Adaptive Nutrition and Exercise Weight Loss (A-NEW) Study (A-NEW)

A Phase II Single Arm Adaptive Weight Loss Study in Women With Early Stage Breast Cancer

This is a single arm phase II study designed to determine the effects of pharmacotherapy and a remote behavioral weight loss intervention on weight loss in breast cancer survivors who are overweight or obese, and the impact of successful weight loss on serum biomarkers and gut microbiome.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Overweight or Obesity
• Intervention / Treatment: Drug: Contrave; Behavioral: Behavioral Weight Loss

Detailed Description

The investigators will evaluate the extent to which implementation of a chronic weight loss medication, Contrave® (Naltrexone/Bupropion), is associated with achieving ≥5% weight loss. All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose ≥5%, designated fast responders, will continue with BWL alone (FAST-BWL) while those who lose <5%, designated slow responders, will continue BWL and initiate Contrave (SLOW-BWL). The SLOW-BWL arm will receive at least 16 weeks of Contrave (as per Federal Drug Administration [FDA] recommended administration) starting at week 9 and discontinue if ≥5% weight loss is not achieved at month 6. During month 3, all participants continue to have weekly calls with the behavioral coach and will be asked about symptoms, which may be related to initiation of pharmacotherapy; any symptoms are reported to the PI for further evaluation. In addition to total weight loss, the investigators will evaluate biomarkers associated with obesity, microbiome and cardiometabolic factors.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female, at least 3 months after completion of local therapy (e.g. surgery, radiation), and if applicable, adjuvant chemotherapy
• Diagnosed within 10 years with histologically-confirmed ductal carcinoma in situ (DCIS) or stage I-III invasive carcinoma of the breast
• Up to date with recommended screening mammography within one year
• Current BMI ≥ 30 kg/m2 or BMI 27.0-29.9 kg/m2 with hypertension, non-insulin dependent diabetes or hyperlipidemia; and weight ≤ 400 lbs
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Willingness to change diet, physical activity, track behaviors, engage in weekly and monthly contacts and visit, and take chronic weight loss medication
• Able to read and write the English language without assistance and daily access to the e-mail and/or smartphone
• Patient is aware of her diagnosis, understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form.

Exclusion Criteria:

• Serious/uncontrolled medical condition at the discretion of the Protocol Chair/designee likely to hinder accurate measurement of weight or any condition for which weight loss is contraindicated or would affect adipokine and inflammatory markers (e.g. active malignancy, end stage renal disease on dialysis, cirrhosis, autoimmune disease, adrenal disease, uncontrolled hypertension, seizure disorder, and history of bariatric surgery)
• Pregnant or nursing within past 6 months, or plans to become pregnant in the next year
• Currently enrolled or planning to enroll in a weight loss program (e.g. Weight Watchers, Jenny Craig, Nutrisystem and Medifast) or to take a chronic weight loss medication.
• Diabetes on insulin or sulfonylureas within the past 3 months
• Unstable psychiatric disorder or bulimia/anorexia nervosa
• Alcohol, nicotine or substance abuse; or undergoing abrupt discontinuation of alcohol, benzodiazepine, barbiturate or anti-epileptic drug

• Use of the following medications are excluded:

  • Monoamine oxidase (MAO) inhibitors (must be >14 days from discontinuation)
  • Thyroid medication use unless on stable doses for at least the past 3 months
  • Buproprion containing products or opiate agonists (must be >14 days from discontinuation)
  • Medications that cause weight loss (e.g., lorcaserin, phentermine, orlistat, Qsymia, Contrave) within the past 3 months
  • Medications that are likely to cause weight gain or prevent weight loss (e.g., corticosteroids, lithium, olanzapine, risperidone, clozapine, oral contraceptive pills, hormone replacement therapy) within the past 3 months. NOTE: An exception to this is that SSRI's and SNRI's are allowed if participant has been on stable doses for at least 3 months (if discontinued, a washout of 2 weeks from prior selective serotonin reuptake inhibitor (SSRI)/Serotonin-norepinephrine reuptake inhibitor (SNRI) use is required).
  • Medications that may affect adipokine or inflammatory markers (e.g., metformin, glitazones, steroids, angiotensin converting enzyme (ACE) inhibitors, beta blockers and statins) unless on stable doses ≥3 months prior to registration (if discontinued, a washout of 2 weeks from prior use is required). Concurrent NSAIDs are allowed if use is limited to <3 times per week; chronic NSAIDs are permitted on study only if use has been ≥3 times per week for at least 3 months prior to registration and is expected to continue.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLOW-BWL; All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose <5%, designated slow responders, will continue BWL and initiate Contrave (SLOW-BWL). The SLOW-BWL arm will receive at least 16 weeks of Contrave [as per the Food and Drug Administration (FDA) recommended administration] starting at week 9 and discontinue if ≥5% weight loss is not achieved at month 6.	Drug: Contrave; Initiate Contrave at 1 tab in morning (AM) for Week 9; then 1 tab in AM and 1 tab in evening (PM) for Week 10; then 2 tab in AM and 1 tab in PM for Week 11; then 2 tab in AM and 2 tab in PM for week 12; then constant dose for months 4-6.; Other Names: Naltrexone/Bupropion; Behavioral: Behavioral Weight Loss; 6 months of behavioral weight loss. First 3 months are weekly calls with coach and then transition to monthly calls for months 4-6.
Active Comparator: FAST-BWL; All patients will receive the POWER-remote behavioral weight loss intervention (BWL) and have a behavioral coach for the duration of the 6 month study. During months 1-3, the behavioral coach will call weekly. From months 4-6, the behavioral coach will call monthly. At week 9, those who lose ≥5%, designated fast responders, will continue with BWL alone (FAST-BWL)	Behavioral: Behavioral Weight Loss; 6 months of behavioral weight loss. First 3 months are weekly calls with coach and then transition to monthly calls for months 4-6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With 5 Percent Weight Loss (in SLOW-BWL)	To assess the rate of SLOW-BWL patients attaining at least 5% weight loss of their baseline body weight at 6 months with the addition of Contrave to BWL at week 9.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Scores on Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function - Short Form Questionnaire Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function. The total score ranges from 33.5 to 61.7. The higher the score, the better the physical function.	Baseline, 2 months and 6 Months
Change in Scores on Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference - Short Form Questionnaire Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference. The total score ranges from 41.0-67.4. The lower the score, the better the pain interference.	Baseline, 2 months and 6 Months
Change in Scores on Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - Short Form Questionnaire Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue. The total score ranges from 39.6 to 62.0. The lower the score, the less the fatigue.	Baseline, 2 months and 6 Months
Change in Scores on Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Depression - Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Patient-Reported Outcomes Measurement Information System (PROMIS) Depression. The total score ranges from 37.1-71.4. The lower the score, the less depression.	Baseline, 2 months and 6 Months
Change in Scores on Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Anxiety - Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety. Scores range 36.3-71.5, with higher scores representing more severe anxiety symptoms.	Baseline, 2 months and 6 Months
Change in Scores on the Medical Outcomes Study (MOS) Sexual Functioning Scale Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Medical Outcomes Study (MOS) Sexual Function. Score range 0-100 with higher score indicating less functioning. Four items are rated on a 5-point scale (1=not a problem, 2=little of a problem, 3=somewhat of a problem, 4=very much of a problem, and 5=not applicable).	Baseline, 2 months and 6 Months
Change in Scores on Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) Among FAST-BWL vs SLOW-BWL, as Well as Participants Who Achieve ≥5% Weight Loss at 6 Months vs Those Who Are Unable to	To report the change in scores at 2 and 6 months to baseline among FAST-BWL vs SLOW-BWL arms for Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES). Scores ranging from 39.0 to 73.0. Higher scores indicate greater impact from symptoms.	Baseline, 2 months and 6 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With 5% Weight Loss (in FAST-BWL)	To assess the proportion of women in the FAST-BWL arm who maintain ≥5% weight loss at 6 months.	6 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Breast Cancer Research Foundation; American Institute for Cancer Research; Hopkins-WellSpan Cancer Research Fund
• Investigators: Principal Investigator: Jennifer Sheng, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): January 10, 2024
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Neoplasms by Site; Neoplasms; Overnutrition; Body Weight; Body Weight Changes; Skin Diseases; Breast Diseases; Overweight; Weight Loss; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Alcohol Deterrents; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Anti-Obesity Agents; Narcotic Antagonists; Bupropion hydrochloride, naltrexone hydrochoride drug combination; Naltrexone; Bupropion
• Other Study ID Numbers: IRB00223131

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes