Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT00194259 |
| Other study ID # |
HL70301 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
September 13, 2005 |
| Last updated |
March 5, 2014 |
| Start date |
August 2001 |
| Est. completion date |
June 2014 |
Study information
| Verified date |
January 2008 |
| Source |
Temple University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial Summary
This study will assess the effects of weight loss on sleep-disordered breathing (SDB) in 120
obese, type 2 diabetics with obstructive sleep apnea (OSA) from four Look AHEAD sites.
Changes in SDB will be compared between subjects randomized to weight loss (Lifestyle
Intervention Group) versus non-weight loss (Diabetes Education and Support Group) conditions
within the context of the Look AHEAD Study. Weight loss is frequently recommended for obese
patients with OSA, but the empirical foundation for this recommendation is not well
substantiated. Weight loss in obese apneics improves but does not eliminate SDB. Moreover,
the degree of improvement is not correlated with the amount of weight loss. This study will
assess SDB before treatment and at 1 and 2 years. We will also investigate clinical measures
of fat distribution that may mediate the non-linear relationship between weight loss and
improvements in SDB. Finally, we will examine the role of SDB in mediating changes in blood
pressure associated with weight loss.
Description:
The duration of the study is 5 years; participants will be enrolled in the study for a total
of 2 years. Recruitment will be based on the protocol set forth in the larger Look AHEAD
trial that will occur in 8 treatment waves, spaced approximately 4 months apart. Each of
these waves at the Penn site will include 40 people, making the potential subject pool
approximately 320 persons.
Participants at the Penn site will be approximately 44 men and women, between 45 and 75
years of age, with a body mass index (BMI) > 25 kg/m2. All subjects will be obese type 2
diabetics who have been randomly assigned to the Lifestyle Intervention Group or the
Diabetes Education and Support Group in the Look AHEAD Study. Therefore, the inclusion and
exclusion criteria are determined by the parent study. Patients who are currently being
treated for OSA (e.g., continuous positive airway pressure) or who have had surgical
treatment for OSA will be excluded. Patients who have been previously diagnosed with OSA but
are not being treated will be included. These 44 individuals represent a subset of the
approximately 320 persons who will be treated at the University of Pennsylvania site.
As part of the baseline visit (before randomization) for the Look AHEAD study, Look AHEAD
participants will be asked to sign a consent form for screening. Consenting participants
will complete the Multivariate Apnea Prediction Form. The MAP includes weight, height, age
and 3 questions about sleep-related symptoms. After the prescreen consent has been
completed, the Research Coordinator will invite the participant to complete the consent form
for this study. Interested subjects will be scheduled to meet with this study's Research
Coordinator during the subject's next scheduled Look AHEAD visit. Participants wishing to
enroll will undergo the baseline assessments and be scheduled for their baseline sleep
study. Subjects will be paid $50 for this sleep assessment. After completion of the baseline
sleep study, the results will be analyzed. Thirty subjects with a baseline RDI > 15 and 28
subjects with an RDI between 5 and 15 (5 < RDI < 15) will continue in the study, undergoing
the same assessments at years 1 and 2.
Obstructive sleep apnea (OSA) is a syndrome characterized by frequent cessations of airflow
during sleep (despite continued respiratory effort) that are caused by the closure of the
pharyngeal airway. The most frequently used metric to describe OSA is the respiratory
disturbance index (RDI) (sometimes referred to as the apnea-hypopnea index or AHI). RDI is
defined as the average number of apnea/hypopnea events per hour of sleep. The medical
consequences of OSA include an increased risk of hypertension, stroke, myocardial
infarction, and premature mortality. The behavioral and psychosocial consequences of OSA
include excessive daytime sleepiness, depression, sexual dysfunction, and a 3-7 fold
increase in the risk of motor vehicle accidents. Among 30 to 60 year olds, 9% of women and
24% of men in the general population have an RDI > 5. The serious consequences and high
prevalence of OSA clearly constitute a major public health problem.
OSA is strongly related to obesity, an important public health problem in its own right. In
a series of 1000 OSA patients, two thirds had body weights > 30% above recommended. Several
studies have identified body mass index (BMI) as the strongest predictor of RDI. Data from
the Wisconsin Sleep Cohort Study revealed that a one standard deviation increase in BMI was
associated with a four-fold increase in the risk of having an RDI > 5. Among obese patients
seeking weight loss treatment, nearly 40% exhibited evidence of SDB, and 10% required
treatment for OSA. The link between obesity and SDB is further supported by data showing
that weight loss significantly improves SDB in obese patients with OSA. Perhaps the most
compelling data about the effects of weight change on SDB, particularly weight gain, come
from a very recent study of the Wisconsin Sleep Cohort that examined changes in weight and
SDB over 4 years in a community sample of 690. On average, the sample experienced a 3 kg
weight gain and 1.4/hr increase in RDI. Across the entire sample, on average, a 1% change in
body weight was associated with a 3% change in RDI. Participants who reduced body weight by
10% experienced a 26% reduction in RDI, while those who increased body weight by 10%
experienced a 32% increase in RDI. A 10% weight gain was associated with a 6-fold increase
in the risk of developing a RDI > 15. These descriptive, longitudinal data are suggestive of
the benefits of weight loss on SDB, but several factors limit conclusions about the effects
of weight loss on obese OSA patients. First, the initial mean RDI was 4.1, so very few
subjects (n = 46) had moderate or severe OSA (RDI > 15). Further, only a small number of
subjects (n = 61) lost > 5% of initial body weight. Finally, similar to the broader
literature on the effects of weight loss, this study is limited by the lack of a no-weight
loss control group and the inability to distinguish intentional from non-intentional weight
loss.
Weight loss is a frequently recommended treatment for obese patients with OSA, but the data
to support this recommendation are not available. The lack of randomized trials, the study
of predominantly male samples, and the absence of follow-up evaluations leave physicians and
patients unsure about the clinical utility of weight loss for obese OSA patients. This study
will assess the effects of weight loss on sleep-disordered breathing (SDB) in obese, type 2
diabetics with OSA (RDI > 15) who will be randomly assigned to the Lifestyle Intervention
Group or the Diabetes Education and Support Group conditions as part of the larger Look
AHEAD trial. Our assessment of patients at baseline, and 1 and 2 years will allow us to
examine the relationship between weight change and SDB over time. We will also examine the
role of neck and abdominal fat distribution in mediating the effects of weight loss on SDB.
Finally, we will assess the impact of SDB in mediating changes in blood pressure associated
with weight loss.
All subjects will be obese type 2 diabetics who are enrolled in the larger Look AHEAD Study.
Fifty-eight subjects in total will be needed. Thirty of these subjects will have an RDI > 15
and 28 subjects will have an RDI of 5-14.9 and all will have been randomized to either the
Lifestyle Intervention Group or the Diabetes Education and Support Group.
All participants will complete the following assessments:
Nocturnal polysomnography (PSG). Overnight, unattended PSGs will be recorded in
participants' homes using the Compumedics' PS2 portable sleep system. Two sleep technicians
will go to the participant's home at 8:00-9:00 PM on the night of the PSG. A series of
calibrations will be performed and signal quality and sensor positions will be adjusted as
necessary. Before the technicians depart, the device will be set to activate 60 minutes
prior to the subject's intended bedtime. The subject will then be asked to sit quietly and
read or watch television for the duration of the time until lights out at his/her regular
bedtime. The next morning, the 2 sleep technicians will return to the participant's home to
remove the electrodes and sensors and to retrieve the equipment.
Neck circumference. Neck fat distribution will be estimated by a measurement of the neck
circumference at baseline and at 1 and 2 years by this study's Research Coordinator at the
Look AHEAD annual clinic visit. All measurements will be performed twice and recorded to the
nearest 0.1 cm.
Blood pressure. Blood pressure will be assessed at baseline and at years 1 and 2 in the
participant's home by the sleep technician. Measurements will be taken at night before the
equipment is attached and in the morning after the equipment has been detached. Since the
PSG is anchored to the participants usual sleep and wake schedule, we will obtain a morning
and evening blood pressure at approximately the same times of day. Blood pressure will be
measured in the dominant arm after 5 minutes of quiet rest in a seated position. Two
measurements, separated by 1 minute, will be performed and averaged.
Sagittal diameter. Sagittal diameter will be measured by the Holtain-Kahn Abdominal Caliper
at baseline and at 1 and 2 years by the Research Coordinator at the Look AHEAD annual clinic
visit. The measurement will be performed twice and recorded to the nearest 0.1 cm.
Questionnaires. Daytime sleepiness will be assessed by the Epworth Sleepiness Scale (ESS).
The ESS is a self-administered questionnaire measuring the general level of daytime
sleepiness. The ESS significantly distinguishes patients with and without OSA; a score above
10 is considered indicative of pathological sleepiness. Furthermore, it has been shown to
decrease for OSA patients treated with continuous positive airway pressure (CPAP). Quality
of life specific to sleep apnea will be assessed by the Functional Outcomes of Sleep
Questionnaire (FOSQ). The FOSQ is a measure assessing the impact of disorders of excessive
sleepiness on functional outcomes relevant to daily behaviors and quality of life. The FOSQ
reliably distinguishes apneics and controls and is sensitive to treatment effects. These
measures will be assessed at baseline and at 1 and 2 years by this study's Research
Coordinator at the Look AHEAD clinic visits and should take approximately 10 minutes to
complete.
Upper airway assessment. A brief (< 10 minutes) standardized clinical assessment of upper
airway and craniofacial features that distinguishes apneics and non-apneics will be
performed at baseline and at years 1 and 2 by the Research Coordinator.
Sleep log. Participants will be given a sleep log to keep for 7 days prior to their in-home
sleep study. Each morning when they wake up and each evening before going to bed they will
answer a few questions concerning the quality of their sleep and their daytime activities.
The procedures and treatments proposed in this study pose few known risks to subjects'
physical and psychological well-being. The requirements imposed upon participants for this
ancillary study pose no additional risks than those already present in the larger Look AHEAD
trial. There are no invasive measures associated with this study.
The benefits to the subjects studied in this research protocol, and to society at large, far
surpass the risks. Our study will provide valuable sleep assessments to a population at high
risk for sleep apnea, a significant benefit since most cases of SDB in the United States
(90%) are undetected. Furthermore, our study will offer both patients and their physicians
valuable information necessary in making subsequent decisions regarding the clinical
management of any SDB. The requirements imposed upon participants for this ancillary study
pose no additional risks than those already present in the larger Look AHEAD trial.
Although weight loss is a frequently recommended treatment for obese patients with OSA,
there has only been one randomized controlled trial including a no weight loss group.
Therefore, findings from this study will provide important information to society at large
in determining the effectiveness of weight loss treatment for OSA, a serious health problem.
Other known NCT identifiers
