Obesity, Sleep, Sleep Restriction
Conditions
Keywords
Body Weight, Habitual sleep
Brief summary
The overall goal of this project is to look at the effects of long-term, sustained sleep restriction (SR) in adults, and assess the effects on mood and cognitive and physical performance.
Detailed description
Chronic Sleep Restriction (SR) is highly prevalent in today's modern society. Artificial light, portable electronic devices, and 24-h services have allowed individuals to remain active throughout the night, leading to reductions in sleep duration. SSD has been linked to obesity and our laboratory has been interested in establishing whether sleep could be a causal factor in the etiology of obesity. Given the increasing prevalence of obesity over the past 5 decades, coinciding with the marked reduction in sleep duration, further exploration into the role of sleep as a risk factor for obesity could provide additional ammunition in the fight to prevent further increases in the incidence of obesity. This study will be a randomized, crossover, outpatient SR study with 2 phases of 6 weeks each, with a 6 week wash-out period between the phases. Sleep duration in each phase will be the participant's regular bed- and wake times during the habitual sleep (HS) phase and HS minus 1.5 hours in the SR phase. During the HS phase, participants will be asked to follow a fixed bedtime routine based on their screening sleep schedule. During the SR phase, participants will be asked to keep their habitual wake time constant but delay their bedtime to achieve a reduction of 1.5 hours in total sleep time.
Interventions
BEHAVIORALSleep Restriction (SR)
Participants will be asked to keep their habitual wake time constant but delay their bedtime to achieve a reduction of 1.5 hours in total sleep time. A delay in bedtimes was chosen rather than advancing wake-up time because it most closely reflects differences in sleep timing behavior between short and normal sleepers.
Sponsors
NYU Langone Health
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 25-29.9 kg/m2 * Have at least one obese parent * Habitually sleep 7-9 hours a night * Free of any current and past sleep and psychiatric disorders, including eating disorders, diabetes or Cardiovascular disease (CVD) (i.e., normal scores on: Pittsburgh Quality of Sleep Questionnaire Epworth Sleepiness Scale, Berlin Questionnaire, Sleep Disorders Inventory Questionnaire, Beck Depression Inventory, Composite Scale of Morningness/Eveningness, Three Factor Eating Questionnaire) * All racial/ethnic groups
Exclusion criteria
* Smokers (any cigarettes or ex-smoker \< 3 years) * Neurological, medical or psychiatric disorder * Diabetics * Eating and/or sleep disorders * Contraindications for MRI scanning * Travel across time zones within 4 weeks * History of drug and alcohol abuse * Shift worker (or rotating shift worker) * Caffeine intake \> 300 mg/d * Heavy equipment operators * Commercial long-distance drivers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endpoint Fat Volume | Week 6 (endpoint) | Body composition (specifically fat volume) will be measured by MRI at baseline and endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ghrelin | 6 weeks | Average post-baseline values |
| Sedentary Behavior | Average over 6 weeks (measured daily) | Time spent in sedentary physical activity. |
| Leptin | 6 weeks | Average post-baseline values |
| Glucagon-like Peptide 1 | 6 weeks | Average post-baseline values |
| Orexin | 6 weeks | Average post-baseline values |
| Neuropeptide Y | 6 weeks | Average post-baseline values |
| Energy Expenditure (EE) | Measured over 14 days at the end of each phase (weeks 5 and 6; endpoint) | EE is the amount of energy (or calories) that a person needs to carry out physical functions and will be assessed using Doubly Labeled Water (DLW), during the last 2 weeks of each sleep phase. |
| Physical Activity | Average over 6 weeks (measured daily) | Time spent in moderate-to-vigorous physical activity. |
| Regional Brain Activation in Response to Food Stimuli | Week 6 | The primary aim of this outcome was to investigate brain activation in response to food stimuli after a six-week period of Adequate Sleep (AS) or mild Sleep Restriction (SR). To achieve this, the investigators contrasted neuronal responses to food and non-food stimuli at two time points (baseline and six weeks post-intervention/control). This contrast allowed the investigators to calculate the number of voxels activated during the view of food stimuli compared to the number of voxels activated during the view of non-food stimuli (food - non-food) under each condition (AS or SR). Regional brain activation is reported as the total number of voxels activated on the group contrast images (combination of all analyzed participants) of the neuronal response to food stimuli compared to non-food stimuli. For this analysis, voxels were considered activated if they survived Gaussian Random Field theory correction with a 2-tailed p \< 0.001 threshold when creating the group contrast images. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune Function | Week 5 (endpoint) | CD8+ T-cells from samples collected late in the day (non-fasted) |
| Immune Markers | Week 5 (endpoint) | Classical monocytes measured from samples collected late in the day (non-fasted) |
| Distance Walked | Week 5 | Distance walked over a 6-minute walk test |
| NIH Toolbox® | Week 6 (endpoint) | Working memory data were collected using the List Sorting Working Memory Test from the NIH Toolbox. Data were transformed into a t-score ranging from 0-100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data were collected at baseline and after 6 weeks on study intervention. Traditionally, a clinically relevant threshold for cognitive data is 1.5 standard deviations below the mean. For a t-score, this would mean that a score of 35 or lower suggests clinical relevance. |
| Neuro-behavioral Measures | Week 6 (endpoint) | Episodic verbal learning and memory were collected using the Modified Rey Auditory Verbal Learning Test (ModRey). The primary variable of interest for this test is the number of correctly recalled words across three learning trials from List A consisting of 20 words in each trial. The total score range across three trials is 0-60. A higher score indicates better performance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adequate Sleep Followed by Sleep Restriction Participants were randomized to continue adequate sleep in phase 1 and crossed over to sleep restriction condition in phase 2 | 22 |
| Sleep Restriction Followed by Adequate Sleep Participants were randomized to restrict sleep in phase 1 and crossed over to follow their habitual adequate sleep in phase 2 | 23 |
| Total | 45 |
Baseline characteristics
| Characteristic | Adequate Sleep Followed by Sleep Restriction | Sleep Restriction Followed by Adequate Sleep | Total |
|---|---|---|---|
| Age, Continuous | 32.5 years STANDARD_DEVIATION 12.3 | 31.6 years STANDARD_DEVIATION 11.4 | 32.0 years STANDARD_DEVIATION 11.7 |
| Body fat volume by MRI | 23.9 Liter STANDARD_DEVIATION 10.1 | 24.6 Liter STANDARD_DEVIATION 11.4 | 24.3 Liter STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 16 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 7 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Ghrelin | 870.3 pg/mL STANDARD_DEVIATION 341.5 | 750.5 pg/mL STANDARD_DEVIATION 251 | 810.4 pg/mL STANDARD_DEVIATION 302.1 |
| Glucagon-like peptide 1 | 25.0 pM STANDARD_DEVIATION 13.1 | 21.5 pM STANDARD_DEVIATION 11 | 23.2 pM STANDARD_DEVIATION 12.1 |
| Leptin | 21.9 ng/mL STANDARD_DEVIATION 19.3 | 26.5 ng/mL STANDARD_DEVIATION 19.9 | 24.3 ng/mL STANDARD_DEVIATION 19.5 |
| Neuropeptide Y | 1.37 ng/mL STANDARD_DEVIATION 0.68 | 1.32 ng/mL STANDARD_DEVIATION 0.68 | 1.34 ng/mL STANDARD_DEVIATION 0.67 |
| Orexin | 1.34 ng/mL STANDARD_DEVIATION 0.52 | 1.21 ng/mL STANDARD_DEVIATION 0.48 | 1.28 ng/mL STANDARD_DEVIATION 0.5 |
| Physical Activity | 103.6 minutes/day STANDARD_DEVIATION 49.5 | 89.3 minutes/day STANDARD_DEVIATION 41.7 | 96.7 minutes/day STANDARD_DEVIATION 46.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 13 Participants | 8 Participants | 21 Participants |
| Region of Enrollment United States | 22 participants | 23 participants | 45 participants |
| Sedentary Behavior | 741 minutes/day STANDARD_DEVIATION 94 | 752.4 minutes/day STANDARD_DEVIATION 93.4 | 746.4 minutes/day STANDARD_DEVIATION 93.8 |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 39 |
| other Total, other adverse events | 0 / 42 | 0 / 39 |
| serious Total, serious adverse events | 0 / 42 | 0 / 39 |
Outcome results
Primary
Endpoint Fat Volume
Body composition (specifically fat volume) will be measured by MRI at baseline and endpoint.
Time frame: Week 6 (endpoint)
Population: Data were available from 38 women who underwent MRI scanning for body composition assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Endpoint Fat Volume | 24.0 Liter | Standard Deviation 11.4 |
| Sleep Restriction (SR) | Endpoint Fat Volume | 24.2 Liter | Standard Deviation 11.6 |
Secondary
Energy Expenditure (EE)
EE is the amount of energy (or calories) that a person needs to carry out physical functions and will be assessed using Doubly Labeled Water (DLW), during the last 2 weeks of each sleep phase.
Time frame: Measured over 14 days at the end of each phase (weeks 5 and 6; endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Energy Expenditure (EE) | 2445 kcal/d | Standard Deviation 548 |
| Sleep Restriction (SR) | Energy Expenditure (EE) | 2476 kcal/d | Standard Deviation 527 |
Secondary
Ghrelin
Average post-baseline values
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Ghrelin | 856.6 pg/mL | Standard Deviation 325.7 |
| Sleep Restriction (SR) | Ghrelin | 819.4 pg/mL | Standard Deviation 287.2 |
Secondary
Glucagon-like Peptide 1
Average post-baseline values
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Glucagon-like Peptide 1 | 22.9 pM | Standard Deviation 9.7 |
| Sleep Restriction (SR) | Glucagon-like Peptide 1 | 23.0 pM | Standard Deviation 11.1 |
Secondary
Leptin
Average post-baseline values
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Leptin | 23.4 ng/mL | Standard Deviation 18.9 |
| Sleep Restriction (SR) | Leptin | 23.5 ng/mL | Standard Deviation 19.2 |
Secondary
Neuropeptide Y
Average post-baseline values
Time frame: 6 weeks
Population: Assay run on a sub-set of participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Neuropeptide Y | 1.36 ng/mL | Standard Deviation 0.7 |
| Sleep Restriction (SR) | Neuropeptide Y | 1.41 ng/mL | Standard Deviation 0.67 |
Secondary
Orexin
Average post-baseline values
Time frame: 6 weeks
Population: Assays were run on a sub-set of participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Orexin | 1.29 ng/mL | Standard Deviation 0.61 |
| Sleep Restriction (SR) | Orexin | 1.34 ng/mL | Standard Deviation 0.62 |
Secondary
Physical Activity
Time spent in moderate-to-vigorous physical activity.
Time frame: Average over 6 weeks (measured daily)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Physical Activity | 86.1 minutes/day | Standard Deviation 48.1 |
| Sleep Restriction (SR) | Physical Activity | 87.4 minutes/day | Standard Deviation 43.4 |
Secondary
Regional Brain Activation in Response to Food Stimuli
The primary aim of this outcome was to investigate brain activation in response to food stimuli after a six-week period of Adequate Sleep (AS) or mild Sleep Restriction (SR). To achieve this, the investigators contrasted neuronal responses to food and non-food stimuli at two time points (baseline and six weeks post-intervention/control). This contrast allowed the investigators to calculate the number of voxels activated during the view of food stimuli compared to the number of voxels activated during the view of non-food stimuli (food - non-food) under each condition (AS or SR). Regional brain activation is reported as the total number of voxels activated on the group contrast images (combination of all analyzed participants) of the neuronal response to food stimuli compared to non-food stimuli. For this analysis, voxels were considered activated if they survived Gaussian Random Field theory correction with a 2-tailed p \< 0.001 threshold when creating the group contrast images.
Time frame: Week 6
Population: fMRI data was collected from 26 participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Habitual Sleep (HS) | Regional Brain Activation in Response to Food Stimuli | 469 Activated Voxels |
| Sleep Restriction (SR) | Regional Brain Activation in Response to Food Stimuli | 218 Activated Voxels |
Secondary
Sedentary Behavior
Time spent in sedentary physical activity.
Time frame: Average over 6 weeks (measured daily)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Sedentary Behavior | 766.9 minutes/day | Standard Deviation 106.5 |
| Sleep Restriction (SR) | Sedentary Behavior | 851 minutes/day | Standard Deviation 87.6 |
Other Pre-specified
Distance Walked
Distance walked over a 6-minute walk test
Time frame: Week 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Distance Walked | 620.2 meters | Standard Deviation 81.1 |
| Sleep Restriction (SR) | Distance Walked | 625.7 meters | Standard Deviation 85.2 |
Other Pre-specified
Immune Function
CD8+ T-cells from samples collected late in the day (non-fasted)
Time frame: Week 5 (endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Immune Function | 102212 cells/mL | Standard Deviation 88785 |
| Sleep Restriction (SR) | Immune Function | 107844 cells/mL | Standard Deviation 259554 |
Other Pre-specified
Immune Markers
Classical monocytes measured from samples collected late in the day (non-fasted)
Time frame: Week 5 (endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Immune Markers | 80038 cells/mL | Standard Deviation 41470 |
| Sleep Restriction (SR) | Immune Markers | 134056 cells/mL | Standard Deviation 59315 |
Other Pre-specified
Neuro-behavioral Measures
Episodic verbal learning and memory were collected using the Modified Rey Auditory Verbal Learning Test (ModRey). The primary variable of interest for this test is the number of correctly recalled words across three learning trials from List A consisting of 20 words in each trial. The total score range across three trials is 0-60. A higher score indicates better performance.
Time frame: Week 6 (endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | Neuro-behavioral Measures | 33.8 score | Standard Deviation 8.7 |
| Sleep Restriction (SR) | Neuro-behavioral Measures | 33.5 score | Standard Deviation 9.5 |
Other Pre-specified
NIH Toolbox®
Working memory data were collected using the List Sorting Working Memory Test from the NIH Toolbox. Data were transformed into a t-score ranging from 0-100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data were collected at baseline and after 6 weeks on study intervention. Traditionally, a clinically relevant threshold for cognitive data is 1.5 standard deviations below the mean. For a t-score, this would mean that a score of 35 or lower suggests clinical relevance.
Time frame: Week 6 (endpoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Habitual Sleep (HS) | NIH Toolbox® | 57.2 T-score | Standard Deviation 6.5 |
| Sleep Restriction (SR) | NIH Toolbox® | 50.8 T-score | Standard Deviation 7.9 |