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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04499950

Acronym

A-NEW

Enrollment

Registered

2020-08-05

Start date

2021-02-08

Completion date

2024-01-10

Last updated

2025-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer, Overweight or Obesity

Brief summary

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.

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.

Interventions

DRUGContrave

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.

BEHAVIORALBehavioral 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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

OTHER

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients With 5 Percent Weight Loss (in SLOW-BWL)	6 months	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.

Secondary

Measure	Time frame	Description
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	Baseline, 2 months and 6 Months	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.
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	Baseline, 2 months and 6 Months	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.
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	Baseline, 2 months and 6 Months	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.
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	Baseline, 2 months and 6 Months	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.
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	Baseline, 2 months and 6 Months	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).
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	Baseline, 2 months and 6 Months	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.
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	Baseline, 2 months and 6 Months	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.

Other

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. 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. 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.	38
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 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.	15
Total	53

Baseline characteristics

Characteristic	SLOW-BWL	FAST-BWL	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	6 Participants	5 Participants	11 Participants
Age, Categorical Between 18 and 65 years	32 Participants	10 Participants	42 Participants
Age, Continuous	56.5 years	61 years	59 years
Breast Cancer Stage Stage 0 (Ductal carcinoma in situ (DCIS))	2 Participants	3 Participants	5 Participants
Breast Cancer Stage Stage 1	23 Participants	6 Participants	29 Participants
Breast Cancer Stage Stage 2	8 Participants	2 Participants	10 Participants
Breast Cancer Stage Stage 3	5 Participants	4 Participants	9 Participants
Race/Ethnicity, Customized Black or African American	12 Participants	1 Participants	13 Participants
Race/Ethnicity, Customized Other	2 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized White/ Caucasian	24 Participants	13 Participants	37 Participants
Region of Enrollment United States	38 Participants	15 Participants	53 Participants
Sex: Female, Male Female	38 Participants	15 Participants	53 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 38	0 / 15
other Total, other adverse events	28 / 38	4 / 15
serious Total, serious adverse events	0 / 38	0 / 15

Outcome results

Primary

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.

Time frame: 6 months

Population: Only 32 participants in the SLOW-BWL arm completed intervention per protocol

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
SLOW-BWL	Number of Patients With 5 Percent Weight Loss (in SLOW-BWL)	16 Participants

Secondary

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.