• Contraceptive patch (e.g. Xulane, Evra)
• Vaginal ring (e.g. NuvaRing)
• Hormone replacement therapy (exceptions: systemic - local vaginal estrogen preparations are not excluded):
• Estrogen-based: oral tablets, patches, gel, cream, or vaginal ring
• Combined estrogen + progestogen: oral tablets or patches
• Progesterone-based: oral tablets or intrauterine device
• Testosterone: cream or gel
• Bioidentical: oral tablets, patches, gel, cream, pellets, or injections
• Currently taking any of the following medications/supplements or have changed use status (using to not using or vice versa) within 3 months before study start or plans to start/stop during the study. --Anabolic-androgenic steroids or performance-enhancing drugs (prescribed or non-prescribed):
• Testosterone-based: testosterone enanthate, cypionate, propionate, Sustanon
• Synthetic anabolic steroids: nandrolone, stanozolol (Winstrol), oxandrolone (Anavar), methandrostenolone (Dianabol), trenbolone
• GLP-1 receptor agonists or other glucose-lowering medications:
• GLP-1s: Semaglutide (Ozempic, Wegovy), Liraglutide (Victoza, Saxenda), Dulaglutide (Trulicity), Tirzepatide (Mounjaro, Zepbound)
• Other: Metformin (Glucophage), Insulin (all types), Sitagliptin (Januvia), Empagliflozin (Jardiance), Dapagliflozin (Farxiga), Glipizide, Glyburide
• Currently taking any of the following medications/supplements or have changed use status (using to not using or vice versa) within 3 months before study start or plans to start/stop taking these drugs during the study period. --Sleep medications: Prescription: Zolpidem (Ambien), Zopiclone (Imovane), Eszopiclone (Lunesta), Temazepam, Nitrazepam, Trazodone (when prescribed for sleep), Suvorexant (Belsomra) Over-the-counter: Diphenhydramine (Benadryl, ZzzQuil, Unisom), Doxylamine (Unisom SleepTabs, Nytol), --Benzodiazepines (use status change within 12 months before study start): Diazepam (Valium), Lorazepam (Ativan), Clonazepam (Klonopin), Temazepam, Nitrazepam
• Antidepressant medications (change within 3 months of study start or plans to start/stop taking during the study period)
• Stimulants affecting blood pressure:
• Methylphenidate (Ritalin, Concerta)
• Amphetamine/Dextroamphetamine (Adderall)
• Lisdexamfetamine (Vyvanse)
• Modafinil (Provigil)
• Pseudoephedrine (Sudafed, including other cold/decongestant medications)
• Antipsychotics: Quetiapine (Seroquel), Olanzapine (Zyprexa), Risperidone
• Mood stabilizers: Lithium, Valproate (Depakote)
• Changed use status (using to not using or vice versa) within 3 months before study start or during the study. --CBT-I or pharmacological treatment for insomnia disorder
• Changed use status (started or stopped using) within 3 months before study start.
• Probiotics, prebiotics, or synbiotics
• Butyrate (Sodium butyrate, Calcium/magnesium butyrate, Tributyrin), Acetate, Propionate
• Multivitamins containing any of the following minerals:
• Iron, Selenium, Calcium, Zinc, Phosphorus, Magnesium Note: Stable long-term multivitamin use (unchanged for ≥3 months) is not excluded Folic Acid, Vitamin C, Vitamin A, Vitamin D, or Vitamin E supplements
• Antioxidant supplements
• Omega-3 / fish oil supplements
• Melatonin (current use excluded if unwilling to cease use during study participation)
• Current, ongoing, or history of diagnosis or changed diagnosis status (new diagnosis, revised or reversed diagnosis) within the specified timeframe.
• Metabolic Conditions
• Diabetes mellitus: Type 1
• Type 2 diabetes (within the past 3 years)
• Diagnosed prediabetes (confirmed via Preparation Period hbA1c levels. A result between 5.7-6.4% warrants exclusion from the study)
• Chronic hepatitis B/C
• Liver cirrhosis
• Alcoholic liver disease
• Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) (within the past 3 years)
• Hepatitis A (within the past 3 years)
• Hypothyroidism or hyperthyroidism (including Hashimoto's thyroiditis)
• Cardiovascular Conditions
• Hypertension
• Cardiovascular disease, including:
• Coronary artery disease (CAD) or ischemic heart disease
• History of myocardial infarction (heart attack)
• Heart failure (any grade)
• Atherosclerosis
• History of stroke or transient ischemic attack (TIA)
• Peripheral arterial disease (PAD)
• Atrial fibrillation or other major cardiac arrhythmias
• Vasovagal syncope: common fainting episode caused by a sudden drop in blood pressure and heart rate
• Severe anemia or significant white blood cell or platelet abnormalities
• Surgery, severe skin disease, or fistula on the upper arm (interfering with BP cuff readings; within 3 months prior to the study start)
• Autoimmune Conditions
• Rheumatoid arthritis
• Ankylosing spondylitis
• Lupus erythematosus
• Multiple sclerosis (MS)
• Any other diagnosed autoimmune condition or current use of immunosuppressive medications
• Gastrointestinal Conditions
• Inflammatory bowel disease (IBD), Crohn's disease or ulcerative colitis
• Irritable bowel syndrome (IBS)
• Celiac disease
• Gastroparesis or diverticular disease
• History of colostomy, colon cancer, or other colon-related surgeries
• Recent gastrointestinal surgery (within 6 months prior to enrollment)
• Chronic Diseases
• Renal disease (chronic kidney disease, any stage)
• Hepatic disease (beyond those listed under metabolic conditions above)
• Respiratory or chronic lung disease
• Neurological and Psychological Conditions
• Alzheimer's disease
• Parkinson's disease
• Schizophrenia
• Sleep-Related Conditions
• Obstructive sleep apnea (OSA)
• Central sleep apnea
• Complex sleep apnea syndrome
• Narcolepsy or hypersomnia disorders
• Restless legs syndrome (RLS) / Willis-Ekbom disease
• Periodic limb movement disorder (PLMD)
• Circadian rhythm sleep-wake disorders: shift work disorder (SWD), irregular sleep-wake rhythm disorder (ISWRD), or non-24-hour sleep-wake disorder (N24SWD) Note: Participants with delayed sleep-wake phase disorder (DSWPD) or advanced sleep-wake phase disorder (ASWPD) with chronically stable sleep timing may be included.
• Participants will be excluded if they participate in any of the following behaviors or conditions within the indicated timeframe.
• Substance Use
• Current addiction to opiates
• Excessive alcohol consumption (more than 14 standard drinks per average 1 week)
• Habitual caffeine consumption exceeding 400 mg per day (approximately 4 standard cups of coffee or equivalent)
• Recreational frequent drug use within timeframes noted prior to study start:
• Cannabis / marijuana (including edibles and oils): daily or near-daily use (defined as ≥5 days per week) within 3 months prior to study start
• Cocaine: any use within 3 months prior to study start
• MDMA / ecstasy: any use within 3 months prior to study start
• Hallucinogens (LSD, psilocybin): any use within 4 weeks prior to study start
• Ketamine or other illicit substances: any use within 3 months prior to study start
• Diet and Weight
• Planning significant changes to diet or lifestyle in the 3 months prior to study start, or had significant changes to diet or lifestyle in the 3 months prior to study start
• Starting or stopping a specialized diet (ketogenic, vegan, carnivore, elimination, intermittent fasting)
• Significant increase or decrease in exercise load or training plan (change of ≥60 minutes per week in total exercise volume, starting or stopping a structured exercise program, or injury/illness-related activity restriction) within 3 months prior to study start
• Currently enrolled in an active weight-loss program, bariatric program, or medically supervised diet, or planning to start one during the study
• Weight loss or gain within the past 1 month of 5% of body weight or greater,, or weight loss or gain within the past 6 months of 10% body weight or greater
• Health Status at Enrollment ---Acute illness or active infection at the time of recruitment or study start: includes colds, prolonged cough, fevers, etc.
• Active cancer diagnosis or receipt of chemotherapy or radiotherapy within 12 months prior to study start, or planned chemotherapy treatment during the study duration
• Hospitalization of greater than 24 hours for acute illness, major surgery, sepsis, or cardiac, pulmonary or neurological events within 6 months prior to study start
• Study Equipment Compatibility
• Unable or unwilling to swallow a standard-sized capsule (required for internal core temperature monitoring capsule)
• Currently using a pacemaker or other electromagnetic medical implant (contraindicated with core temperature capsule)
• MRI scheduled during the study period or within 1 week after study conclusion
• Have or may have a CT scan planned during the study period
• Allergic to nickel or aluminum
• Sample and Data Collection ---Unable or unwilling to ----Collect and provide at least 3, and up to 5, stool samples ----Store self-collected stool samples in a home freezer until shipment/pick-up (up to 1 week after collection) ----Complete 3 blood panels (3-4 tubes of blood each), including strong aversion to needles ----Complete required digital surveys and any requested data sharing
• Communicate with the research team within a timely manner throughout the duration of the study
• Have stool samples picked up from home
• Have research staff within home for study set-up for up to 3 hours
• Complete all data collection requirements in a timely manner
• Lifestyle and Compliance
• Travel planned during the study period
• Unstable WiFi connection at any point during the study period (to the best ability this can be predicted)
• Unwilling or unable to provide informed consent with sufficient mental wellness to understand the study
• Lived outside of the United States within 6 months prior to study start Cohort A Exclusion Criteria: Postmenopausal women
• Hysterectomy
• Oophorectomy (single or double)
• Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovarian syndrome (PCOS)
• Diagnosed testosterone dysregulation (hyperandrogenism or androgen insufficiency) not attributable to PMOS
• Premature ovarian insufficiency (POI) or premature ovarian failure (POF)
• Endometriosis
• Change to hormone replacement therapy (HRT) use within 3 months prior to study start
• Changes to hormonal birth control use within 3 months prior to study start Cohort B Exclusion Criteria: Age-Matched Men -Diagnosed testosterone dysregulation (hyperandrogenism and/or androgen insufficiency)