This is a randomized controlled trial where obese participants with MDD are randomized to one of two treatment conditions: BA or ST. All procedures and material were approved by the University of Massachusetts Medical School's Internal Review Board.
Women between the ages of 21 and 65 years old who meet criteria for obesity and MDD will be recruited. Table summarizes the inclusion and exclusion criteria. Exclusion criteria were derived to: 1) minimize adverse effects of the intervention (e.g., physical limitations, does not receive physician clearance); 2) decrease error associated with the primary outcomes (e.g., taking weight loss medication or medications that influence weight); 3) prevent missing data (e.g., plans to move, no telephone) and 4) prevent participants who may require more intensive or more appropriate psychological intervention from enrolling in the study (e.g., active suicidal ideation, bipolar disorder, psychotic disorder). Participants who have been taking antidepressant medications (ADM) for more than 3 months and have no plans to change the regimen will be eligible. While participants who are on ADM will not be excluded, those in psychotherapy will be excluded because of potential conflicting therapeutic goals and possible contamination in the no therapy condition.
Participant eligibility and exclusion criteria.
A computerized Patient Health Care Information System used in the University of Massachusetts Memorial (UMM) primary care clinics will identify participants who are potentially eligible using age, female gender, and body mass index ranges. Candidates will be contacted via an introductory letter signed by their primary care physician and the principal investigator (PI). Candidates will be given the opportunity to opt out by phone, or be phoned for an initial telephone screening two weeks after receiving the letter. Participants will also be recruited from the community via media outlets, the medical center intranet, and community flyers. Minority populations will be targeted by distributing flyers to businesses and health clinics that serve predominately minority populations and using advertisements in media outlets that have a large minority audience base. Free seminars about women's health will also be conducted at local businesses, community organizations, and churches to facilitate recruitment.
Screening Process and Informed Consent
Initial eligibility will be assessed by phone and pre-eligible participants will be invited to the study visit for a screening appointment where informed consent will be obtained and eligibility will be further assessed. The Structured Clinical Interview for the Diagnostic and Statistical Manual-IV [20
] will be administered to confirm the diagnosis of MDD. Eligible participants will then complete a baseline assessment visit, for which they will receive $50 (see Table for the list of screening and baseline measures). Those not qualifying will receive referrals to weight loss and/or depression treatment, when applicable.
List of measures and frequency.
After completing the baseline visit and 24 hour diet and physical activity recalls, participants will be randomized to the BA or ST condition. Participants will be stratified into 4 strata of possible combinations of ADM (2: present, absent) × MDD severity (2: Hamilton Rating Scale for Depression (HRSD); [21
]: 13–18, 19–24) at baseline. Within each strata, participants will be randomized to the two conditions in randomly permuted blocks of size 3 and 6 using the ralloc program in Stata [22
]. This will ensure that the distribution of ADM status and MDD severity are approximately similar between two study conditions.
Outcomes and Study Measures
The main study outcome will be body weight measured using the digital Tronix scale, with the participant wearing only light clothing and no shoes. Body weight will be measured at every study visit, but analyses will focus primarily on change in body weight from baseline to the 6-months and 1- and 2-year follow-up.
Secondary outcomes include depression (HRSD and Beck Depression Inventory-II (BDI-II); [23
]), physical activity and dietary intake, other psychosocial variables (emotional eating, quality of life), and cardiovascular risk factors (blood pressures, serum lipids, C-reactive protein) at 6-months and 1- and 2-year follow-up.
Treatment adherence data will also be collected at all assessment time points to examine possible mechanisms of the effect of the BA intervention on body weight. Additional potential mediators include caloric intake, physical activity and depression (see Table for a complete list of study measures and the timing of these measures).
Both ST and BA conditions will involve an Intensive Treatment and a Maintenance phase. The Intensive Treatment phase will last 6-months and involve 26 sessions. Ten sessions will be 1-hour individual visits, and 16 sessions will be 1.5-hour group behavioral weight loss visits conducted by a registered dietitian or exercise physiologist. The timing of the individual and group visits varies between the two conditions. In the BA condition, participants will begin with 10 weekly individual visits of behavior therapy for treatment of depression, with the initial group behavioral weight loss visits starting on week 9. Participants in the ST condition will begin both the group behavioral weight loss visits and individual health education visits on week 1 (see Tables and for the timing of individual and group sessions in each condition) for two reasons. First, paralleling the BA condition (i.e., first 8-weeks of individual visits of health education attention control only) could lead to differential attrition rates since ST participants may not stay engaged when active treatment is delayed for 8 weeks. Second, this approach is also more consistent with usual care, in which participants would be enrolled and begin treatment immediately.
Distribution of treatment sessions by condition during the first 12 weeks of the 6-month Intensive Treatment phase.
Distribution of treatment sessions by condition during the second 12 weeks of the 6-month Intensive Treatment phase.
The 18 month Maintenance phase will consist of 6 monthly 90-minute group sessions and 6 monthly 20-minute counseling phone calls by their therapist or health education counselor, depending on their condition assignment. Then, participants will receive 20-minute counseling phone calls once every 3 months for one year. All visits in both phases will be audiotaped for quality assurance.
Behavioral Weight Loss
Behavioral weight loss groups will be based on the Diabetes Prevention Program (DPP) [24
]. A team dietitian will lead 8 of the 16 Intensive Treatment sessions and 3 of the 6 Maintenance sessions. During the Intensive Treatment phase, participants will receive extensive instruction and practice in self-monitoring of caloric and fat intake. Participants will receive calorie goals that are estimated to produce a weight loss of 1–2 pounds per week [i.e., (starting weight × 12) – 500 kcal]. All participants will be given a goal for daily total fat intake in grams that is based on 25% of total calories from total fat. Participants will self-monitor fat and calories daily for 18 weeks and then one week every month for the following 6-months. Participants will be encouraged to work slowly toward regular self-monitoring, beginning with 2–3 days and working up to 5–7 days over the first 16 weeks. Participants who have difficulty tracking their dietary intake and physical activity will be given modest goals with suggestions to increase tracking gradually. Participants will receive assistance to individualize the study diet based on their usual dietary habits. Participants will be given diet diaries for self-monitoring, the "DPP Fat Counter," a guide of nutrition information for hundreds of foods, and multiple resources for obtaining additional information on areas of concern, including eating out and other social activities and recipes. Self-monitoring diaries will be reviewed by the registered dietitian and returned with suggestions for change and positive feedback. Although the original DPP protocol is based on a low-fat diet, this has been updated to include suggestions to decrease detrimental fats preferentially, namely saturated and trans
-fats, and to substitute whole grains in place of refined carbohydrate foods to match current dietary recommendations put forth by the United States Department of Agriculture Dietary Guidelines for Americans and the American Heart Association Dietary Guidelines [25
The exercise physiologist will lead 8 of the 16 Intensive Treatment group sessions and 3 of the 6 Maintenance sessions. Participants will work toward the goal of 60 minutes of moderate physical activity on 5 days/week. While walking will be encouraged and pedometers provided, participants will also be encouraged to increase their engagement in any of their preferred physical activities. Participants will be lead through a brief moderate physical activity in each session following didactic content. Examples include group walks, pilates, aerobics, and yoga. See Table for the complete list of group topics.
Content of group sessions during Intensive Treatment (16 sessions) and Maintenance (6 monthly sessions) phases.
The treatment protocol for individual sessions is based on brief behavioral activation treatment as developed by Lejuez and colleagues [14
]. Each session will emphasize behavioral activation strategies for depression and how the behavioral activation approach can lead to a more enriching active lifestyle (See Table for individual session content) [14
]. A Master's or doctoral level counselor will conduct all 10 of the individual counseling sessions and all 10 of the 20-min telephone sessions. A total of 20 sessions (in person and telephone) are devoted to behavioral activation strategies because efficacy with this protocol has been established in 20–24 sessions [28
Content of behavioral activation individual sessions during Intensive Treatment phase.
Participants will first be educated about how depression affects them from a behavioral activation perspective. Then, the following behavioral activation skills will be taught: 1) self-monitoring of daily activities and moods; 2) identification of relationships between daily activities and mood; 3) behavioral contracting; 4) identification of values and goals within a variety of life areas including relationships, employment/career, hobbies/recreation, physical/health issues, and spirituality; 5) developing an activity hierarchy in which 15 activities consistent with life goals are rated ranging from "easiest" to "most difficult" to accomplish; 6) regular completion of a master activity log and behavioral checkout to monitor progress as the participant moves through the hierarchy in a progressive manner, moving from the easier behaviors to the more difficult; 7) recognition of avoidance patterns and how they affect mood; and 8) continued assessment of progress and modification of goals as necessary. Earlier sessions will be used to introduce these components and later sessions will include both strategies for increasing success in achieving reasonable life activity goals and for modifying unrealistic or overly difficult activity goals. Behavioral activation for depression is not meant to specifically target weight loss as a goal. Instead, it will address the processes underlying weight dysregulation, including mood regulatory eating, avoidance, and inactivity. Addressing these factors in advance of dietary and physical activity prescriptions may be essential to progress toward weight loss goals during the weight treatment program that follows.
During the Maintenance phase, counselors will contact participants monthly for 20-min phone calls for 6-months and quarterly for one year. As Lejuez and colleagues [14
] describe, once participants have progressed to become more skilled at behavioral activation, sessions may become shorter and/or administered by phone. Phone contacts will be used to provide support for continued progress, reinitiate self-monitoring, recycle through the activation process when needed, and keep contact information up-to-date.
Behavioral Weight Loss
Although the timing of the group visits will differ between conditions, the content of the group weight loss intervention in the ST condition will be identical to the BA condition as described above.
Attention Control (Health Education)
A health educator with no training in behavior therapy or psychological counseling will conduct all 10 individual sessions during the Intensive Treatment phase and all 20-minute phone calls during the Maintenance phase. Health education sessions were added to the ST condition to serve as an attention control for the nonspecific effects of behavior therapy. An attention control is designed to simulate a behavioral intervention, providing the same amount of contact as the individual counseling in the BA condition, but is not believed to be an effective treatment for depression [30
]. This attention control condition lacks components of behavioral activation that are considered integral to its success. The content of the attention control sessions is designed based on prior research demonstrating that provision of information is not sufficient to change behavior [31
]. Health information about topics relevant to women's health will be discussed. Participants will select from 19 different health education and well-being topics including body composition analyses, menopause, skin health, finances, dressing for different body shapes, and proper footwear (see Table for the full list of topics). To enhance attendance, participants will be informed that the visit will be for a "weigh in" and health education counseling. The health educator will develop a supportive relationship with the participant, provide health education, but will avoid problem solving or counseling with the participant for depression treatment. When participants have specific questions regarding goals or seek advice, they will be referred to their group leader.
List of topics for standard treatment individual sessions during Intensive Treatment phase.
During the Maintenance phase, health educators will contact participants monthly for 20-minute phone calls for 6 months and quarterly for one year. Calls will be for the purpose of fostering motivation to attend the 1- and 2-year follow-ups as well as to provide educational material on women's health issues.
All eligible participants must receive permission from their primary care physician to participate in the study. Depression safety precautions include having participants complete a BDI-II at every individual and group visit, (except when there is an individual and group visit in the same week) to assess depression levels and suicidality. If a participant reports active suicidal ideation with intent, she will be referred for psychiatric treatment and/or escorted to the Emergency Department at UMM. The PI, a licensed clinical psychologist, will review depression severity scores (BDI-II) of all participants on a weekly basis. If a participant's depression symptoms elevate to 30 or higher on the BDI-II (i.e., severe depression) during treatment, alternative treatment will be deemed clinically necessary and that participant will be referred to the appropriate service. Participants who remain depressed (BDI-II > 12) at the end of treatment will receive written materials about depression treatment options and a list of referrals for depression treatment services.
To minimize risks associated with increasing physical activity, intervention personnel will screen participants at each encounter point to assess symptoms that would increase the risk of physical activity and to report concerns as appropriate. In the case of a concern, the study physician and the participant's primary care physician will be consulted. The nutritional adequacy of the diet will be monitored by our senior nutritionist. If there is concern about a participant's nutrient intake, a report is sent to the participant's primary care physician with the area of concern highlighted and appropriate advice provided by our clinical nutritionist.
Safety monitoring procedures are documented in a standard protocol and overseen by the PI and project director. Any adverse events are reviewed by the study physician within 24 hours. If he deems that the adverse event warrants escalation, the data safety monitoring board (DSMB) will then be notified. Unanticipated adverse events or anticipated adverse events that require medical treatment will be reported to the internal review board. All adverse reactions reported by participants will be documented by intervention providers and reviewed on a monthly basis by the PI and project director. Participants will be referred to their healthcare provider for a medical evaluation and follow-up as needed or recommended by the DSMB. The internal review board, the funding agency and the DSMB will be notified of serious adverse events within 48 hours.
A participant tracking system will be used to assure that participants are contacted on a timely basis to obtain study data. Participants are also provided a $50 incentive at baseline, 6-months and 1- and 2-year follow-ups for completion of data collection visits. If they are unable to attend, a home visit will be arranged. Following a missed intervention class, participants will receive class materials by mail. Regular telephone contact with individual BA therapists and ST health educators (monthly during the last 6 months of year 1 and every three months during year 2) will help to keep participants engaged in the program and provide an opportunity to obtain updated contact information. If an individual therapist or health educator is concerned about a participant withdrawing, he or she will speak individually with the participant and attempt to address reasons for disengagement or drop-out. For the purposes of retention, at least three alternative contacts, individuals (e.g., family members, friends) who could provide the participant's contact information if it changes, are collected.
Sample Size Considerations and Statistical Analyses
This study will randomize 174 participants into two conditions (87 per condition) who will be followed for 2 years. We expect approximately 90% power for detecting differences in weight between the conditions assuming a weight change difference of 3.1 kg at 1-year (standard deviation = 5.5 kg) and a 25% loss-to-follow-up rate. This projected data for group differences was taken from pilot data at 6 months and projected to one year based on the original DPP weight change data. The standard deviation was a conservative value chosen from a range of successful lifestyle intervention studies [38
Primary and Secondary Hypotheses-Analysis Plan
The primary outcome compares body weight between the two randomized groups at 6-months and 1-year follow-up using an intent-to-treat analysis. Linear mixed modeling, using SAS PROC MIXED [41
] will test time and group interactions to asses whether within-subject change in body weight differs by condition. Analyses will also be conducted to examine whether there is a dose-response relationship between attendance and outcome, where dose is defined in terms of number of sessions attended. In addition, we will model percent change in body weight at 6-, and 12-months using a similar model.
Secondary outcomes will compare the conditions on depression scores, physical activity, daily caloric intake, treatment adherence (session completion), quality of life score, waist circumference, blood pressure, C-reactive protein and serum lipids at 6-months and 1- and 2-years. Analyses for these outcomes will be similar to those conducted for body weight. To explore proposed mechanisms of change, longitudinal associations of body weight and depressive scores, treatment adherence, and physical activity will be modeled using structural equation modeling [42
]. Reciprocal influences of body weight and other factors over time will be modeled in structural equation modeling using nonrecursive models [43
]. The two conditions will also be compared on body weight and secondary outcomes at the 2-year follow-up relative to baseline to examine long-term maintenance. The analysis for this outcome will be similar to those conducted for body weight at 6 months and 1-year.
Study Operation and Tracking System
The tracking system used for monitoring participant study activities and providing necessary prompts is based on a communication system using Lotus Notes software R5 from IBM (Release 5.0.11). Because of its responsiveness to changes in study participants' data, the Lotus Notes tracking system functions as a watchdog for the staff, automatically flagging any participant who is nearing a deadline for a measurement or intervention session. This system is ideal for monitoring the progress of study participants and interventionists, and alerts the project manager and other study personnel to all study data collection points. The software also will be used to gather and store data that can be shared by individuals both on-site and in remote locations. This includes 24 hour dietary and physical activity recall call assignments and the status of these and other data which are collected at remote sites and downloaded directly to the Lotus Notes system. It also provides reports of data such as those from participant questionnaires and blood test results. Storage of such data provides instant access to critical information for intervention and data collection. Multiple levels of password protection are utilized to ensure data security.
All study data are entered into computerized data files utilizing: 1) Lotus Notes for participant tracking and intervention data entry, 2) the Nutrition Data System for Research software computer-assisted telephone interview system for 24 hour recalls, and 3) Snap Surveys for double-entry verification of data from paper and pencil forms. Data sets will be cleaned, verified and archived, and then read into SAS (version 9.1) data sets, which also are archived. All analytic and tracking database files are stored in a secure network drive and backed up at daily basis. On a weekly, monthly, quarterly and yearly basis complete backups are made of all database files. One copy is saved on-site and one off-site. Separate archival databases are permanently maintained.
At the time of data collection, research assistants will review participant responses on questionnaires with participants present. Skipped or incorrectly addressed items will be brought to the participant to correct. Data from pencil and paper forms are entered using a double entry format. All of the data entry systems employ automatic checks for values that are out of range or represent errors of logic. These procedures reduce transcription errors for hard copy data to close to zero (<0.5%). A random 10% of all 24 hour recall telephone interviews will be monitored. Monthly exploratory analyses will be conducted to detect outliers [44
Individual Sessions (Behavioral Activation and Health Education)
Treatment fidelity checklists (2 Provider Checklists and 1 Auditor Checklist) were developed to monitor treatment fidelity. A set of Provider Checklists were developed for each condition. Interventionists will complete a Provider Checklist after each session. A random selection stratified by counselor of 10% of audio-recorded individual sessions will be reviewed and an Auditor Checklist completed by individuals trained in behavioral activation. The Auditor Checklist covers treatment objectives from both health education and behavior therapy for that session. Perfect treatment fidelity (and zero contamination) for a health education session will be evidenced by 100% of health education objectives and 0% of behavior therapy objectives met. When a session is reviewed with less than 85% of treatment-specific objectives met and/or any evidence of contamination (>0% other condition objectives met), the auditor will inform the PI who will remediate interventionist training as needed. This process will continue through all treatment waves so that counselor/educator drift can be swiftly corrected.
Treatment Fidelity of Group Weight Loss Sessions
Provider and auditor checklists were created for the group weight loss visits to ensure that treatment objectives for each group session are met in each condition. Contamination will be evident in group sessions if elements of behavioral activation are being met during group sessions. Group leaders will not be trained in or have expertise with behavioral activation or any other therapeutic approaches for depression. However, participants with depression may spontaneously bring depression into the group discussion. Group leaders will emphasize that the purpose of the groups is to help participants improve their lifestyle habits, which can have a positive effect on stress and depression. Group leaders will be trained to stay within the protocol and not engage in problem-solving around depression-specific issues. They also will notify the PI if a participant requests further help, to determine whether a referral is deemed necessary. As for individual visits, an audited session with less than 85% of treatment-specific objectives met and/or any evidence of contamination will be brought to the attention of the PI who will remediate interventionist training as needed.