Research Aimed at Improving Both Mood and Weight

Study Overview
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Brief Summary
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The RAINBOW study is an NIH R01-funded randomized controlled trial to evaluate the clinical and cost effectiveness and implementation potential of a primary care integrated multicondition intervention program to help improve mood and weight for obese adults with clinically significant depressive symptoms. The ENGAGE study is a mechanistic investigation added to the main trial with funding through the NIH common fund for the Science of Behavior Change roadmap initiative. Beginning Jan 11, 2016, at least 100 of newly enrolled trial participants will be consented to undergo additional assays evaluating neurobiological mechanisms of self-regulation.

Detailed Description
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The large numbers of primary care patients affected by coexisting obesity and depression and common risk factors for diabetes and heart disease underscore the urgency of developing effective, accessible, and sustainable interventions that use an integrated, multicondition care management approach. The RAINBOW trial will rigorously evaluate the clinical and cost effectiveness and potential for real-world implementation of an innovative intervention that integrates a behavioral weight loss program and a collaborative stepped care program for depression, incorporates conventional clinic- and home-based modes of care delivery (e.g., office visits plus phone consults and take-home DVD), and leverages low-cost, wide-reach health information technologies (e.g., Web, secure email, and mobile texting). Beginning Jan 11, 2016, at least 100 of newly enrolled trial participants will also be consented to undergo additional assays evaluating neurobiological mechanisms of self-regulation, including emotional regulation, cognitive control and self-reflection. Given its focus on transforming primary care management of obesity and depression and common cardiometabolic risk factors to evidence-based, patient-centered care, as well as the likely scalability of the proposed intervention, the study has high potential for significant clinical and public health impact. Furthermore, elucidating the neurobiological mechanisms of self-regulation will significantly advance precision lifestyle medicine by enabling mechanism-targeted individualization of treatment.

Official Title
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RCT on Co-management of Obesity, Depression, and Elevated CVD Risk in Primary Care-- Engaging Self-regulation Targets to Understand the Mechanisms of Behavior Change and Improve Mood and Weight Outcomes

Conditions
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Depression, Obesity

Intervention / Treatment
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* Behavioral: RAINBOW Intervention Program


Participation Criteria
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Eligibility Criteria
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RAINBOW Inclusion criteria: Ethnicity and race: Any; Obesity: BMI≥30 kg/m2 for non-Asians; BMI≥27 kg/m2 for Asians; Clinically significant depressive symptoms: PHQ-9≥10; A PAMF patient for ≥1 year Seen in primary care at least once in the preceding 24 months; Able and willing to enroll and meet the requirements of the study Exclusion criteria: Inability to speak, read or understand English; Having no reliable telephone service, no device to use to watch a DVD, or no regular Internet access via a computer and/or mobile device; Had bariatric surgery within the past 12 months or plans to undergo bariatric surgery during the 24-month study period; Ongoing psychiatric care outside of the PAMF network. Active suicidal ideation that includes active plan and/or intent; Any Axis I disorder other than Minor or Major Depressive Disorder and/or Dysthymia, with the exception of any comorbid Anxiety Disorder; Active Bulimia Nervosa within the past 12 months (however Binge Eating Disorder without purging is not an exclusionary condition); Active alcohol or substance use disorder (including prescription drugs). Pre-existing diabetes (other than during pregnancy) or diabetes diagnosed as a result of fasting blood glucose or hemoglobin A1c levels obtained through study screening; Pre-existing cardiovascular disease. Diagnosis of cancer (other than non-melanoma skin cancer) that is/was active or treated with radiation or chemotherapy within the past 12 months; Severe medical comorbidities that require aggressive treatment, e.g., stage 4 or greater renal disease, liver failure; Diagnosis of a terminal illness and/or in hospice care; Residence in long-term care facility; Cognitive impairment based on the Callahan 6-item scale Plan to move out of the area or transfer care outside PAMF during the study period; Investigator discretion for reasons of clinical safety or protocol adherence. ENGAGE Inclusion criteria: • RAINBOW participant Exclusion criteria: Weight over 350 pounds MRI is contraindicated Traumatic brain injury

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAINBOW Intervention Program<br>An integrated intervention program for helping to improve mood and weight in adults who may be at risk for diabetes and heart disease. | Behavioral: RAINBOW Intervention Program<br>* Integrated lifestyle intervention with as-needed antidepressant pharmacotherapy to treat coexisting obesity and depression in adults in primary care<br>|
| No Intervention: Usual Care<br>Usual Care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-Primary Outcome: Body Mass Index (BMI) | Integrated intervention treatment response | 12 months | 
| Co-Primary Outcome: Depression Symptom Checklist 20 (SCL-20) Score | Depression Symptom Checklist 20 (SCL-20) questionnaire score. SCL-20, average scores of the 20 items with a range from 0 (not at all) to 4 (extremely). SCL-20 cutoff points scores of ≤0.75, >0.75-1.5, >1.5- 2.0, and >2.0 represent remission, mild depression, moderate depression, and severe depression, respectively. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index | Derived from height and weight measurements | 24 months | 
| Depression Symptom Checklist 20 (SCL-20) Score | SCL-20 full questionnaire. SCL-20, average scores of the 20 items with a range from 0 (not at all) to 4 (extremely). SCL-20 cutoff points scores of ≤0.75, >0.75-1.5, >1.5- 2.0, and >2.0 represent remission, mild depression, moderate depression, and severe depression, respectively. | 24 months | 
| Weight | Weight measurements | 12 months | 
| Weight | Weight measurements | 24 months | 
| Depression Remission (Number of Participants With SCL-20 Scores <0.5) | Depression remission defined by Depression Symptom Checklist 20 (SCL-20) scores <0.5 | 12 months | 
| Depression Remission (Number of Participants With SCL-20 Score <0.5) | Depression remission defined by Depression Symptom Checklist 20 (SCL-20) scores <0.5 | 24 months | 
| Depression Treatment Response (Number of Participants With ≥50% Decrease in SCL-20 Scores From Baseline) | Depression treatment response defined by 50% decline in SCL-20 symptom scores | 12 months | 
| Depression Treatment Response (Number of Participants With ≥50% Decrease in SCL-20 Scores From Baseline) | Depression treatment response defined by 50% decline in SCL-20 symptom scores | 24 months | 
| Clinically Significant Weight Loss (Number of Participants With ≥5% Weight Loss From Baseline) | 5% or greater weight loss from baseline | 12 months | 
| Clinically Significant Weight Loss (Number of Participants With ≥5% Weight Loss From Baseline) | 5% or greater weight loss from baseline | 24 months | 
| Cost-effectiveness | Average annual per person spending on medical care services (2018 real US dollars) | 12 months | 
| Obesity-related Psychosocial Functioning (Obesity-related Problem Scale) | Obesity-related Problem Scale, average scores of 8 questions with a range from 0 (no at all) to 3 (extremely). The average score is then multiplied by 100 and divided by 3 to convert to a scale of 0-100, with a higher score indicating more obesity-related problems. | 12 months | 
| Anxiety (GAD-7) | Self-administered questionnaire. Total scores of the 7 items with a range from 0 (no symptoms) to 21 (most severe symptoms). | 12 months | 
| Generic Health-related Quality of Life (SF-8 - Physical Component (PCS) ) | Self-administered questionnaire - Generic Health-related Quality of Life (SF-8 - physical component (PCS) ) Physical and mental composite scores, a population scale ranged from 0 (lowest quality of life) to 100 (highest quality of life) summed by the total converted scores of each value of the 8 questions. These summary scales have been normalized in the U.S. population (value=50). The higher score indicates better self-reported health-related quality of life. | 12 months | 
| Generic Health-related Quality of Life (SF-8 - Mental Component (MCS) ) | Self-administered questionnaire - Generic Health-related Quality of Life (SF-8 - Mental Component (MCS) ). Physical and mental composite scores, a population scale ranged from 0 (lowest quality of life) to 100 (highest quality of life) summed by the total converted scores of each value of the 8 questions. These summary scales have been normalized in the U.S. population (value=50). The higher score indicates better self-reported health-related quality of life. | 12 months | 
| Disability (Sheehan Disability Scale) | Self-administered Sheehan Disability Scale questionnaire. Sheehan Disability Scale, total scores of the 3 items with a range from 0 (unimpaired) to 30 (highly impaired). Scores of ≥5 on any of the 3 scales (Work/school [0-10], Social life [0-10], and Family life/home responsibilities [0-10]) are associated with signiﬁcant functional impairment. | 12 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Activity) | Self-administered questionnaire: Utility-based Health-related Quality of Life - USUAL ACTIVITIES (e.g. work, study, housework, family or leisure activities). A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 12 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Pain) | Self-administered questionnaire: Utility-based Health-related Quality of Life - PAIN/DISCOMFORT. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 12 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Anxiety/Depression) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Anxiety and depression. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 12 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Mobility) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Mobility. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 12 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Self-care) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Self-care. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 12 months | 
| Sleep Disturbance T-score | Sleep disturbance T-score, a population scale with a range from 25 (extreme disturbance or impairment) to 80 (not at all) converted from the raw total score of 8-item questionnaire. A score of 50 represents the average of the calibration sample, which was generally more enriched for chronic illness. | 12 months | 
| Sleep Impairment T-score | Sleep Impairment T-score, a population scale with a range from 25 (extreme disturbance or impairment) to 80 (not at all) converted from the raw total score of 8-item questionnaire. A score of 50 represents the average of the calibration sample, which was generally more enriched for chronic illness. | 12 months | 
| Regulation of Cognition | Regulation of cognition is measured using lab-based fMRI. To measure regulation of cognition, fMRI assays include activation and connectivity values for approximately 300 brain regions, various physiological measures (heart rate, skin conductance, respiration rate) recorded on participant while performing tasks in fMRI scanner, performance and reaction times on various cognitive control web-based tasks, and online questionnaires administered with REDCap (COPE Inventory for Cognitive Coping and Clutter Image Rating Scale). Data analysis is ongoing because it involves complex imaging fMRI data processing and analyzing. | Baseline, 2, 6, 12, and 24 months | 
| Regulation of Self-reflection | Regulation of cognition is measured using lab-based fMRI. To measure regulation of self-reflection, fMRI assays include activation and connectivity values for approximately 300 brain regions, various physiological measures (heart rate, skin conductance, respiration rate) recorded on participant while performing tasks in fMRI scanner, and online questionnaires administered with REDCap (BRISC Questionnaire of Emotional Resilience and Self-efficacy). Data analysis is ongoing because it involves complex imaging fMRI data processing and analyzing. | Baseline, 2, 6, 12, and 24 months | 
| Regulation of Emotion | Regulation of emotion is measured using lab-based fMRI. To measure regulation of emotion, fMRI assays include activation and connectivity values for approximately 300 brain regions, various physiological measures (heart rate, skin conductance, respiration rate) recorded on participant while performing tasks in fMRI scanner, performance and reaction times on various emotional web-based tasks, and online questionnaires administered with REDCap (emotional regulation questionnaire, early life stress questionnaire, and emotional regulation ratings success and strategies). Data analysis is ongoing because it involves complex imaging fMRI data processing and analyzing. | Baseline, 2, 6, 12, and 24 months | 
| Obesity-related Psychosocial Functioning (Obesity-related Problem Scale) | Obesity-related Problem Scale, average scores of 8 questions with a range from 0 (no at all) to 3 (extremely). The average score is then multiplied by 100 and divided by 3 to convert to a scale of 0-100, with a higher score indicating more obesity-related problems. | 24 months | 
| Anxiety (GAD-7) | Self-administered questionnaire. Total scores of the 7 items with a range from 0 (no symptoms) to 21 (most severe symptoms). | 24 months | 
| Generic Health-related Quality of Life (SF-8 - Physical Component (PCS) ) | Self-administered questionnaire - Generic Health-related Quality of Life (SF-8 - physical component (PCS) ). Physical and mental composite scores, a population scale ranged from 0 (lowest quality of life) to 100 (highest quality of life) summed by the total converted scores of each value of the 8 questions. These summary scales have been normalized in the U.S. population (value=50). The higher score indicates better self-reported health-related quality of life. | 24 months | 
| Generic Health-related Quality of Life (SF-8 - Mental Component (MCS) ) | Self-administered questionnaire - Generic Health-related Quality of Life (SF-8 - Mental Component (MCS) ). Physical and mental composite scores, a population scale ranged from 0 (lowest quality of life) to 100 (highest quality of life) summed by the total converted scores of each value of the 8 questions. These summary scales have been normalized in the U.S. population (value=50). The higher score indicates better self-reported health-related quality of life. | 24 months | 
| Disability (Sheehan Disability Scale) | Self-administered Sheehan Disability Scale questionnaire. Sheehan Disability Scale, total scores of the 3 items with a range from 0 (unimpaired) to 30 (highly impaired). Scores of ≥5 on any of the 3 scales (Work/school [0-10], Social life [0-10], and Family life/home responsibilities [0-10]) are associated with signiﬁcant functional impairment. | 24 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Activity) | Self-administered questionnaire: Utility-based Health-related Quality of Life - USUAL ACTIVITIES (e.g. work, study, housework, family or leisure activities). A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 24 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Pain) | Self-administered questionnaire: Utility-based Health-related Quality of Life - PAIN/DISCOMFORT. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 24 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Anxiety/Depression) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Anxiety and depression. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 24 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Mobility) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Mobility. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 24 months | 
| Utility-based Health-related Quality of Life (EQ-5D-Self-care) | Self-administered questionnaire: Utility-based Health-related Quality of Life - Self-care. A 5-point scale (1) No problems, (2) Slight problems, (3) Moderate problems, (4) Severe problems, and (5) Extreme problems. | 24 months | 
| Sleep Disturbance T-score | Sleep disturbance T-score, a population scale with a range from 25 (extreme disturbance or impairment) to 80 (not at all) converted from the raw total score of 8-item questionnaire. A score of 50 represents the average of the calibration sample, which was generally more enriched for chronic illness. | 24 months | 
| Sleep Impairment T-score | Sleep Impairment T-score, a population scale with a range from 25 (extreme disturbance or impairment) to 80 (not at all) converted from the raw total score of 8-item questionnaire. A score of 50 represents the average of the calibration sample, which was generally more enriched for chronic illness. | 24 months | 
| Leisure Time Physical Activity | Physical activity was assessed as metabolic equivalent task (MET) minutes per week of leisure-time physical activity of at least moderate intensity based on the sum of the weighted physical activity minutes for moderate (weight: 4 METs), hard (weight: 6 METs), and very hard (weight: 10 METs) activities from the 7-day Physical Activity Recall. | 7-day Physical Activity Recall was administered at 12 months | 
| Total Energy Expenditure | Totally energy expenditure was measured using the 7-day Physical Activity Recall and provides estimates of total daily energy expenditures (total energy expenditure = sleep hours × 1 MET + light activity hours × 1.5 METs + moderate activity hours × 4 METs + hard activity hours × 6 METs + very hard activity hours × 10 METs). | 7-day Physical Activity Recall was administered at 12 months | 
| Total Calorie Intake | Total calorie intake was measured using 24-hour dietary recalls and provides total energy intake. | One day's 24-hour dietary recall was administered at 12 months | 
| DASH (Dietary Approach to Stop Hypertension) Score | Using 24-hour diet recalls, DASH scores were calculated based on combining nine nutrient targets (i.e. total fat, saturated fat, protein, cholesterol, fiber, magnesium, calcium, sodium and potassium). The intermediate target of each nutrient was half-way between the DASH target and population mean (based on the National Health and Nutrition Examination Surveys 2007-2008, latest data available at the inception of the study). For a nutrient, participants reaching the DASH target were assigned one point, those reaching the intermediate target were assigned a half-point, and those not meeting the intermediate target were given 0 points. The DASH score was the sum of points for all nine nutrients and ranged from 0 to 9. DASH score is a measure of diet quality, with higher score indicating higher diet quality | One day's 24-hour dietary recall was administered at 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depressive symptoms, Integrated therapy, Cardiometabolic risk, Self-regulation, Behavior change, Precision medicine, Lifestyle, BMI