Clinical trial NCT05701657: Nutrition for Precision Health, Powered by the All of Us
Official title: Nutrition for Precision Health, Powered by the All of Us Research Program
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nutrition
Health
Dietary Habits
Lead sponsor: RTI International
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: University of North Carolina, Chapel Hill
name: Northwestern University
name: Illinois Institute of Technology
name: University of Chicago
name: Pennington Biomedical Research Center
name: Louisiana State University Health Sciences Center in New Orleans
name: University of California, Davis
name: University of California, Los Angeles
name: Cedars-Sinai Medical Center
name: University of Alabama at Birmingham
name: Tufts University
name: Massachusetts General Hospital
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Center for Advancing Translational Sciences (NCATS)
name: National Cancer Institute (NCI)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: City University of New York, School of Public Health
name: Mayo Clinic
name: University of California, San Diego
name: University of Hawaii
name: Vanderbilt University Medical Center
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Complementary and Integrative Health (NCCIH)
name: National Institute of Drug Abuse
name: Public Health Informatics Computational and Operations Research
name: University of Southern California
name: Cornell University
name: University of Alabama, Tuscaloosa
name: North Carolina State University
name: University of North Carolina, Charlotte
name: Duke University
name: Stevens Institute of Technology
name: Purdue University
name: United States Military Academy West Point
name: USDA, Western Human Nutrition Research Center
name: North Carolina Central University
name: Wake Forest University Health Sciences
name: Boston University
name: Children's Hospital of Richmond
name: Virginia Commonwealth University
name: Verily Life Sciences LLC
name: Indiana University
name: Fred Hutchinson Cancer Center
name: Columbia University
name: University of Pennsylvania
First posted: 2023-01-27
Enrollment: 8000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Module 1- Response to liquid mixed meal tolerance test (LMMTT) Module 2- Dietary intervention and response to diet-specific meal test Module 3- Dietary intervention and response to diet-specific meal test and LMMTT
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this investigational study is to develop algorithms that predict human response to foods. The main question it aims to answer are:

* How does varying foods and eating patterns impact one's biological and physiological responses?
* In what ways can novel dietary assessment measures be used to improve dietary assessments and to prescribe assessments to people in future research with increased precision?
* Can artificial intelligence and machine learning techniques be combined to prescribe foods and eating patterns to individuals for optimization of their health?

There are 3 Modules participants may take part in:

* Module 1- A participant's dietary intake and accompanying nutritional status, biological and other measures will be observed over 10 days, as well as physiological responses to a liquid mixed meal tolerance test will be measured.
* Module 2- Participants will undergo three controlled dietary interventions provided for 14-days each and separated by washout periods of at least 14 days. Physiological responses following a diet-specific meal test will be measured.
* Module 3- Participants will undergo the same three dietary interventions during the same 14 day periods as Module 2 while being studied in-residence. Physiological responses following a liquid mixed meal tolerance test and a diet-specific meal test will be measured.

Detailed description: The NPH study design includes three modules: Module 1, a study of participants' dietary intake; Module 2, a randomized crossover trial with three dietary interventions among participants in a community-dwelling setting; and Module 3, a similar trial to Module 2 except with participants in residence, all detailed in the following text. Briefly, Module 1 will observe participants for 8-10 days while consuming their usual diet. Modules 2 and 3 will include 3 dietary interventions, each administered for 14 days, followed by a washout period between each diet. The study will be conducted at multiple sites managed by 6 clinical centers throughout the United States.

An interdisciplinary team of clinical nutrition research experts will evaluate dietary assessment methods, microbial metagenomics and metatranscriptomics, targeted and untargeted metabolomics, computational and data science to advance our current understanding of nutrition which will inform personalized nutrition recommendations. The resulting artificial intelligence (AI) algorithms to predict individual responses to food will provide a foundation to create customized dietary approaches to optimize short- and long-term health.

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 dietary intervention 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

Primary outcomes:
measure: Phenotypic Responses
timeFrame: 4 years
measure: Metabolomic and Microbiome Research
timeFrame: 4 years
measure: Novel Dietary Methods
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Davis
country: United States
facility: USDA Western Human Nutrition Research Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Illinois Institute of Technology
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Boston
country: United States
facility: Tufts University
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill - Chapel Hill Clinic
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill - Kannapolis
state: North Carolina
Study officials:
affiliation: RTI International
name: Marie G Gantz, PhD
role: PRINCIPAL_INVESTIGATOR
References: