Adaptive Responses to Overfeeding and Weight (ARrOW)

April 6, 2023 updated by: University of Colorado, Denver

Adaptive Responses to Overfeeding and Weight Regain in Reduced Obese Individuals

To more effectively address the problem of weight regain following weight loss for obese individuals, this study will evaluate the underlying biology of the reduced obese state. In depth studies of appetite, energy expenditure, physical activity levels and fat metabolism will be completed in obese and reduced obese individuals; with the latter subdivided into those who have lost weight with diet alone or diet plus exercise. Individuals will be studied following a brief overfeeding period to better understand how differences in biological responses to overeating might be involved in promoting or protecting against weight gain.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The persistent problem of weight regain following weight loss is perhaps the most significant barrier to addressing the current obesity epidemic. The biological drive to regain weight following weight loss is due in part to increased appetite leading to increased energy intake (EI) and reductions in energy expenditure (EE) in part due to changes in energy expended in physical activity (PA). These physiological adaptations to weight loss are most relevant during episodes of dietary indiscretion resulting in overfeeding (OF) when reduced obese (RO) people fail to respond to the state of positive energy balance in a way that maintains the reduced state. There is increasing evidence that RO individuals who exercise (RO-Ex) are less like to regain as compared to RO individuals who are sedentary (RO-Sed). Previous studies were conducted on the effects of OF on EI, EE, PA and fat metabolism in non-obese individuals either prone (OP) or resistant to obesity (OR). Subjects were then followed for 5 years to measure weight change. These studies showed that differences in the response of nocturnal fat oxidation and higher levels of moderate/vigorous PA following OF correlated with 5 year weight gain suggesting that these factors were potentially important mechanisms for weight gain. Previous work has shown that measures of hunger fail to suppress with OF in RO individuals and that nocturnal fat oxidation is reduced in RO-Sed but maintained in RO-Ex following a day that included a bout of exercise. This study will look at the responses of EE, EI, PA and fat metabolism to OF (40% above basal energy for 3 days) in obese, RO-Sed and RO-Ex men and women and correlate these responses to weight change over the subsequent year. The hypothesis is that changes in the response of one or more of these variables to OF will correlate with weight regain. The Significance of the studies lies in the fact that subjects will begin to clarify the metabolic mechanisms that underlie a propensity for weight regain in RO individuals. Innovation: The proposed studies will systematically examine a range of responses to OF and prospectively correlate them with weight gain while taking into account aspects of behavior relevant to weight regain. The hope is that these studies will lay a foundation for future studies that will examine the mechanisms underlying specific adaptive responses that directly relate to weight regain and help with the design of strategies to address and/or respond to these processes.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University Of Colorado Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria.

  • BMI of 30-38 kg/m2 and weight stable over the previous 6 months.
  • Satisfied with current weight and not planning to lose weight at the time of enrollment (persons with obesity control group) -or- not satisfied with current weight and motivated to lose weight at the time of enrollment (reduced obese groups)
  • No more than 90 min or 3 bouts of planned physical activity/wk.
  • Pass a medical and physical screening performed by the study physician.
  • Reporting a habitual, regular sleep-wake cycle for the month preceding screening that involved going to bed between 2200 and 0100 h and getting up between 0600 and 0900 h with >7 h and <9.25 h in bed.
  • Live or work within 45 minutes of the CU-AMC (reduced obese groups only) (exceptions may be made at the discretion of the Study PI on a case by case basis for highly motivated subjects).
  • Own a smartphone (Android or Apple iOS).
  • For Females
  • Not currently pregnant or lactating
  • Not pregnant within the past 6 months
  • Not planning to become pregnant in the next 12 months; sexually active women of childbearing potential may be enrolled if they use a reliable means of contraception
  • Capable and willing to provide informed consent, understand exclusion criteria, and accept the randomized group assignment (reduced obese groups)

Exclusion criteria.

  • Being considered unsafe to participate as determined by the study physician;
  • Taking medications affecting weight, triglycerides, or energy intake/energy expenditure in the last 3 months;
  • Having abnormal blood chemistry and/or hematology as deemed significant by the study physician;
  • Ever having a history of systemic, psychiatric, neurological disease, or drug and alcohol abuse;
  • History of cardiovascular disease, diabetes, uncontrolled hypertension, untreated thyroid, renal, hepatic diseases, dyslipidemia or any other medical condition affecting weight or lipid metabolism;
  • Score > 18 on Beck Depression Index (BDI) will require further assessment by the study physician to determine if it is appropriate for the subject to participate in the study;
  • Use of a continuous positive airway pressure (CPAP) device for the treatment of obstructive sleep apnea (OSA). A score of >10 on the Epworth sleepiness scale or >5 on the Pittsburgh Sleep Quality Index will require further assessment by the study physician to determine if it is appropriate for the subject to participate in the study;
  • Being positive for human immunodeficiency virus or hepatitis B or C;
  • History of surgical procedure for weight loss at any time (e.g. gastroplasty, gastric bypass, gastrectomy or partial gastrectomy, adjustable banding, gastric sleeve);
  • Being a smoker or having been a smoker in the previous 6 months;
  • Abnormal eating patterns identified by registered dietitian interview (dietary fat<15%, dietary fat>45%, dietary protein >30%);
  • Working night shifts;
  • Night eating syndrome (at least 25% of food intake is consumed after the evening meal and/or at least two episodes of nocturnal eating per week);
  • Traveling > 2 time zones 2 weeks prior to an inpatient CTRC study visit;
  • Currently participating in any formal weight loss or physical activity programs or clinical trials.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Control
Persons with obesity who do not undergo weight loss will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes.
Other: Overfeeding
3-day hypercaloric diet designed to overfeed by 40% above total daily energy requirements
Experimental: Reduced obese + diet + exercise
Persons with obesity randomized to a weight loss program consisting of caloric restriction, behavioral support, and supervised endurance exercise training. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes.
Other: Overfeeding
3-day hypercaloric diet designed to overfeed by 40% above total daily energy requirements
Other: Weight Loss
12-wk weight loss intervention using a meal replacement strategy (Health & Nutrition Technology, Carmel, CA), with an 8-10% weight loss goal
Other: Exercise training
16-wk supervised endurance exercise training program
Active Comparator: Reduced obese + diet group
Persons with obesity randomized to a weight loss program consisting of caloric restriction and behavioral support. Following weight loss persons in this group will participate in an inpatient assessment to measure metabolic responses to a 3 day eucaloric diet or a 3 day overfeeding challenge. Participants will be followed for 1 year after the metabolic studies to track longitudinal changes in body weight and other relevant health outcomes.
Other: Overfeeding
3-day hypercaloric diet designed to overfeed by 40% above total daily energy requirements
Other: Weight Loss
12-wk weight loss intervention using a meal replacement strategy (Health & Nutrition Technology, Carmel, CA), with an 8-10% weight loss goal

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fat oxidation as a correlate of weight regain as measured by room calorimetry
Time Frame: 24 hour period on day 7 of two diet conditions - one overfed & one eucaloric condition; weeks 16 & 20
Fat oxidation as a correlate of weight regain will be assessed in both reduced obese groups with room calorimetry on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
24 hour period on day 7 of two diet conditions - one overfed & one eucaloric condition; weeks 16 & 20

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Body weight per scale
Time Frame: Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Body weight will be measured via clinic scale. Change in body weight in response to the weight loss intervention
Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Body Composition via DXA
Time Frame: Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Body composition will be measured via DXA, Change in body composition in response to the weight loss intervention
Baseline, after 12 week weight loss intervention and 1 year after the end of second study condition
Change in substrate utilization as measured by room calorimetry
Time Frame: 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and week 16 & 20 for reduced groups
Substrate utilization will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and week 16 & 20 for reduced groups
Change in nocturnal lipolysis as measured by use of stable isotope tracer
Time Frame: 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Lipolysis will be measured using stable isotope tracers (change = overfeeding diet condition - eucaloric diet condition)
24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Change in total energy expenditure (TEE) as measured by room calorimetry
Time Frame: 24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
TEE will be measured by room calorimetry (change = overfeeding diet condition - eucaloric diet condition)
24 hour period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Change in spontaneous physical activity (SPA) as measured by accelerometers
Time Frame: 7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
SPA will be measured using accelerometers (change = overfeeding diet condition - eucaloric diet condition)
7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Change in spontaneous food intake measured with an ad libitum diet
Time Frame: 3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Spontaneous food intake will be measured during a 3 day ad libitum diet (change = overfeeding diet condition - eucaloric diet condition)
3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Change in hunger and satiety using Visual Analog Scale
Time Frame: 3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Hunger and satiety will be measured using visual analog scales (change = overfeeding diet condition - eucaloric diet condition)
3 days - on days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Change in 24h hormone and metabolite profiles as measured by assay of plasma samples
Time Frame: 3 days - days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
24h hormone and metabolite profiles will be assayed in plasma samples obtained during inpatient study visits (change = overfeeding diet condition - eucaloric diet condition)
3 days - days 8-10 - of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Lipolysis as a correlate of weight regain as measured by stable isotope tracer
Time Frame: 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Lipolysis as a correlate of weight regain will be assessed in both reduced obese groups with a stable isotope tracer on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Total energy expenditure (TEE) as a correlate of weight regain as measured by room calorimetry
Time Frame: 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
TEE as a correlate of weight regain will be assessed in both reduced obese groups with room calorimetry on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Spontaneous physical activity (SPA) as a correlate of weight regain as measured by accelerometers
Time Frame: 7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
SPA as a correlate of weight regain will be assessed in both reduced obese groups with accelerometers on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
7 days, on days 4-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Spontaneous food intake as a correlate of weight regain as measured with an ad libitum diet
Time Frame: 3 days - days 8-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
SPA as a correlate of weight regain will be assessed in both reduced obese groups with an ad libitum diet on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
3 days - days 8-10 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
24h hormone and metabolite profiles as a correlate of weight regain as measured by assay of plasma samples
Time Frame: 24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
24h hormone and metabolite profiles as a correlate of weight regain will be assessed in both reduced obese groups by assay of plasma samples on two occasions, once after 3 days of overfeeding and once after 3 days of an energy balanced diet.
24 period, on day 7 of two diet conditions - eucaloric and overfed; week 1 and 4 for controls and weeks 16 and 20 for reduced
Total daily energy expenditure as a correlate of weight regain as measured by doubly labeled water
Time Frame: two 1 week periods at 1 month and 1 year after second diet condition; week 8 and week 56 for controls and week 24 and week 72 for reduced
Total daily energy expenditure as a correlate of weight regain will be measured in both reduced obese groups using doubly labeled water after the second diet condition intervention
two 1 week periods at 1 month and 1 year after second diet condition; week 8 and week 56 for controls and week 24 and week 72 for reduced
Correlates of Weight Regain as measured by questionnaire
Time Frame: 30 minutes at baseline and every 8 weeks for 1 year following second diet condition; weeks 12, 20, 28, 36, 44, 52 for controls and weeks 28, 36, 44, 52, 60, 68, for reduced.
Correlates of weight regain will be assessed in both reduced obese groups with questionnaires periodically over the intervention and follow-up period
30 minutes at baseline and every 8 weeks for 1 year following second diet condition; weeks 12, 20, 28, 36, 44, 52 for controls and weeks 28, 36, 44, 52, 60, 68, for reduced.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in fitness as measured by indirect calorimetry
Time Frame: 30 minutes at baseline and 1 year following second diet condition; Reduced group will have an additional measurement at week 12 following weight loss period.
Fitness will be measured using indirect calorimetry during a graded exercise test to volitional exhaustion
30 minutes at baseline and 1 year following second diet condition; Reduced group will have an additional measurement at week 12 following weight loss period.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Colorado, Denver

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Colorado, Boulder

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 15, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 7, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18-0091

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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