2021 PMT iAge® Intervention Trial by Edifice Health

Study Overview
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Brief Summary
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This is a decentralized, double-blind, randomized, placebo-controlled study to assess the effectiveness of different dietary supplements in decreasing systemic chronic inflammation (SCI) and lowering inflammatory age (iAge®). iAge® is a metric for age-related chronic inflammation and immune function decline calculated from a standard blood draw utilizing immune phenotyping and artificial intelligence algorithms. SCI is a natural process that occurs within the body. It is believed to accelerate the process of biological aging. As opposed to acute inflammation, iAge® is not a reflection of illness, infection, trauma or injury. It naturally occurs in the ambulatory healthy population as we age as a function of the body. This study will use immunotype specific dietary supplement formulations to improve a participant's Inflammatory Age® (iAge®).

Detailed Description
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This decentralized, double-blind, randomized, placebo-controlled study will identify interventions that may lower a participant's inflammatory age (iAge®) and will increase the number of participants with objective and subjective health information that have associated iAge® scores. The study will also (1) correlate secondary endpoints with baseline and subsequent iAge® scores, (2) confirm the compatibility of the iAge® test with the Tasso device, ADX100 or ViveBio home blood collection systems, and (3) confirm the compatibility of the iAge® test with saliva home sample collection kit. Ambulatory adults, 18 years old and over of diverse ethnicities will be invited to participate in this study from a single site in Marin County. We will choose an equal number of male and female participants by selecting households within a 60 mile radius of the study site. The study involves fasting blood sample collection to measure and characterize immunomes and inflammatory biomarkers, metabolites, lipid panel, hemoglobin, hemoglobin A1C, and high-sensitivity c-reactive protein (hsCRP). Participants will be asked to provide a blood sample by routine venipuncture at Baseline and approximately 2, 4 and 7 months after the start of the dietary supplement/placebo. Participants will be given interventions to be taken daily based on their associated immunogroup cluster after each iAge® test is completed. Participants can continue on their current supplements but should not start any new supplements except those given by the study. This study has a different intervention for nine of the ten immunotype clusters. All interventions are i) generally recognized as safe (GRAS) or ii) from compounds at similar concentrations to those found in foods. Participants will be placed in one of ten immunotype clusters after each iAge® test and randomized either to a placebo or the given formulation to be taken once daily (either one, two or three pills depending on the formulation). A participant who changes his/her immunotype cluster after a follow up iAge® test will be given a new dietary intervention (or placebo based on their previous category). All participants will also be given a Whoop wearable watch to collect information on strain, sleep and heart rate variability. Participants will be asked to complete questionnaires assessing mood, stress level, well-being, cognition, health and lifestyle. We will also obtain the following measurements: (1) Height and weight, (2) blood pressure, (3) waist and hip measurements, (4) pulse wave velocity (PWV) to measure arterial stiffness (5) timed up and go to assess frailty and (6) facial and scalp photos. A gut microbiome sampling using a third party kit for fecal collection will be obtained at each designated time point from those participants who agree to have fecal sample collection. A subset of participants will have the following procedures done at any time point during the study: (1) saliva collection, (2) heel bone density, (3) audiometry test, (4) home blood sample collection using the Tasso device, ADX100, and ViveBio device.

Official Title
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Randomized, Double-Blinded, Placebo-Controlled Study With Immunotype Specific Dietary Supplements to Improve Inflammatory Age® by Edifice Health

Conditions
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Chronic Inflammation, Inflammaging

Intervention / Treatment
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* Dietary Supplement: Dietary supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18+ years old Ambulatory Willing and able to comply with the study protocol Exclusion Criteria: Participants with any condition that may preclude venipuncture or venous blood draws will be excluded. Participants with known allergies to interventions will be removed from the study. Vulnerable subjects including children, employees and those with cognitive disabilities will not be included in this study. Male participants on iron supplementation Participants on >1 mg manganese, >5 mg biotin Pregnant women Nursing women Membership in the clinical study team Any condition that might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol At the time of enrollment: Active systemic or serious concurrent illness History of immunodeficiency Any known or suspected impairment of immunologic function Diabetes mellitus treated with any diabetic medication Moderate to severe renal disease Blood pressure greater than 140/90 Chronic hepatitis B or C Recent or current use of immunosuppressive medication Malignancy other than squamous cell or basal cell skin cancer, including solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia, which might jeopardize volunteer safety or compliance with the protocol Autoimmune disease Auto-inflammatory disease History of blood dycrasias or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year Use of any anticoagulation medication A medical or psychiatric condition or occupational responsibilities that would preclude subject compliance with the protocol History of Guillain-Barre syndrome

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Participants will receive a formulation of dietary supplements based on the iAge test. Different formulations contain different combinations of dietary supplements.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dietary supplements<br>Dietary supplements are either (1) designated as Generally Recognized As Safe (GRAS) by the Food and Drug Administration or (2) compounds at similar concentrations to those found in foods. | Dietary Supplement: Dietary supplement<br>* iron bisglycinate manganese chloride vitamin D2 guar gum indole-3-carbinol L-methionine piceatannol biotin caffeine beta-carotene lutein zinc sulfate<br>|
| Placebo Comparator: Placebo<br>Placebo-matched formulations | Other: Placebo<br>* Matched Placebo to Intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inflammatory age (iAge®) scores from Baseline to end of study intervention | Measurement of iAge® scores in all study participants. Peripheral blood samples will be collected, processed and analyzed and iAge is measured using standardized procedures, immune phenotyping and artificial intelligence algorithms. | Measured at Baseline, Day 50, Day 120 and Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immune protein biomarkers from Baseline to end of study intervention | Blood sample measurements of the levels of the biomarkers Eotaxin-1 (CCL11), Interferon-gamma, Growth Regulated Oncogene-alpha, Monokine Induced by Gamma Interferon (MIG) and TNF-related Apoptosis Inducing Ligand (TRAIL) | Measured at Baseline, Day 50, Day 120 and Day 210 | 
| Change in values for hemoglobin, A1C, high sensitivity C-reactive protein (hs-CRP), and lipid panel from Baseline to end of study intervention | Blood samples measured for hemoglobin, A1C, hs-CRP, and lipid panel | Measured at Baseline, Day 50, Day 120 and Day 210 | 
| Anthropometric and metabolic measurements from Baseline to end of study intervention | Measurement of height, weight, body mass index (BMI), waist-to-hip ratio | Measured at Baseline, Day 50, Day 120 and Day 210 | 
| Change in cardiovascular health from Baseline to end of study intervention | Measurement of blood pressure, pulse wave velocity using the Whithings Cardio device and heart rate variability with the Whoop wearable | Measured at Baseline, Day 50, Day 120 and Day 210 | 
| Correlation of iAge score with ankle bone density score | Measurement of ankle bone density using the GE Achilles Lunar Express ultrasonometer | Measured at a single time point during the duration of the study | 
| Correlation of iAge score with hearing test score | Measurement of hearing acuity using the Shoebox Audiometry System | Measured at a single time point during the duration of the study | 
| Change in frailty and mobility from Baseline to end of study intervention | Timed Up and Go (TUG) test will be use to measure the length of time in seconds it takes for the participant to stand from a chair, walk 3 meters, turn around and sit back in the chair. TUG is a simple sensitive test to assess mobility, balance, walking ability, and fall risk in older adults. | Measured at Baseline and Day 210 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory age (iAge®), immunosenescence, immune phenotyping, systemic chronic inflammation