Research Aimed at Improving Both Mood and Weight (RAINBOW-ENGAGE)

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

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.

Study Overview

• Status: Completed
• Conditions: Depression; Obesity
• Intervention / Treatment: Behavioral: RAINBOW Intervention Program

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 409
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAINBOW Intervention Program; 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; Integrated lifestyle intervention with as-needed antidepressant pharmacotherapy to treat coexisting obesity and depression in adults in primary care
No Intervention: Usual Care; Usual Care.

What is the study measuring?

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
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
Change in Activation of Left Amygdala From Baseline Functional Magnetic Resonance Scan at 2 Months (Regulation of Emotion)	Regulation of emotion, specially activation of the amygdala for nonconscious threat-related emotional reactivity, is assessed using fMRI. In the facial emotion viewing paradigm, facial expression stimuli are standardized black and white photographs of 8 identities (4 female, 4 male) with evoked expressions of threat-related emotions (fear, anger), sad-related emotions (sadness) and reward-related emotions (happiness), along with neutral. To assess amygdala activation for the negative affect circuit, our analysis focused on threatening faces only. Threat stimuli included a combination of fear and anger stimuli relative to neutral blocks. A hemodynamic response convolved boxcar function was used to model the BOLD response for each block of emotional expressions to threat and to sadness relative to neutral face blocks. General linear models were then specified for each task to investigate the contrasts of interest. Higher beta-weight indicates higher activation of the amygdala.	Baseline, 2 months
Change in Activation of Right Amygdala From Baseline Functional Magnetic Resonance Scan at 2 Months (Regulation of Emotion)	Regulation of emotion, specially activation of the amygdala for nonconscious threat-related emotional reactivity, is assessed using fMRI. In the facial emotion viewing paradigm, facial expression stimuli are standardized black and white photographs of 8 identities (4 female, 4 male) with evoked expressions of threat-related emotions (fear, anger), sad-related emotions (sadness) and reward-related emotions (happiness), along with neutral. To assess amygdala activation for the negative affect circuit, our analysis focused on threatening faces only. Threat stimuli included a combination of fear and anger stimuli relative to neutral blocks. A hemodynamic response convolved boxcar function was used to model the BOLD response for each block of emotional expressions to threat and to sadness relative to neutral face blocks. General linear models were then specified for each task to investigate the contrasts of interest. Higher beta-weight indicates higher activation of the amygdala.	Baseline, 2 months

Collaborators and Investigators

• Sponsor: Palo Alto Medical Foundation
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Pittsburgh; University of Illinois at Chicago; University of Washington; Stanford University; Sutter Health
• Investigators: Principal Investigator: Jun Ma, MD, PhD, University of Illinois at Chicago; Principal Investigator: Leanne Williams, PhD, Stanford University

Publications and helpful links

General Publications

• Kannampallil T, Dai R, Lv N, Xiao L, Lu C, Ajilore OA, Snowden MB, Venditti EM, Williams LM, Kringle EA, Ma J. Cross-trial prediction of depression remission using problem-solving therapy: A machine learning approach. J Affect Disord. 2022 Jul 1;308:89-97. doi: 10.1016/j.jad.2022.04.015. Epub 2022 Apr 7.
• Lv N, Lefferts WK, Xiao L, Goldstein-Piekarski AN, Wielgosz J, Lavori PW, Simmons JM, Smyth JM, Stetz P, Venditti EM, Lewis MA, Rosas LG, Snowden MB, Ajilore OA, Suppes T, Williams LM, Ma J. Problem-solving therapy-induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial. Am J Clin Nutr. 2021 Dec 1;114(6):2060-2073. doi: 10.1093/ajcn/nqab280.
• Goldstein-Piekarski AN, Wielgosz J, Xiao L, Stetz P, Correa CG, Chang SE, Lv N, Rosas LG, Lavori PW, Snowden MB, Venditti EM, Simmons JM, Smyth JM, Suppes T, Lewis MA, Ajilore O, Ma J, Williams LM. Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial. EBioMedicine. 2021 May;67:103387. doi: 10.1016/j.ebiom.2021.103387. Epub 2021 May 17.
• Lv N, Xiao L, Rosas LG, Venditti EM, Smyth JM, Lewis MA, Snowden MB, Ronneberg CR, Williams LM, Gerber BS, Ajilore OA, Patel AS, Ma J. Sex Moderates Treatment Effects of Integrated Collaborative Care for Comorbid Obesity and Depression: The RAINBOW RCT. Ann Behav Med. 2021 Nov 18;55(12):1157-1167. doi: 10.1093/abm/kaaa125.
• Goldhaber-Fiebert JD, Prince L, Xiao L, Lv N, Rosas LG, Venditti EM, Lewis MA, Snowden MB, Ma J. First-Year Economic and Quality of Life Effects of the RAINBOW Intervention to Treat Comorbid Obesity and Depression. Obesity (Silver Spring). 2020 Jun;28(6):1031-1039. doi: 10.1002/oby.22805. Epub 2020 Apr 22.
• Lv N, Xiao L, Majd M, Lavori PW, Smyth JM, Rosas LG, Venditti EM, Snowden MB, Lewis MA, Ward E, Lesser L, Williams LM, Azar KMJ, Ma J. Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial. PLoS One. 2020 Apr 21;15(4):e0231743. doi: 10.1371/journal.pone.0231743. eCollection 2020. Erratum In: PLoS One. 2020 Aug 21;15(8):e0238276.
• Rosas LG, Azar KMJ, Lv N, Xiao L, Goldhaber-Fiebert JD, Snowden MB, Venditti EM, Lewis MM, Goldstein-Piekarski AN, Ma J. Effect of an Intervention for Obesity and Depression on Patient-Centered Outcomes: An RCT. Am J Prev Med. 2020 Apr;58(4):496-505. doi: 10.1016/j.amepre.2019.11.005. Epub 2020 Feb 14.
• Ma J, Rosas LG, Lv N, Xiao L, Snowden MB, Venditti EM, Lewis MA, Goldhaber-Fiebert JD, Lavori PW. Effect of Integrated Behavioral Weight Loss Treatment and Problem-Solving Therapy on Body Mass Index and Depressive Symptoms Among Patients With Obesity and Depression: The RAINBOW Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):869-879. doi: 10.1001/jama.2019.0557.
• Ma J, Xiao L, Lv N, Rosas LG, Lewis MA, Goldhaber-Fiebert JD, Venditti EM, Snowden MB, Lesser L, Ward E. Profiles of sociodemographic, behavioral, clinical and psychosocial characteristics among primary care patients with comorbid obesity and depression. Prev Med Rep. 2017 Aug 5;8:42-50. doi: 10.1016/j.pmedr.2017.07.010. eCollection 2017 Dec.
• Ma J, Yank V, Lv N, Goldhaber-Fiebert JD, Lewis MA, Kramer MK, Snowden MB, Rosas LG, Xiao L, Blonstein AC. Research aimed at improving both mood and weight (RAINBOW) in primary care: A type 1 hybrid design randomized controlled trial. Contemp Clin Trials. 2015 Jul;43:260-78. doi: 10.1016/j.cct.2015.06.010. Epub 2015 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2014
• Primary Completion (Actual): January 17, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimated): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Precision medicine; BMI; Lifestyle; Behavior change; Depressive symptoms; Cardiometabolic risk; Self-regulation; Integrated therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Depression; Obesity
• Other Study ID Numbers: 14-05-323; R01HL119453 (U.S. NIH Grant/Contract); UH2HL132368 (U.S. NIH Grant/Contract)