Sleep Restriction for Metabolic Health

(SAM Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Andrew McHill, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Oregon Health and Science University

Must not be taking: Antidepressants, Neuroleptics, Tranquilizers

Disqualifiers: Psychiatric disorders, Hypertension, Diabetes, Respiratory diseases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this study is to uncover sleep and circadian mechanisms contributing to adverse metabolic health. The protocol is a 21 day (7 outpatient days, 14 inpatient days) mechanistic randomized-crossover study designed to identify the impact of chronic sleep restriction and circadian timing, independently and in combination on energy metabolism and identify the independent and combined effects on glucose tolerance.

Will I have to stop taking my current medications?

Yes, participants must stop taking any prescribed or over-the-counter medications, except for birth control, to be eligible for this study.

What data supports the effectiveness of the treatment Chronic Sleep Restriction, Sleep Deprivation, Partial Sleep Restriction, Chronic Sleep Curtailment for metabolic health?

Research shows that not getting enough sleep can lead to problems like obesity and diabetes because it affects hormones that control hunger and how the body uses energy. Improving sleep could help manage these metabolic issues. ^{1 2 3 4 5}

Is sleep restriction generally safe for humans?

Research suggests that chronic sleep restriction can lead to negative effects on metabolic health, such as increased risk of obesity and diabetes, and can disrupt appetite regulation. It is important to ensure adequate sleep to maintain metabolic health and reduce these risks. ^{1 2 6 7 8}

How does the treatment of chronic sleep restriction differ from other treatments for metabolic health?

Chronic sleep restriction is unique because it focuses on the impact of reduced sleep duration on metabolic health, unlike other treatments that might target diet or exercise. It highlights how insufficient sleep can lead to changes in metabolism, such as reduced insulin sensitivity and altered appetite regulation, which are not typically addressed by standard metabolic health treatments. ^{1 3 6 9 10}

Research Team

Andrew McHill, PhD

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for drug-free adults aged 18-40 with no chronic diseases, a BMI between 18.5 and 25 kg/m2, waist circumference <94/80cm, non-smokers or minimal smoking history. Excludes those with immune, cardiovascular, respiratory disorders; metabolic syndrome; diabetes; sleep disorders; psychiatric conditions; current medication (except birth control); recent shift work or travel across time zones.

Inclusion Criteria

I am not currently taking any medications.

I am between 18 and 40 years old.

My cancer is currently in remission.

Exclusion Criteria

I have a lung or breathing condition.

I have high blood pressure and am taking beta blockers.

You have any severe sleep problems or unusual sleep patterns.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Ambulatory Monitoring

Participants maintain a consistent 7-day at home 8h sleep schedule at habitual times before laboratory visits, verified by actigraphy, sleep logs, and call-ins.

7 days

Daily check-ins (virtual)

Outpatient Diet

Participants consume an isocaloric diet for 3 days prior to each protocol, designed to meet individual daily energy requirements.

3 days

Daily check-ins (virtual)

Inpatient Protocols

Participants undergo a 14-day inpatient protocol with sleep/wake schedule manipulation and ad libitum food access, including sleep restriction and control conditions.

14 days

Continuous monitoring (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Chronic Sleep Restriction (Behavioral Intervention)

Trial Overview The study investigates how lack of sleep and circadian rhythm affect metabolism and glucose tolerance over a period of three weeks. Participants will undergo periods of sleep restriction in a controlled environment to determine the impact on their energy metabolism.

Participant Groups

Group I: Sleep Restriction First Experimental Treatment 1 Intervention

Equivalent to obtaining 5.5.h of sleep per 24h; n=10. Participants live on a 20h-day and will experience 15.33h wake episodes followed by sleep episodes of 4.67h long. Ad libitum food is provided during this time and participants will be fed \~130-150% of their daily caloric needs across three meals a day.

Group II: Controlled Condition First Active Control 1 Intervention

Equivalent to obtaining 8h sleep per 24h; n=10. Participants live on a 20h-day and will experience 13.33h wake episodes followed by 6.67h sleep opportunities. Ad libitum food is provided during this time and participants will be fed \~130-150% of their daily caloric needs across three meals a day.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

Findings from Research

Chronic sleep restriction, defined as sleeping less than 6 hours a night, is linked to increased risks of obesity and metabolic health issues, highlighting its significance for endocrinologists.

Sleep loss triggers metabolic adaptations that can lead to increased food intake and energy conservation, potentially undermining weight loss efforts through diet and exercise in overweight individuals, suggesting the importance of adequate sleep in weight management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on energy homeostasis and insufficient sleep. Penev, PD.[2021]

In a study of overweight or obese adults, those who underwent caloric restriction (CR) alone lost a greater proportion of fat mass compared to those who combined caloric restriction with moderate sleep restriction (CR + SR), despite both groups losing similar amounts of total weight.

Moderate sleep restriction (about 1 hour less sleep on five nights) negatively impacted body composition, leading to less fat loss during a hypocaloric diet, suggesting that sleep quality may play a crucial role in effective weight loss strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of sleep restriction on weight loss outcomes associated with caloric restriction. Wang, X., Sparks, JR., Bowyer, KP., et al.[2023]

Reduced sleep duration and quality are linked to hormonal imbalances that can increase the risk of obesity and type 2 diabetes, as sleep loss affects hormones like leptin and ghrelin that regulate appetite and energy expenditure.

The decline in average sleep duration over the past 50 years correlates with rising obesity rates, suggesting that improving sleep could be a crucial public health strategy to combat metabolic syndrome and related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic consequences of sleep and sleep loss. Van Cauter, E., Spiegel, K., Tasali, E., et al.[2022]

Chronic partial sleep loss is linked to an increased risk of obesity and diabetes, as it negatively affects glucose regulation and insulin sensitivity, leading to a higher likelihood of developing diabetes.

Sleep deprivation disrupts appetite regulation by decreasing leptin (which signals fullness) and increasing ghrelin (which promotes hunger), potentially causing individuals to misinterpret their energy needs and leading to overeating.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between sleep loss and increased risk of obesity and diabetes. Knutson, KL., Van Cauter, E.[2022]

Reduced sleep duration is linked to metabolic and hormonal changes that can lead to obesity, including decreased insulin sensitivity and increased hunger hormones like ghrelin.

The review emphasizes the importance of adequate sleep for maintaining metabolic health, suggesting that sleep curtailment may contribute to the rising rates of obesity, although further research and intervention studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short sleep duration and obesity: mechanisms and future perspectives. Zimberg, IZ., Dâmaso, A., Del Re, M., et al.[2012]

Partial sleep deprivation, defined as sleeping less than 6 hours per night, is linked to weight gain due to its negative impact on appetite-regulating hormones, increasing ghrelin and decreasing leptin, which can lead to higher energy intake.

While energy expenditure may not significantly change with partial sleep deprivation, it can lead to undesirable body composition changes, resulting in a greater loss of fat-free mass compared to fat mass, highlighting the importance of sufficient sleep for effective weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial sleep deprivation and energy balance in adults: an emerging issue for consideration by dietetics practitioners. Shlisky, JD., Hartman, TJ., Kris-Etherton, PM., et al.[2022]

Sleep restriction for 5 nights significantly impairs insulin sensitivity and the dynamic response of nonesterified fatty acids (NEFAs) during glucose metabolism, indicating a negative impact on metabolic health.

Two nights of recovery sleep were insufficient to fully restore insulin sensitivity and glycemic health, suggesting that chronic sleep deprivation has lasting effects on metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two nights of recovery sleep restores the dynamic lipemic response, but not the reduction of insulin sensitivity, induced by five nights of sleep restriction. Ness, KM., Strayer, SM., Nahmod, NG., et al.[2020]

Prolonged sleep restriction combined with circadian disruption, as experienced by shift workers, negatively impacts glucose regulation and metabolism, leading to increased plasma glucose levels after meals.

After a recovery period of 9 days with adequate sleep and circadian re-entrainment, metabolic parameters returned to normal, suggesting that proper sleep and circadian alignment are crucial for maintaining healthy metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Buxton, OM., Cain, SW., O'Connor, SP., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Update on energy homeostasis and insufficient sleep. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Influence of sleep restriction on weight loss outcomes associated with caloric restriction. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Association of sleep time with diabetes mellitus and impaired glucose tolerance. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Epidemiological evidence for the links between sleep, circadian rhythms and metabolism. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Metabolic consequences of sleep and sleep loss. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Associations between sleep loss and increased risk of obesity and diabetes. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Short sleep duration and obesity: mechanisms and future perspectives. [2012]

8. United States pubmed.ncbi.nlm.nih.gov

Partial sleep deprivation and energy balance in adults: an emerging issue for consideration by dietetics practitioners. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Two nights of recovery sleep restores the dynamic lipemic response, but not the reduction of insulin sensitivity, induced by five nights of sleep restriction. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. [2022]