Design paperThe DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression
Section snippets
Background and aims
Depression is a prevalent illness (17% lifetime prevalence) [1] with a high cost to society (estimated $44 billion/year) [2] and to the quality of life of the individual 3, 4. The Global Burden of Disease study [5] found that in developed nations unipolar major depression ranks second behind ischemic heart disease in lost years of healthy life due to premature death or disability. Current estimates indicate that only 25% of adults suffering from depression seek treatment despite major advances
Specific objectives
There were two major objectives of the DOSE study. The first was to determine the efficacy of aerobic exercise as a sole treatment of mild to moderate MDD in participants randomized to exercise compared with an “equal contact” exercise placebo control group over a 12-week acute phase treatment. The second objective was to determine the dose-response relation between different amounts and frequencies of aerobic exercise with the reduction of depressive symptoms. We hypothesized that the active
Participant selection criteria
We recruited men and women between the ages of 20 to 45 years with mild to moderate MDD. The HRSD score for mild depression is 12 to 16 and for moderate depression 17 to 25 [17]. The choice of age group was made for both scientific and practical reasons. The scientific literature suggests that MDD usually begins when individuals are 20 to 30 years of age, although it can begin at any age [18]. Also, visit rates to psychiatrists are the highest for the 20- to 40-year age group, and the
Primary outcomes
The HRSD-17 (17 items) is a clinician-rated measure designed to assess the severity of depression by assessing both the intensity and frequency of depressive symptoms. This is the most widely used measure of depression severity for clinical trials research. One review published in 1996 reported it was used in 500 published studies over a 10-year period [21], using the Cronbach α=0.88 for internal consistency. Others have found the HRSD to be correlated with psychiatrists' global rating (r
Trial design
The design of this study was a 2×2 factorial design with an exercise placebo as the control group. The two exercise factors manipulated in this design were total weekly energy expenditure per kilogram of body weight (7 kcal/kg/week and 17.5 kcal/kg/week) and frequency of exercise (3 days/week or 5 days/week). Therefore, for a 70-kg person, the total weekly energy expenditure would be 490 kcal/week if he or she received the 7 kcal/kg/week dose or 1225 kcal if he or she received the 17.5
Recruitment and screening procedures
We used a combination of recruitment techniques based, in part, on recommendations from The Cooper Institute Community Advisory Board. This included media stories on television and in the newspaper, mass mailings, letters to churches and physicians, community health fairs, and flyers distributed to businesses such as grocery stores, libraries, and apartment buildings.
Size of the trial and statistical power
We anticipated that HRSD-17 scores at baseline would have a mean of 20 points and standard deviation of seven points 49, 50, 51, 52, 53. Clinically meaningful and important treatment effects would reduce HRSD scores ⩾50%, a score of ten or less. Without preliminary data for within-individual correlation of HRSD scores pre- and postintervention, statistical power was conservatively based on comparing postintervention scores. Power for comparing active treatments with control was based on the
First 12 weeks: supervised exercise
Following randomization, all participants exercised under supervision at our laboratory for the first 12 weeks of the treatment study. Weight (kg) was collected weekly to calculate the weekly exercise dose. Participants were allowed to use a treadmill (Technogym RUNRACE) or stationary bicycle (Technogym BIKERACE) and wore a Polar Vantage XL heart- rate monitor during each exercise session. Data from the heart-rate monitor were downloaded into the exercise database. If participants used the
Data collection
Table 2 shows a summary of all data collection and time points for the DOSE study beginning with the telephone prescreen.
Data management and quality control
The data management group at The Cooper Institute oversees all data collection. Manually entered data was double-keyed and verified for accuracy, using on-screen database forms that match the format of paper forms, programmed with appropriate skip patterns and range and logic checks. Scannable data forms were reviewed prior to processing to ensure marks were clear and dark
Plans for statistical analyses
To assess the effectiveness of randomization, we will tabulate mean baseline levels of the HRSD and IDS scores among randomized participants by treatment assignment, along with age, gender, body mass index (BMI), energy expenditure, resting heart rate, blood pressures, predicted exercise capacity, medical history, and psychosocial measures. Characteristics of randomized participants who refuse treatment, drop out before completing acute-phase treatment, or complete treatment will be tabulated
Discussion
The DOSE study is the first study to our knowledge to manipulate the dose of exercise in a group of participants stringently diagnosed with mild to moderate MDD. The high internal validity of the study will allow us to assess whether exercise could be an efficacious treatment for these individuals and to identify what dose of exercise is necessary for treatment. Randomization of participants started in August 1998, and treatments were completed in October 2001. The recruitment to randomization
Acknowledgements
Participating institutions: The Cooper Institute, Dallas, Texas, USA; The University of Texas Southwestern Medical Center Depression and Anxiety Disorders Program, Dallas, Texas, USA. Steering Committee: Andrea L. Dunn, Madhukar H. Trivedi, Heather O. Chambliss.
We wish to thank participants in the DOSE study; The Cooper Institute Scientific Advisory Board: Claude Bouchard, William L. Haskell, Norman M. Kaplan, I-Min Lee, Kiang Liu, Guy S. Parcel; The Cooper Institute Community Advisory Board:
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