Diabetes Mellitus, Type 2
Conditions
Keywords
type 2 diabetes, whole fruit, diabetes remission, glycemic control, liver fat, intrahepatic lipid, controlled feeding trial
Brief summary
Diabetes costs the U.S. healthcare system more than any other disease, and nearly half of Americans will develop either diabetes or prediabetes in their lifetime. It is therefore critical to find new strategies to treat or reverse diabetes. One such approach is adopting a healthy diet, which can dramatically improve blood sugar levels in adults with type 2 diabetes and even induce diabetes remission. Despite this, not much is known about which food groups are most effective at improving blood sugar levels in patients with diabetes. Interestingly, of the various food groups, epidemiologic data suggests that whole fruit may be one of the most efficacious at both preventing type 2 diabetes and improving blood sugar in patients with type 2 diabetes. However, few clinical trials have investigated the effects of whole fruit on blood sugar control. This study will therefore be the first to determine the effects of increasing whole fruit as a food group in type 2 diabetes patients. This supervised controlled feeding trial will test whether consuming a diet rich in whole fruit for 12 weeks can improve glycemic control and cardiometabolic health in weight-stable adults with type 2 diabetes. The primary endpoint is glycemic control. Since changes in medication doses can skew the interpretation of glycemic outcomes, glycemic control will be assessed hierarchically (in descending order of importance) using (a) attainment of nondiabetic glycemia without medications (as a proxy for diabetes remission), (b) medication effect scores, (c) mean glucose during an oral glucose tolerance test, and (d) 24-hour mean glucose from continuous glucose monitoring. As secondary aims, this study will also test whether consuming a large amount of fructose in whole food form affects liver fat, pancreatic fat, and cardiovascular disease risk factors.
Interventions
BEHAVIORALHigh-Fruit Diet
In this supervised controlled feeding study, participants will consume a diet rich in whole fruit. During the Ramp-Up Phase (Weeks 1-4), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In the Main Phase (Weeks 5-12), participants will consume a whole fruit-rich, eucaloric diet that provides 50% of calories in the form of whole fruit. The non-fruit portion of the diet will be styled as a Mediterranean Diet. Participants will be required to approximately keep their weight stable throughout the intervention.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Lab values and week 0, 4, and 12 endpoints are assessed blinded by individuals not affiliated with the protocol. Also, data cleaning will be performed while being blinded to the timepoint.
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 20-70 years old * BMI ≤45.0 kg/m\^2 * First diagnosed with type 2 diabetes within the past 6 years * HbA1c between 6.0-9.5%%
Exclusion criteria
* On insulin * Diagnosis of diabetes before age 18 * Estimated glomerular filtration rate \< 45 ml/min per 1.732 m\^2 * Heart attack in the past 6 months or severe or unstable heart failure * On weight loss medication * Change in the dosage of a chronic medication that may affect study endpoints within the past 3 months * Clinically significant laboratory abnormality (e.g. abnormal hemoglobin levels) * Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones * Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise safety or data validity * Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years * Lost or gained more than 5 kg of weight in the past 6 months * Pregnant, planning to become pregnant in the next 12 months, or breastfeeding * Major psychiatric condition that would affect the ability to participate in the study * Not able to eat the provided study meals * Behavioral factors or circumstances that may impede adhering to the dietary intervention * Not able to do the MRI/MRS abdominal scan, such as due to claustrophobia, implanted metal objects, or a body girth of 60 cm or greater
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diabetes Remission Rate | Change from baseline to week 12 | Percentage of patients who can maintain non-diabetic levels 24-hour mean glucose without the aid of pharmacotherapy at week 12 |
| Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | mg/dl |
| Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT) | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | mg/dl |
| Medication Effect Score (MES) | Change from baseline to Week 12 | % (or percentage). This quantity estimates the percentage by which all anithyperglycemic medications taken by a patient would lower HbA1c levels (i.e., percent of glycated hemoglobin molecules). Higher values indicate a higher dose and/or potency of medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dynamic Beta-Cell Responsivity | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | Phi\_dynamic during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_dynamic is a measure of beta-cell responsiveness during first-phase insulin secretion. It is a dimensionless index (arbitrary units), where higher values denote greater insulin secretion. |
| Insulin Sensitivity | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model. |
| Static Beta-Cell Responsivity | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | Phi\_static during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_static is a measure of beta-cell responsiveness during second-phase insulin secretion. The units of measure are min\^-1, and higher values denote greater insulin secretion. |
| Mean Insulin During a 3-hour OGTT | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | mU/l |
| Mean C-peptide During a 3-hour OGTT | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported. | ng/ml |
| Mean Amplitude of Glycemic Excursions From CGM | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | mg/dl |
| Fasting Glucose | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | mg/dl |
| HbA1c | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | percentage |
| Liver Fat (Intrahepatic Lipid) | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI) |
| Pancreatic Fat | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Percentage as measured using MRS and 3-point M-Dixon MRI methods |
| Systolic and Diastolic Blood Pressure | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | mm Hg |
| Heart Rate | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | beats per minute |
| Time-in-range Metrics From CGM | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Time during which glucose levels are between 70 and 300 mg/dl |
| Lipids | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Fasting total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gut Microbiome Diversity | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Diversity metrics (i.e., alpha and beta diversity) |
| Subcutaneous Abdominal Fat | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Subcutaneous abdominal fat as measured using MRI (kg) |
| Visceral Fat | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Visceral fat as measured using MRI (kg) |
| Gut Microbiome Composition | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Taxonomic composition and abundances |
| Preference and Sensitivity to Sweet Tastes | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured on a 0-100 mm visual analog scale (VAS), using a Sweetness Taste Test |
| Diet Satisfaction | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured on a 0-100 mm visual analog scale (VAS) |
| Habitual Fruit Consumption | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | As estimated using a series of semi-quantitative food frequency questions from the Diet History Questionnaire |
| Food Cravings | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured on five-point scales by the Food Craving Inventory-II |
| Fruit Liking Visual Analog Scales | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured by VAS on a 0-100 mm scale |
| Food Attitudes and Behaviors | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured by a modified version of the National Cancer Institute (NCI) 2007 Food Attitudes and Behaviors Survey, which covers constructs including attitudes and beliefs, fruit and vegetable consumption, eating behaviors, and food preferences |
| General Health Status | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | Healthy days (along various dimensions) as measured by the Centers for Disease Control and Prevention's (CDC) Health-Related Qualify of Life questionnaire |
| Depression | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured on a 0-27 point scale by the Patient Health Questionnaire-9 |
| Mood States | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | As measured on a 5-point scale by the Profile of Mood States Short-Form |
| Intervention Satisfaction and Feedback | Week 12 | As measured by qualitative exit interview |
| Waist Circumference | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints) | cm |
| Body Weight | Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints); assessed weekly | kg |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Fruit Diet Whole fruit-rich diet (\
50% of calories from whole fruit)
High-Fruit Diet: Participants will consume a diet rich in whole fruit. During Phase I (Weeks 1-4; supervised controlled feeding), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In Phase II (Week 5-12; supervised controlled feeding), participants will consume a whole fruit-rich, eucaloric diet that provides 50% of calories in the form of whole fruit. The non-fruit portion of the diet will be styled as a Mediterranean Diet. Participants will be required to approximately keep their weight stable during Phases I and II. In the Follow-Up Phase (Months 4-12; free-living), participants will be instructed to continue consuming at least one-third of their diet as whole fruit and to make healthy food choices. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | High-Fruit Diet |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 34 |
| other Total, other adverse events | 18 / 34 |
| serious Total, serious adverse events | 0 / 34 |
Outcome results
Primary
Diabetes Remission Rate
Percentage of patients who can maintain non-diabetic levels 24-hour mean glucose without the aid of pharmacotherapy at week 12
Time frame: Change from baseline to week 12
Population: Results were analyzed per-protocol in completers who met the specified weight stability criterion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fruit-Rich Diet | Diabetes Remission Rate | % Who Maintained Non-Diabetic Glycemia Without Pharmacotherapy | 3 Participants |
| Fruit-Rich Diet | Diabetes Remission Rate | % Who Weaned Off All Antihyperglycemic Medications | 6 Participants |
p-value: <0.0001Binomial Test
Primary
Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES
mg/dl
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: Results were analyzed per-protocol in completers who met the specified weight stability criterion
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES | Main Analysis | -12 mg/dl | Standard Error 7 |
| Fruit-Rich Diet | Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES | Post Hoc Analysis Excluding 1 Outlier with Very Low C-peptide Levels | -18 mg/dl | Standard Error 6 |
Primary
Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT)
mg/dl
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT) | All n=10 participants, including those who changed their medication doses | 11 mg/dl | Standard Error 9 |
| Fruit-Rich Diet | Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT) | n=4 participants without medication changes | -20 mg/dl | Standard Error 12 |
Primary
Medication Effect Score (MES)
% (or percentage). This quantity estimates the percentage by which all anithyperglycemic medications taken by a patient would lower HbA1c levels (i.e., percent of glycated hemoglobin molecules). Higher values indicate a higher dose and/or potency of medications.
Time frame: Change from baseline to Week 12
Population: Results were analyzed per-protocol in completers who met the specified weight stability criterion
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fruit-Rich Diet | Medication Effect Score (MES) | -0.5 % (see definition under Description) | Standard Error 0.5 |
Secondary
Dynamic Beta-Cell Responsivity
Phi\_dynamic during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_dynamic is a measure of beta-cell responsiveness during first-phase insulin secretion. It is a dimensionless index (arbitrary units), where higher values denote greater insulin secretion.
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Dynamic Beta-Cell Responsivity | All n=10 participants, including those who changed their medication doses | 135 arbitrary units * 10^9 | Standard Error 60 |
| Fruit-Rich Diet | Dynamic Beta-Cell Responsivity | n=4 participants without medication changes | 122 arbitrary units * 10^9 | Standard Error 133 |
Secondary
Fasting Glucose
mg/dl
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
HbA1c
percentage
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Heart Rate
beats per minute
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Insulin Sensitivity
Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model.
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Insulin Sensitivity | All n=10 participants, including those who changed their medication doses | 1.27 dl/kg/min/μU/ml | Standard Error 0.99 |
| Fruit-Rich Diet | Insulin Sensitivity | n=4 participants without medication changes | 3.03 dl/kg/min/μU/ml | Standard Error 1.61 |
Secondary
Lipids
Fasting total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Liver Fat (Intrahepatic Lipid)
Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Mean Amplitude of Glycemic Excursions From CGM
mg/dl
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Mean C-peptide During a 3-hour OGTT
ng/ml
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Mean C-peptide During a 3-hour OGTT | n=4 participants without medication changes | -1.7 ng/ml | Standard Error 0.5 |
| Fruit-Rich Diet | Mean C-peptide During a 3-hour OGTT | All n=10 participants, including those who changed their medication doses | -0.4 ng/ml | Standard Error 0.4 |
Secondary
Mean Insulin During a 3-hour OGTT
mU/l
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Mean Insulin During a 3-hour OGTT | All n=10 participants, including those who changed their medication doses | -17.1 mU/l | Standard Error 4.7 |
| Fruit-Rich Diet | Mean Insulin During a 3-hour OGTT | n=4 participants without medication changes | -38.1 mU/l | Standard Error 6.7 |
Secondary
Pancreatic Fat
Percentage as measured using MRS and 3-point M-Dixon MRI methods
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Static Beta-Cell Responsivity
Phi\_static during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_static is a measure of beta-cell responsiveness during second-phase insulin secretion. The units of measure are min\^-1, and higher values denote greater insulin secretion.
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Population: We present the results both in all participants (n=10) and those who were on stable doses of medications (n=4). The former data is presented for completeness only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fruit-Rich Diet | Static Beta-Cell Responsivity | All n=10 participants, including those who changed their medication doses | -3.0 10^9/min | Standard Error 4 |
| Fruit-Rich Diet | Static Beta-Cell Responsivity | n=4 participants without medication changes | 0.9 10^9/min | Standard Error 10.6 |
Secondary
Systolic and Diastolic Blood Pressure
mm Hg
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Secondary
Time-in-range Metrics From CGM
Time during which glucose levels are between 70 and 300 mg/dl
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Body Weight
kg
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints); assessed weekly
Other Pre-specified
Depression
As measured on a 0-27 point scale by the Patient Health Questionnaire-9
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Diet Satisfaction
As measured on a 0-100 mm visual analog scale (VAS)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Food Attitudes and Behaviors
As measured by a modified version of the National Cancer Institute (NCI) 2007 Food Attitudes and Behaviors Survey, which covers constructs including attitudes and beliefs, fruit and vegetable consumption, eating behaviors, and food preferences
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Food Cravings
As measured on five-point scales by the Food Craving Inventory-II
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Fruit Liking Visual Analog Scales
As measured by VAS on a 0-100 mm scale
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
General Health Status
Healthy days (along various dimensions) as measured by the Centers for Disease Control and Prevention's (CDC) Health-Related Qualify of Life questionnaire
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Gut Microbiome Composition
Taxonomic composition and abundances
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Gut Microbiome Diversity
Diversity metrics (i.e., alpha and beta diversity)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Habitual Fruit Consumption
As estimated using a series of semi-quantitative food frequency questions from the Diet History Questionnaire
Time frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Other Pre-specified
Intervention Satisfaction and Feedback
As measured by qualitative exit interview
Time frame: Week 12
Other Pre-specified
Mood States
As measured on a 5-point scale by the Profile of Mood States Short-Form
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Preference and Sensitivity to Sweet Tastes
As measured on a 0-100 mm visual analog scale (VAS), using a Sweetness Taste Test
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Subcutaneous Abdominal Fat
Subcutaneous abdominal fat as measured using MRI (kg)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Visceral Fat
Visceral fat as measured using MRI (kg)
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Other Pre-specified
Waist Circumference
cm
Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)