Circadian Health Regulation and Optimization for Rejuvenation Outcomes

Not Applicable

Recruiting

• Conditions: Aging, Healthy; Blood Sugar; High; Blood Sugar (Glucose) Control; Time Restricted Eating; Circadian Dysregulation

• Registration Number: NCT07203196
• Lead Sponsor: Salk Institute for Biological Studies

Brief Summary

In this single arm intervention trial, the investigators will assess the impact of a personalized lifestyle plan, centered on supporting biological rhythms, on blood sugar levels, physical, cognitive and immune function in older adults with a habitual eating window of 12 hours or more, and elevated blood glucose levels.

All participants will be provided with a personalized circadian rhythm optimization plan (CRO) centered on improving (1) diet, (2) exercise (3) sleep habits based on their body's natural rhythms. The study includes a 2-week screening/baseline assessments, with follow-up health assessments at 2-months.

Detailed Description

The purpose of this study is to assess if modifying lifestyle behaviors such as improving nutrition quality while consolidating caloric intake to a consistent 8-10 hour window, incorporating regular exercise and ensuring a consistent sleep window will help improve glucose (sugar) regulation, physical, cognitive and immune function and improve other markers of metabolic, cardiovascular health and aging (i.e. lipid levels, inflammation markers, etc.).

Circadian clocks ("circa" means approximately and "dia" means day) are daily rhythms in physiology and behavior (activity, sleep, eating pattern) that help the body anticipate and adapt to predictable events in the environment. These rhythms are generated and maintained by biological clocks that are present in the brain and almost every organ. Remarkably, even in the absence of any timing information from a device, the human body can keep track of time and thereby help us eat and sleep at optimum times. However, our lifestyle and work schedules can lead us to eat, exercise, and sleep at times that the clocks in our body are not prepared for. When these abnormal daily patterns continue for several weeks or years, it can affect our health in many ways including increased body weight, poor sleep, and elevated risk for various chronic diseases.

A growing body of preclinical research has shown that synchronizing behaviors, such as food intake, exercise, and light exposure, with the body's biological clock improves skeletal muscle function, cognitive performance, and inflammatory markers. Clinical studies have further validated these findings, showing that circadian-based interventions, such as time-restricted eating (TRE), which restricts all caloric intake to a personalized consistent daily eating window, daytime light exposure and exercise have been shown to improve mood, sleep quality and cardiometabolic health. Despite these promising individual findings, no study has comprehensively examined the combined effects of TRE, structured exercise and optimized sleep schedule as an integrated strategy to restore circadian alignment and reverse key physiological markers of aging in older adults.

In this study, the investigators are interested in evaluating the effects of modifying eating, activity and sleeping patterns on age related health outcomes in older adults with elevated blood sugar levels. All participants will be provided with a personalized circadian rhythm optimization (CRO) program centered on (1) consuming a Mediterranean diet within a personalized 8-10-hour daytime window, (2) increasing daytime light exposure and reducing bright light at night, (3) incorporating 150 minutes of moderate-intensity aerobic exercise each week (4) holding a consistent 7-9 hour sleep schedule (5) taking supplements based on individual needs.

The study is 90-days including a 2-week screening/baseline assessment followed by a 2-week period to developed their personalized plan based off their baseline assessments and finally a 8-week guided intervention period. Health assessments will be taken at screening/baseline, and at 90 days. Assessments will include cognitive function (cognitive assessment battery), physical function (VO2 Max, isometric strength, short physical performance battery), dietary recall (ASA24), blood tests (biomarkers of cardiometabolic health and immune parameters), glycemic regulation (Continuous Glucose Monitors), body composition ( bioelectrical impedance scan), dietary intake (logged on the myCircadianClock smartphone app), sleep and quality of life questionnaires, and activity, sleep, and wrist temperature (actigraphy watch) and subclavian and ankle surface temperature (non-invasive temperature sensor).

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-12
• Study First Submitted QC: 2025-09-29
• Last Update Submitted: 2025-09-29
• Study First Posted: 2025-10-02
• Last Update Posted: 2025-10-02
• Study Start: 2025-10-22
• Primary Completion: 2026-04-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Age: 50-80 years
2. Fasting glucose ≥ 100 mg/dL or HbA1c > 5.6%
3. Own a smartphone (Apple iOS or Android OS)
4. Proficient in reading and speaking in English
5. An eating window ≥12 hour/day
6. Willing to travel to sports facilities for exercise training sessions
7. Participants on cardiovascular medications (HMG CoA reductase inhibitors (statins), metformin, SLGT2 inhibitors, GLP1 receptor agonists other lipid-modifying drugs (including over-the counter drugs such as red yeast rice and fish oil), anti-hypertensive, drugs), are allowed if on a stable dose for 6-months, but dose adjustments are not allowed during the study

Exclusion Criteria

1. Insufficient dietary logging on the mCC app during screening, defined as less than 7 of 14 days of baseline of dietary logging with a minimum of 2 items a day, at least 5 hours apart
2. Type 1 Diabetes or Insulin-dependent Type 2 Diabetes
3. HbA1C > 9.0%
4. Use of sulfonylurea or insulin within the last 3 months (due to unknown safety with TRE)
5. Change in medications that could impact study outcomes within the past 6 months
6. Change in weight of >4kg in the past 3 months
7. Systolic BP greater than 160 mmHg and/or diastolic BP greater than 110 mmHg at rest
8. Fasting LDL cholesterol greater than 250 mg/dL
9. Fasting triglycerides greater than 500g/dL
10. Variable work hours, such as working night shifts
11. Caregiver for a dependent requiring frequent nocturnal care/sleep interruptions
12. Active tobacco use, illicit drug use, or history of treatment for alcohol abuse in the past 5 years.
13. Travel involving a time zone change of more than 3 hours twice or more during the study period
14. Active treatment for inflammatory and/or rheumatologic disease
15. History of a major adverse cardiovascular event within the past year (acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack)
16. Uncontrolled arrhythmia (i.e. rate-controlled atrial fibrillation/atrial flutter are acceptable)
17. Previously diagnosed with sever aortic stenosis
18. Previously diagnosed with sever COPD (FEV1/FVC ratio <.7 & FEV1 (%predicted) <49
19. Orthopedic impairments severely compromising exercise performance
20. BMI <18.5 kg/m2
21. History of thyroid disease requiring dose titration of thyroid replacement medication(s) within the past 6 months (i.e. hypothyroidism on a stable dose of thyroid replacement therapy is not an exclusion).
22. History of adrenal disease in the past 5 years
23. History of malignancy undergoing active treatment, except non-melanoma skin cancer, in the past 5 years
24. History of an eating disorder in the past 5 years
25. History of cirrhosis in the past 5 years
26. History of stage 4 or 5 chronic kidney disease or dialysis in the past 5 years
27. History of HIV/AIDs
28. Currently enrolled in weight-loss or weight-management program
29. Regularly engages in 100 minutes or more of structured exercise
30. VO2 max threshold is above average for that individuals age group [78]
31. Uncontrolled psychiatric disorder including prior hospitalization

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
HbA1c (%)	Baseline and 90 days	HbA1c levels (%) as assessed by fasting blood draw

Secondary Outcome Measures

Name	Time	Method
IL-7 (pg/mL)	Baseline and 90 days	IL-7 (pg/mL) assessed through fasting blood draw
IL-8	Baseline and 90 days	IL-8 (pg/mL) assessed through fasting blood draw
IL-9 (pg/mL)	Baseline and 90 days	IL-9 (pg/mL) assessed through fasting blood draw
IL-10 (pg/mL)	Baseline and 90 days	IL-10 (pg/mL) assessed through fasting blood draw
IL-12p70 (pg/mL)	Baseline and 90 days	IL-12p70 (pg/mL) assessed through fasting blood draw
IL-13 (pg/mL)	Baseline and 90 days	IL-13 (pg/mL) assessed through fasting blood draw
IL-15 (pg/mL)	Baseline and 90 days	IL-15 (pg/mL) assessed through fasting blood draw
IL-16 (pg/mL)	Baseline and 90 days	IL-16 (pg/mL) assessed through fasting blood draw
IL-17A (pg/mL)	Baseline and 90 days	IL-17A (pg/mL) assessed through fasting blood draw
IL-17F (pg/mL)	Baseline and 90 days	IL-17F (pg/mL) assessed through fasting blood draw
IL-18 (pg/mL)	Baseline and 90-days	IL-18 (pg/mL) assessed through fasting blood draw
IL-20 (pg/mL)	Baseline and 90 days	IL-20 (pg/mL) assessed through fasting blood draw
IL-21 (pg/mL)	Baseline and 90 days	IL-21 (pg/mL) assessed through fasting blood draw
IL-22 (pg/mL)	Baseline and 90 days	IL-22 (pg/mL) assessed through fasting blood draw
IL-23 (pg/mL)	Baseline and 90 days	IL-23 (pg/mL) assessed through fasting blood draw
IL-27 (pg/mL)	Baseline and 90 days	IL-27 (pg/mL) assessed through fasting blood draw
IL-28 (pg/mL)	Baseline and 90 days	IL-28 (pg/mL) assessed through fasting blood draw
IL-33 (pg/mL)	Baseline and 90 days	IL-33 (pg/mL) assessed through fasting blood draw
MCP-1 (pg/mL)	Baseline and 90 days	MCP-1 (pg/mL) assessed through fasting blood draw
MCP-2	Baseline and 90 days	MCP-2 (pg/mL) assessed through fasting blood draw
MCP-3 (pg/mL)	Baseline and 90 days	MCP-3 (pg/mL) assessed through fasting blood draw
MCP-4 (pg/mL)	Baseline and 90 days	MCP-4 (pg/mL) assessed through fasting blood draw
TGFα (pg/mL)	Baseline and 90 days	TGFα (pg/mL) assessed through fasting blood draw
TNFβ (pg/mL)	Baseline and 90 days	TNFβ (pg/mL) assessed through fasting blood draw
EGF (pg/mL)	Baseline and 90 days	EGF (pg/mL) assessed through fasting blood draw
Grip Strength	Baseline and 90 days	Maximal grip force (Kg)
Isometric Knee Strength	Baseline and 90 days	Maximal force output for knee flexion and extension (Kg)
VO2 Max	Baseline and 90 days	Maximal oxygen consumption (mL/kg/min).
Time to 80% Maximal Aerobic Capacity	Baseline and 90 days	Time to 80% of maximal aerobic capacity (mins).
Flanker Inhibitory and Control and Attention Test (Fully-Corrected T-score)	Baseline and 90 days	Flanker Inhibitory and Control and Attention Test (Fully-Corrected T-score) assessed through NIH cognitive assessment battery. The score compares an individual's cognitive performance to a nationally representative norming sample correcting for age, sex, race/ethnicity, and educational attainment.
Dimensional Change Card Sort (Fully-Corrected T-score)	Baseline and 90 days	Dimensional Change Card Sort (Fully-Corrected T-score) assessed through NIH cognitive assessment battery. The score compares an individual's cognitive performance to a nationally representative norming sample correcting for age, sex, race/ethnicity, and educational attainment.
Pattern Comparison Processing Speed Test (Fully-Corrected T-score)	Baseline and 90 days	Pattern Comparison Processing Speed Test (Fully-Corrected T-score) assessed through NIH cognitive assessment battery. The score compares an individual's cognitive performance to a nationally representative norming sample correcting for age, sex, race/ethnicity, and educational attainment.
Glucagon (pg/mL)	Baseline and 90 days	Glucagon (pg/mL) assessed through fasting blood draw
Picture Sequence Memory test (Fully-Corrected T-score)	Baseline and 90 days	Picture Sequence Memory test (Fully-Corrected T-score) assessed through NIH cognitive assessment battery. The score compares an individual's cognitive performance to a nationally representative norming sample correcting for age, sex, race/ethnicity, and educational attainment.
Trail Making Test	Baseline and 90 days	Trail making test part A and B will be assessed by the time to completion (seconds) for each assessment.
Leptin (ng/mL)	Baseline and 90 days	Leptin (ng/mL) assessed through fasting blood draw
IL-1α (pg/mL)	Baseline and 90 days	IL-1α (pg/mL) assessed through fasting blood draw
IL-1β (pg/mL)	Baseline and 90 days	IL-1β (pg/mL)assessed through fasting blood draw
IL-6 (pg/mL)	Baseline and 90 days	IL-6 (pg/mL) assessed through fasting blood draw
IL-2 (pg/mL)	Baseline and 90 days	IL-2 (pg/mL) assessed through fasting blood draw
IL-3 (pg/mL)	Baseline and 90 days	IL-3 (pg/mL) assessed through fasting blood draw
IL-4 (pg/mL)	Baseline and 90 days	IL-4 (pg/mL) assessed through fasting blood draw
IL-5 (pg/mL)	Baseline and 90 days	IL-5 (pg/mL) assessed through fasting blood draw
TNF-α (pg/mL)	Baseline and 90 days	TNF-α (pg/mL) assessed through fasting blood draw
Ghrelin (pg/mL)	Baseline and 90-days	Ghrelin (pg/mL) assessed through fasting blood draw
IGF-1 (ng/mL)	Baseline and 90 days	IGF-1 (ng/mL) assessed through fasting blood draw
IGF-2 (ng/mL)	Baseline and 90 days	IGF-2 (ng/mL) assessed through fasting blood draw
IL-1RA (pg/mL)	Baseline and 90 days	IL-1RA (pg/mL) assessed through fasting blood draw
TRAIL (pg/mL)	Baseline and 90 days	TRAIL (pg/mL) assessed through fasting blood draw
VEGF-A (pg/mL)	Baseline and 90 days	VEGF-A (pg/mL) assessed through fasting blood draw
IGFBP-1 (ug/mL)	Baseline and 90 days	IGFBP-1 (ug/mL) assessed through fasting blood draw
GIP (pg/mL)	Baseline and 90-days	GIP(pg/mL) assessed through fasting blood draw
GLP-1 (pmol/L)	Baseline and 90 days	GLP-1 (pmol/L) assessed through fasting blood draw.
Total Recall (T-score)	Baseline and 90-days	Total Recall (T-score) as assessed through Hopkins Verbal Learning Test - Revised. T-score is adjusted for participant's age.
Delayed Recall (T-score)	Baseline and 90-days	Delayed Recall (T-score) as assessed through Hopkins Verbal Learning Test. T-score is adjusted for participant's age.
Retention Percentage (T-score)	Baseline and 90-days	Retention Percentage (T-score) as assessed through Hopkins Verbal Learning Test - Revised. T-score is adjusted for participant's age.
Recognition Discrimination Index (T-score)	Baseline and 90-days	Recognition discrimination index as assessed through Hopkins Verbal Learning Test-Revised. T-score is adjusted for participant's age.
Cognition Fluid Composite (Fully-Corrected T-score)	Baseline and 90-days	Cognition Fluid Composite (Fully-Corrected T-score) as assessed through a composite score of several tests, namely the Flanker inhibitory control and attention test, the dimensional change card sort test, the picture sequence memory test, the list sorting working memory test, and the pattern comparison processing speed test. The score compares an individual's cognitive performance to a nationally representative norming sample correcting for age, sex, race/ethnicity, and educational attainment.

Trial Locations

Locations (1)

University of California San Diego; 🇺🇸 La Jolla, California, United States