Nutrition for Precision Health, Powered by the All of Us Research Program
Trial ID: NCT05701657
Status: RECRUITING
Study type: INTERVENTIONAL
Phase: NA
Start date: 2023-04-14
Completion date: 2027-01-31
Sponsor: RTI International
Collaborators: National Institutes of Health (NIH); University of North Carolina, Chapel Hill; Northwestern University; Illinois Institute of Technology; University of Chicago; Pennington Biomedical Research Center; Louisiana State University Health Sciences Center in New Orleans; University of California, Davis; University of California, Los Angeles; Cedars-Sinai Medical Center; University of Alabama at Birmingham; Tufts University; Massachusetts General Hospital; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Advancing Translational Sciences (NCATS); National Cancer Institute (NCI); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); City University of New York, School of Public Health; Mayo Clinic; University of California, San Diego; University of Hawaii; Vanderbilt University Medical Center; National Heart, Lung, and Blood Institute (NHLBI); National Center for Complementary and Integrative Health (NCCIH); National Institute of Drug Abuse; Public Health Informatics Computational and Operations Research; University of Southern California; Cornell University; University of Alabama, Tuscaloosa; North Carolina State University; University of North Carolina, Charlotte; Duke University; Stevens Institute of Technology; Purdue University; United States Military Academy West Point; USDA, Western Human Nutrition Research Center; North Carolina Central University; Wake Forest University Health Sciences; Boston University; Children's Hospital of Richmond; Virginia Commonwealth University; Verily Life Sciences LLC; Indiana University; Fred Hutchinson Cancer Center; Columbia University; University of Pennsylvania
Conditions: Nutrition; Health; Dietary Habits
Interventions: Diet A; Diet B; Diet C
Locations: University of Alabama at Birmingham; USDA Western Human Nutrition Research Center; University of California, Los Angeles; University of California, Davis; Cedars Sinai Medical Center; Northwestern University; Illinois Institute of Technology; University of Chicago; Pennington Biomedical Research Center; Louisiana State University Health Sciences Center; Tufts University; Massachusetts General Hospital; University of North Carolina at Chapel Hill - Chapel Hill Clinic; University of North Carolina at Chapel Hill - Kannapolis
Countries: United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States
Enrollment: 8000
Age range: 18 Years - None
Sex: ALL

Summary:
The goal of this Nutrition for Precision Health (NPH) powered by All of Us research study is to develop Artificial Intelligence/Machine Learning (AI/ML) algorithms that predict individual responses to diet patterns using rich multimodal data streams collected across multiple domains (e.g., behavior, social, environmental, clinical and molecular biomarkers). NPH includes a large phenotyping cohort (Module 1, N=8000) and two separate follow-up groups drawn from a subset of Module 1participants. One group (Module 2, N=1200) receives three distinct diets in a 14-day crossover sequence, with at least a 14-day washout period between diets, while living in their own homes. A second group (Module 3, N=150) receives the same three diets under full-time supervision in a residential research setting. We will train and test AI/ML models to predict 0-4 hour postprandial response curves for glucose, insulin, triglycerides, and GLP-1, to the standardized diet-specific meal test (DSMT) collected after each of the three different diets delivered in Module 2. Each diet functions as a controlled stimulus to reveal biological features (such as individual variables, patterns, or clusters of measurements) that best predict a person's response.

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.

Eligibility criteria:
Inclusion Criteria:

* Overall Inclusion -- Participants 18 years of age or older who have completed the primary All of Us consent process, Electronic Health Record consent process, have provided at least one All of Us biospecimen suitable for DNA sequencing, and have completed All of Us Participant Provided Information (PPI) Modules 1-3 (Basics, Overall Health, and Lifestyle); Speak English or Spanish; Able and willing to comply with study requirements and consent to participate.
* 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:

* Module 1

  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
  12. Any disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's and/or team's opinion jeopardizes the safety of the participant or others or would interfere with adherence to the protocol.
* 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)
  2. All the above mentioned exclusion criteria for Module 1 (except inability to consume components of the liquid mixed meal)
  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
  24. Any disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's opinion, might jeopardize the safety of the participant or others, or be expected to interfere with adherence to the protocol.
* Module 3

  1. All the above mentioned exclusion criteria for Modules 1 and 2
  2. Participants who are already enrolled in Module 2
  3. Any disorder, unwillingness, or inability not covered by any other exclusion criteria which, in the investigator's opinion, might jeopardize the safety of the participant or others, or would interfere with adherence to the protocol
  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

Outcomes:
Glucose - Diet Specific mixed meal tolerance test (MMTT) Diet A; Insulin - Diet Specific mixed meal tolerance test (MMTT) Diet A; Triglycerides - Diet Specific mixed meal tolerance test (MMTT) Diet A; GLP-1 - Diet Specific mixed meal tolerance test (MMTT) Diet A; Glucose - Diet Specific mixed meal tolerance test (MMTT) Diet B; Insulin - Diet Specific mixed meal tolerance test (MMTT) Diet B; Triglycerides - Diet Specific mixed meal tolerance test (MMTT) Diet B; GLP-1 - Diet Specific mixed meal tolerance test (MMTT) Diet B; Glucose - Diet Specific mixed meal tolerance test (MMTT) Diet C; Insulin - Diet Specific mixed meal tolerance test (MMTT) Diet C; Triglycerides - Diet Specific mixed meal tolerance test (MMTT) Diet C; GLP-1 - Diet Specific mixed meal tolerance test (MMTT) Diet C