Study participants are 18- to 50-year-old obese (BMI 30–55 kg/m2), sleep-deprived (average sleep less than 6½ h per night) men and pre-menopausal women (). By history we assess whether body weight has remained stable (within 5%) over the last 6 months. The participants are randomized into either the Intervention or the Comparison Group at a 2:1 ratio. Those in the Intervention Group are coached to increase their sleep gradually by at least 30–60 min, possibly up to a total of 7½ h per night. The Comparison Group is asked to continue its habitual short sleep habits. The study is divided into a 12-month Efficacy Phase followed by a 36-month Effectiveness Phase ().
Rationale behind inclusion/exclusion criteria
A 2–3 week run-in period permits assessment of compliance with study requirements (completing questionnaires, wearing devices) and the ability to increase sleep duration (Intervention Group) or maintain current sleep habits (Comparison Group). summarizes the inclusion/exclusion criteria.
Participants in both the Intervention and Comparison Groups are encouraged to follow the current standard of care for both exercise (60–90 min of activity daily) and diet. Drastic changes in daily routine in diet and exercise above current standards and/or previous existing individual habits are to be avoided. Participants are monetarily compensated for their time and compliance throughout the course of the study.
summarizes the non-pharmacological, educational and behaviorally based intervention designed to promote the extension of sleep duration. Each participant in the Intervention and Comparison Groups is given a personalized sleep plan based on an in-depth evaluation of current sleep habits at the beginning of the Efficacy Phase or Effectiveness Phase, respectively. The comprehensive sleep assessment includes several standardized sleep questionnaires. Individualized interventions designed to increase nightly sleep are prescribed, and participants are coached on how to gradually integrate these changes into their daily routine.
Behavioral modifications for extension of sleep duration. The recommendations are individualized to meet each participant’s needs and life-style
The study design is depicted in . At the time of randomization baseline measurements of resting energy expenditure, glucose tolerance and insulin resistance (oral glucose tolerance test), weight, BMI, quality of life, and vigilance are taken. These measurements are repeated at the end of the Efficacy Phase, the 12-month visit.
Figure 1 The different phases of the study are outlined in the figure, as they were originally planned. Of note, study duration has been extended to a total of 48 months (12 month, Efficacy, 36 month, Effectiveness). Participants are stratified by age and metabolic (more ...)
At the interim visits (1-, 2-, 4-, 6-, 8-, and 10-month visits), study progress is monitored in both groups through sleep evaluations, blood draws, and measurement of vital signs, weight, waist and neck circumferences. The Intervention Group is encouraged to continue individual sleep plans and compliance is evaluated and addressed. Adherence to behavioral recommendations to increase sleep duration is monitored through Actigraphy technology, self-reported sleep diaries, and vigilance testing (see ‘Monitoring Progress and Participant Compliance’ below). Although the Comparison Group is given less coaching, an effort is made to ensure that all participants are given an equal amount of time with the study physician, nurse, and clinicians.
The 12-month Efficacy Phase was designed to facilitate lifestyle change as well as monitor the effects of incremental sleep increase and capture substantial changes that have occurred over the course of a year of altered sleep habits.
All participants who complete the Efficacy Phase are eligible to participate in the Effectiveness Phase. The informed consent for this phase is obtained at the beginning of the Efficacy Phase, immediately after each participant has been randomized to the Intervention or to the Comparison Group. After they have completed the Efficacy Phase, participants from the Comparison Group are invited to increase sleep and are given the same coaching that their counterparts in the Intervention Group received 12 months earlier. The overall effectiveness of sleep education in a ‘real life’ setting is monitored, including the degree to which participants maintain or improve sleep habits. In addition, we will study the difference in the ability to increase sleep between the two groups, and whether regular coaching is a necessity for such a lifestyle change.
During the Effectiveness Phase, participants come to the clinic every 6 months for 3 years, where the same metabolic and vital measurements are assessed along with progress towards extension of sleep duration. Participants also are required to wear activity monitors, record weight and blood pressure, and fill out questionnaires online 1 week/month.
Monitoring progress and participant compliance
The following data elements are closely monitored throughout the course of the study: sleep time (by motion sensors and sleep questionnaires) (), estimated energy expenditure per day, weight, and hormone/lipid measurements associated with metabolic syndrome, vigilance, and mood. The study employs omni-directional accelerometers, a reliable, practical technology, allowing collection of data in an out-patient, real-life setting [24
]. The Actiwatch (Mini Mitter Co., Inc., Bend, OR), a small motion-sensing device worn on the wrist, records sleep duration activity over a 14-day period every month. Another device, called Actical, (Mini Mitter Co., Inc., Bend, OR), is worn on the participant’s hip for the same 14 days a month. This device also utilizes motion sensor technology, capturing the participant’s energy expenditure per day. Actical data reveals relative intensity and length of energy expenditure. Together with the participant’s height, weight, age, sex, and basal energy expenditure, this technology enables an acceptable estimate of total calories burned per day.
End-points and parameters assessed
Participant vigilance is monitored through the Psychomotor Vigilance Test, a widely accepted technology in the field of sleep research. This procedure, which is administered in the morning, involves the measurement of participant reaction time through a series of signal-response trials over a 10-min period. Completed at each visit, this test provides a measure of participant alertness, corroborating average sleep measurements.
Sample size, recruitment, and progress
The recruitment effort began in September 2006. summarizes the study timelines. The age range was chosen because the benefits of extension of sleep duration are better established in people less than 50 years old. Although studies are in progress to develop non-invasive methods of measuring biomarkers (such as amylase in the saliva [26
] that may give an indication of sleep needs on an individual basis), currently it is not possible to determine how much a participant is ‘sleep-deprived’ before the adverse outcomes are evident. Participants whose lifestyle is determined to undermine study compliance or who have medical conditions that may confound results are excluded.
One hundred and fifty participants are being recruited in the Baltimore-Washington metropolitan area. Newspaper and radio ads, flyers located across the NIH campus, and postings on clinical-trials.gov are the major modes of recruitment. In addition, advertising in local university newspapers, TV stations, and radios are used to reach the younger demographic population that has so far been more difficult to recruit. Since January 2007 we have randomized 109 participants; 76% are women, 62% are minorities, with an average age of 40.8 years and BMI of 38.5 kg/m2. Sleep duration at randomization was 40.3 h/week. As of January 2010, 28 Intervention and 22 Comparison participants had completed the Efficacy Phase. Most of the participants enrolled had never participated in a research study.
Sleep apnea is assessed when participants are admitted for randomization. Different from what originally planned (), for feasibility reasons so far we have not conducted polysomnography sleep studies. We have screened participants for sleep apnea by the use of an ambulatory device called ARES Unicorder (Advanced Brain Monitoring, Inc., Carlsbad, CA) that is considered a valid and low-cost alternative to traditional polysomnography [31
Because of a relatively good retention rate of ~70% over time, we have decided to extend the Effectiveness Phase from the original 6 months to a total of 36 months. During this 36-month period participants come for a brief visit every 6 months. During these visits the same measurements collected during the Efficacy Phase are repeated. Imaging studies for body composition, CT and DXA, are repeated every 12 months.
The secure database used in this study (created by Esprit Health), provides real-time study data. Management capabilities include a calendar of visits, as well as participants’ payment and contact information. ‘Esphere Online’ serves as a portal for engagement of participants in the study. In addition to serving as a resource for contact information and study procedures, participants also fill out questionnaires and self-reported sleep diaries and enter home measurement data online. Patients are encouraged to enter sleep information in a timely manner; an electronic time stamp provides documentation useful for monitoring. Online entry is believed to increase accuracy of self-reported sleep; use of paper sleep diaries introduces the possibility of retrospective completion. We will test whether maintaining regular contact with study participants improves and facilitates compliance with study requirements.