Nutrition for Precision Health, Powered by the All of Us
NCT ID: NCT05701657
Last Updated: 2025-12-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
NA
8000 participants
INTERVENTIONAL
2023-04-14
2027-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The Module 2 DSMT response curves are the primary outcomes (dependent variables) for AI/ML algorithms that predict individual responses to diet patterns.
As a secondary objective, NPH will evaluate the validity and acceptability of technology-based dietary assessment tools. The Automated Self-Administered 24-hour recall (ASA24), Automatic Ingestion Monitor-2 (AIM-2), and the mobile food record (mFR) will be evaluated in Modules 2 and 3, and the ASA24 food record and the image-assisted ASA24 recall will be evaluated only in Module 3. Total energy intake, macronutrient and dietary fiber intake data are the main outcomes for validity testing compared against measures of actual intake. Acceptability will be determined from feedback surveys.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Module 1: Phenotyping (non-interventional)
Module 2: Community-dwelling controlled feeding group (Intervention arm 1)
Module 3: Residential (Live-in) controlled feeding group (Intervention arm 2)
Approximately 8,000 participants are anticipated to be enrolled in Module 1. From this cohort, approximately 1,200 participants will enroll in Module 2, and a separate subset of Module 1 participants (approximately 150 participants) will enroll in Module 3. Module 1 is observational and only Modules 2 and 3 are interventional in nature (intervention arms).
Module 1 is a phenotyping observational study. Participants undergo comprehensive characterization across an 8 to 10-day baseline period for assessments including: clinical measures, biospecimen collection, wearable sensor monitoring, questionnaires, and a liquid meal test (LMT). During the LMT, participants ingest a standardized liquid meal with a dose of acetaminophen for estimating gastric emptying and provide timed blood samples for postprandial profiling. The LMT is a diagnostic stimulus used solely for feature generation and is not being evaluated as an intervention. The resulting Module 1 high dimensional dataset supports machine learning methods (e.g., PCA, clustering, recursive feature elimination) for candidate predictor discovery and is therefore not listed in the Arms/Interventions section. Module 1 data will be used to develop novel statistical and machine learning methods to learn individual and generalizable causal models of nutrition and health, particularly in the presence of missing or incomplete data. The scale of Module 1 enables discovery of causal pathways and moderators between physical and contextual measures, LMT responses, and continuous glucose monitoring (CGM) data. These insights are critical for developing models that not only predict individual dietary responses but also explain why and under what conditions they occur.
Module 2 is a community dwelling controlled feeding arm (Intervention arm 1). A subset of Module 1 participants will enroll in Module 2, in which participants consume three standardized eucaloric diets; Diet A, Diet B, Diet C, in a crossover sequence. Each diet period lasts 12-14 days, separated by a minimum of 14-day washout period between diets. All meals are provided, but participants remain in their community dwelling environments. Participants undergo one of six possible sequences of dietary interventions, reflecting all possible orderings of the three diets (ABC, ACB, BCA, BAC, CAB, and CBA). To reduce potential bias, all six diet sequences are included in the crossover design. Rather than assigning diet sequences to individual participants, a cohort-based randomization approach is used to reduce operational burden on the metabolic kitchens. In this approach, pre-generated schedules involving all 6 diet sequences are randomly assigned to the clinical site metabolic kitchens, with each diet sequence corresponding to a cohort. Participants are then enrolled into the cohorts. The six diet orders are repeated over time at each site until the full enrollment targets for Modules 2 and 3 are met. Each site follows a different randomized version of the overall cohort schedule, which ensures distribution of the possible diet orders across time and clinical sites while preserving balance and logistical feasibility. Wearable-generated data (like accelerometry and CGM), physical and contextual measures are collected throughout.
At the completion of each diet participants are provided a standardized breakfast meal test, DSMT, from each of the three provided diets (Diet A, B, C). The 0-4 hour postprandial response curves are then used to evaluate inter-individual variation and unmask features collected in Module 1 and 2 that contribute to the AI/ML predictions of the response.
Each breakfast serves as a controlled stimulus to reveal underlying biological features from rich multimodal data streams, including clinical, molecular, behavioral, environmental, and social domains that may drive interindividual variability in metabolic response. For each DSMT, participants provide blood samples for up to nine time points over four hours. Analyte concentrations of glucose, insulin, triglycerides, and GLP-1, are used to construct response curves. The primary outcomes are the area under the curve (AUC) for each analyte (glucose, insulin, triglycerides, GLP-1) following each DSMT. This approach parallels a cardiac stress test: the stimulus (the meal) is a probe to expose individual variability in physiological function. Module 2 data will also be used to develop novel statistical and machine learning methods that produce individual and generalizable causal models of nutrition and health.
Module 3 is a controlled feeding study (Intervention arm 2) that is implemented in the live-in/residential setting. A separate subset of Module 1 participants completes the same three diets (Diet A, B, C) as in Module 2, but while residing in a research setting with full supervision of intake, activity, and sleep. The same cohort randomization scheme as in Module 2 determines diet order. The residential environment in Module 3 provides the highest degree of experimental control, allowing isolation of physiological effects of diet composition. Participants undergo a diet-specific meal test (DSMT) as well as a liquid meal test (LMT) accompanied by a dose of acetaminophen after completing each of the diets. In addition, intake balance studies are conducted in this module using the doubly labeled water assessments and DXA for body composition. Data from Module 3 will help quantify and separate variance in the AI/ML models attributable to adherence and other community dwelling factors observed in Module 2 and enables rigorous and controlled comparison against causal relationships discovered in Module 2 data.
In both Modules 2 and 3, participants are masked to the nutritional profile of each diet to minimize expectancy bias. Investigators and diet implementation staff are unmasked.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
CROSSOVER
OTHER
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Community-Dwelling Controlled-Feeding Arm (Module 2)
Participants drawn from Module 1 will receive three standardized diets (A, B, and C) in one of six sequences. Diet sequences are assigned at the cohort level based on a pre-defined site-specific schedule. All meals are provided while participants remain living in their own homes. Each diet period lasts \~14 days, separated by washouts of at least 14 days. Participants are masked to the nutritional content of each diet. Data collection includes wearable device outputs, physical and contextual assessments, and biospecimens. This arm evaluates metabolic responses to controlled diets under real-world, community-dwelling conditions.
Diet A
This diet has high amounts of fruits/vegetables, whole grains, and beans, moderate amounts of dairy, meat/poultry/eggs, nuts/seeds, and olive oil, and very low amounts of sugar sweetened drinks and desserts.
Diet B
This diet has high amounts of refined grains, meat/poultry/egg, sugar sweetened drinks, snacks, desserts, and processed foods. It has a moderate amount of dairy and low amounts of fruits/vegetables, whole grains, and fish.
Diet C
This diet has moderate-high amounts of vegetables, meat/poultry/egg, nuts/seeds, dairy and fats/oils, low amounts of fruits, and very low amounts of grains and sugars.
Residential Controlled-Feeding Arm (Module 3)
A separate group of participants drawn from Module 1, who are not enrolled in Module 2, will receive the same three standardized diets administered in Module 2 while residing in a fully supervised residential setting. Diet sequences are assigned at the cohort level based on a pre-defined site-specific schedule. Each diet period will last approximately 14 days and will be separated by washout periods of at least 14 days. Intake, activity, and sleep will be closely monitored. Participants will also complete the same liquid meal test administered in Module 1 (see detailed description) after each of the diet periods. A wealth of measurements will be collected, including data from wearables, physical and contextual measures, and biospecimens. Intake balance studies are conducted in this module using the doubly labeled water assessments and DXA for body composition. Module 3 is designed to isolate the response to different diets from behavioral variability observed in community settings.
Diet A
This diet has high amounts of fruits/vegetables, whole grains, and beans, moderate amounts of dairy, meat/poultry/eggs, nuts/seeds, and olive oil, and very low amounts of sugar sweetened drinks and desserts.
Diet B
This diet has high amounts of refined grains, meat/poultry/egg, sugar sweetened drinks, snacks, desserts, and processed foods. It has a moderate amount of dairy and low amounts of fruits/vegetables, whole grains, and fish.
Diet C
This diet has moderate-high amounts of vegetables, meat/poultry/egg, nuts/seeds, dairy and fats/oils, low amounts of fruits, and very low amounts of grains and sugars.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Diet A
This diet has high amounts of fruits/vegetables, whole grains, and beans, moderate amounts of dairy, meat/poultry/eggs, nuts/seeds, and olive oil, and very low amounts of sugar sweetened drinks and desserts.
Diet B
This diet has high amounts of refined grains, meat/poultry/egg, sugar sweetened drinks, snacks, desserts, and processed foods. It has a moderate amount of dairy and low amounts of fruits/vegetables, whole grains, and fish.
Diet C
This diet has moderate-high amounts of vegetables, meat/poultry/egg, nuts/seeds, dairy and fats/oils, low amounts of fruits, and very low amounts of grains and sugars.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Module 1 -- Must be willing and able to comply with Module 1 protocol; Must provide informed consent for Module 1.
* Module 2 -- Must have completed Module 1; Must provide informed consent for Module 2; Must agree to comply with protocol over a period of approximately 10 to 12 weeks and up to six months. This includes consuming only the foods provided during periods of controlled feeding. Module 2 has three controlled feeding periods each lasting approximately two weeks with at least two weeks between feeding periods, and up to 6 months allowed for completion of the Module.
* Module 3 -- Must have completed Module 1; Must provide informed consent for Module 3; Must agree to comply with protocol over a period of approximately 10 to 12 weeks and up to 6 months. This includes being domiciled three times, for two weeks each, and consuming only the foods provided during the domiciled periods. There is at least two weeks between domiciled periods, and up to 6 months allowed for completion of the Module.
Exclusion Criteria
1. Any change to the participant's status from the time of All of Us enrollment that would render them ineligible for All of Us (e.g., being incarcerated, no longer living in the United States, or withdrawn from that study).
2. Inability to provide informed consent and engage in informed consent procedures
3. Participants who suffer from allergic reactions to, or are unwilling to consume, any components of the liquid mixed meal (e.g., milk products, soy products)
4. Barriers to safe insertion of peripheral IV canula:
1. Contraindications to peripheral IV canula insertion such as local skin infection, inflammation, trauma or burns if all the upper extremities were involved and there is no unaffected extremity available for IV placement; or
2. A need for long-term IV access (e.g., ESRD); or
3. Lymphedema or deep vein thrombosis (DVT) in the extremity of the IV (in the case where another extremity is not available); or
4. Coagulopathy requiring blood thinning products; or
5. Arteriovenous (AV) graft or fistula in the extremity of the IV (in the case where another extremity is not available)
5. Pregnancy-related conditions:
1. Gestational age precluding completion of the Module by 36 weeks. A pregnant participant should complete visit 1 by gestational age 34 weeks, 0 days and complete Module 1 by week 36.
2. Severe morning sickness limiting mixed meal tolerance test (MMTT) consumption
6. Certain types of disease states:
1. Dumping syndrome or inability to consume the volume of the MMTT liquid
2. Severe malabsorption such as history of short gut syndrome or need for parenteral or enteral nutrition
3. Less than 12-months post-metabolic or bariatric surgery
4. History of chronic pancreatitis (e.g., Cystic fibrosis) complicated by inability to tolerate the volume of the MMTT liquid
5. Health conditions requiring chronic blood transfusions or iron infusions
6. Hemoglobin \<9.5 g/dL at screening
7. Serious illness and in hospice or palliative care for terminal disease
8. Swallowing issues:
1. Self-reported difficulty tolerating solids or liquids
2. Aspiration risks that require change in thickness of liquid or dietary modifications
9. Short term antibiotic use. For example, active antibiotics use for an ongoing acute infection
10. Blood donation in the last 3 months
11. GLP-1 agonist medication (e.g. Semaglutide) instability as defined by less than 3 months of continuous use
* Module 2
1. Any change to the participant's status from the time of All of Us enrollment that would render them ineligible for All of Us (e.g., being incarcerated, no longer living in the United States, or withdrawn from that study)
3. Inability to provide informed consent and engage in informed consent procedures
4. Inability or failure to complete all critical elements from Module 1 (dietary, physical activity and sleep assessments, continuous glucose monitoring, MMTT)
5. Participants who are already enrolled in Module 3
6. Participants who are unlikely to be able to adhere to the protocol, based on structured adherence assessment by a study registered dietitian or other trained staff. This includes participants who have known allergic reactions to, or unwillingness to consume, study foods in Module 2 (e.g., gluten, meat, fish, nuts, dairy products) that cannot be reasonably accommodated by the metabolic kitchen within allowable criteria for the test diets.
7. Participants who plan to relocate to an area not served by NPH or travel plans that do not permit completion of the Module over a period of up to 6 months.
8. Pregnancy-related conditions:
1. Gestational age precluding completion of the Module by week 36. A pregnant participant must be able to begin the first diet by gestational age 26 weeks, 0 days and complete the Module by week 36.
2. High risk pregnancy defined as fetal anomaly, gestational hypertension (SBP \>140 mmHg and DBP \>90 mmHg), pre-eclampsia, or gestational diabetes mellitus
9. Possible ethanol (alcohol) use disorder defined by Alcohol Use Disorders Identification Test (AUDIT) score of \>15
10. History of surgery for the treatment of obesity and:
1. Self-reported dumping syndrome; or
2. Following a special diet prescribed by their practitioner
11. Uncontrolled disease states:
1. Hypertension \>160/100mmHg
2. Exacerbation of underlying gastrointestinal disease, including inflammatory bowel disease or other malabsorptive disorders
3. Decompensated cirrhosis
4. Previously diagnosed diabetes Mellitus with HbA1c \>12% at screening
5. Newly diagnosed diabetes within the past three months, or HbA1c \>6.5% at screening in a person not previously diagnosed with diabetes.
12. Participants with a history of end-stage renal disease (ESRD) on hemodialysis
13. Active infectious diseases (e.g., active tuberculosis \< 3 months from symptom onset or positive test, COVID \< 1 month from symptom onset or positive test)
14. Malignancy (e.g., cancer) actively receiving cytotoxic chemotherapy (oral or infusions) treatment except for nonmelanoma skin cancers during the study period
15. Participants who require dietary restrictions due to a medical condition or are on a prescribed diet for underlying chronic diseases
16. Participants with type 1 or type 2 diabetes on insulin
17. Participants aged ≥ 75 years with type 2 diabetes taking prescribed medications that can cause hypoglycemia (e.g. sulfonylureas, glinides), or on a prescribed diet
18. Hospitalization for a chronic disease (e.g., congestive heart failure, stroke) within the past three months
19. Requiring transfusions/apheresis during study period
20. Participants with a current diagnosis of, or who have received treatment for, bulimia or anorexia nervosa within the past 3 years
21. Participants with major psychiatric disorders, including major depression, schizophrenia, or psychosis, who have been hospitalized in the past six (6) months or are currently enrolled in treatment programs
22. Hemoglobin \<9.5 g/dL at screening
23. Myocardial infarction, invasive cardiac procedure, participation in a cardiac or acute rehabilitation programs, transient ischemic attacks, or unstable arrhythmias within the past 3 months
* Module 3
2. Participants who are already enrolled in Module 2
4. Inability to abstain from tobacco or nicotine use, vaping, alcohol, illicit drug use, or recreational drug use for two (2) consecutive weeks while domiciled in the clinical unit. Nicotine gum, pouch, or patch are permitted.
5. Any condition requiring in-person treatments or visits during the study period. This will not be accommodated by the domiciling protocol; however, tele-health visits with the participants regular doctor are permitted.
6. Lactation or other infant care needs that cannot be accommodated while domiciled in the clinical unit
7. Depression as assessed by:
1. Patient Health Questionnaire (PHQ-9) score ≥ 15; or
2. Affirmative answer to PHQ-9 suicidality question: "Thoughts that you would be better off dead or of hurting yourself in some way"
8. Unable to engage in daily self-care activities (e.g., bathing, transferring, toileting, feeding, dressing)
9. Uncontrolled endocrine disorders (such as Cushing's disease, pituitary disorders, diabetes)
10. Uncontrolled pain requiring frequent or daily treatment, or adjustment of medication requiring weekly or bi-weekly visits. Pain medications used on an as-needed basis (PRN), such as acetaminophen or NSAIDs, are not excluded.
11. Chronic prescription medications that would pose logistical and safety issues for participation
18 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institutes of Health (NIH)
NIH
University of North Carolina, Chapel Hill
OTHER
Northwestern University
OTHER
Illinois Institute of Technology
OTHER
University of Chicago
OTHER
Pennington Biomedical Research Center
OTHER
Louisiana State University Health Sciences Center in New Orleans
OTHER
University of California, Davis
OTHER
University of California, Los Angeles
OTHER
Cedars-Sinai Medical Center
OTHER
University of Alabama at Birmingham
OTHER
Tufts University
OTHER
Massachusetts General Hospital
OTHER
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
National Center for Advancing Translational Sciences (NCATS)
NIH
National Cancer Institute (NCI)
NIH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
City University of New York, School of Public Health
OTHER
Mayo Clinic
OTHER
University of California, San Diego
OTHER
University of Hawaii
OTHER
Vanderbilt University Medical Center
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
National Center for Complementary and Integrative Health (NCCIH)
NIH
National Institute of Drug Abuse
FED
Public Health Informatics Computational and Operations Research
UNKNOWN
University of Southern California
OTHER
Cornell University
OTHER
University of Alabama, Tuscaloosa
OTHER
North Carolina State University
OTHER
University of North Carolina, Charlotte
OTHER
Duke University
OTHER
Stevens Institute of Technology
OTHER
Purdue University
OTHER
United States Military Academy West Point
FED
USDA, Western Human Nutrition Research Center
FED
North Carolina Central University
OTHER
Wake Forest University Health Sciences
OTHER
Boston University
OTHER
Children's Hospital of Richmond
UNKNOWN
Virginia Commonwealth University
OTHER
Verily Life Sciences LLC
INDUSTRY
Indiana University
OTHER
Fred Hutchinson Cancer Center
OTHER
Columbia University
OTHER
University of Pennsylvania
OTHER
RTI International
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Marie G Gantz, PhD
Role: PRINCIPAL_INVESTIGATOR
RTI International
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Alabama at Birmingham
Birmingham, Alabama, United States
USDA Western Human Nutrition Research Center
Davis, California, United States
University of California, Los Angeles
Los Angeles, California, United States
University of California, Davis
Sacramento, California, United States
Cedars Sinai Medical Center
West Hollywood, California, United States
Northwestern University
Chicago, Illinois, United States
Illinois Institute of Technology
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States
Louisiana State University Health Sciences Center
New Orleans, Louisiana, United States
Tufts University
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of North Carolina at Chapel Hill - Chapel Hill Clinic
Chapel Hill, North Carolina, United States
University of North Carolina at Chapel Hill - Kannapolis
Kannapolis, North Carolina, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Sarah Ehrlicher, PhD, RDN
Role: primary
Skye Stewart, MC, CCRP
Role: primary
Jeraldine Guzman
Role: primary
Skye Stewart, MS, CCRP
Role: primary
Christina Lombardi, PhD
Role: primary
Northwestern Medicine
Role: primary
Illinois Institute of Technology
Role: primary
Kendall Bahl
Role: primary
Melissa Harris, MPA
Role: primary
Connie Romaine, NP, RN
Role: primary
Paul Fuss
Role: primary
Jessica McGoldrick, MBA
Role: primary
Joan Thomas, MS, RD
Role: primary
Role: backup
Julie Stegall, MSW
Role: primary
Role: backup
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
AOD22022001
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
Pro00062970
Identifier Type: -
Identifier Source: org_study_id