Interventional Testing of Gene-environment Interactions Via the Verifomics Mobile Application

Study Overview
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Brief Summary
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The purpose of this study is to study interactions between genes, lifestyle environmental factors like foods, nutritional supplements and non-invasive medical devices and health factors that can be measured without specialized medical equipment in order to develop lifestyle recommendations tailored to individual genetics for a host of common chronic health conditions.

Detailed Description
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The study is composed of multiple interventions which will last between 2 and 6 months that evaluate a suite of predictions about the way that a given environmental factor impacts a specific health outcome based on genetic information obtained from direct-to-consumer genotyping providers (AncestryDNA and 23andMe). Substances of interest include foods, nutritional supplements and non-invasive medical devices. A minimum of 500 subjects will be enrolled in each intervention, and only those subjects which are predicted to benefit from the intervention when considering all sites of interest will be assigned to an intervention. The predictions are based on hundreds to thousands of sites of interest at high minor allele frequency single nucleotide polymorphisms and predictions about response are derived from the aggregate genotype at all loci considered. As such each site of interest will have a built-in negative control group composed of individuals enrolled in the intervention despite a genotype at that site that does not predict a benefit. The rate that each site of interest makes correct predictions about subject response will be compared to randomly-selected sites in order to quantify placebo effects and establish quality metrics for the predictions. Enrollment and participation are conducted remotely. Participants will upload genetic information from a direct-to-consumer provider through a mobile or web browser application, and informed consent and inclusion/exclusion criteria are accomplished remotely. After the informed consent process, participants are asked what phenotype of interest (weight, migraines, insomnia, etc.) they are interested in studying, their genetic information is evaluated and they are allowed to select an intervention they qualify for based on their genetics that they would like to participate in. Participants then answer a series of questions to establish baseline data on relevant factors as well as evaluate the inclusion and exclusion criteria; participants that qualify for the intervention are then given specific instructions on how to participate, and may then use the software to report data during the intervention. Each intervention utilizes a specific product rather than a general class of product to reduce noise from differing sourcing, distribution, storage and manufacturing practices.

Official Title
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Interventional Testing of Gene-environment Interactions Via the Verifomics Mobile Application

Conditions
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Obesity, Arthritis, Rhinitis, Rhinitis, Allergic, Respiratory Sounds, Dyspnea, Headache, Migraine Disorders, Arthralgia, Anxiety, Sleep Initiation and Maintenance Disorders, Sleep Deprivation

Intervention / Treatment
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* Dietary Supplement: Vitamin A
* Dietary Supplement: Vitamin B6
* Dietary Supplement: Vitamin C
* Dietary Supplement: Nicotinamide
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin E
* Other: Broccoli
* Other: Spinach
* Dietary Supplement: Caffeine
* Other: Coffee
* Device: Axon Eyewear
* Other: Chocolate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For BMI interventions, BMI > 25 For headache interventions, more than 2 headache-days per month For insomnia interventions, at least one day of self-reported poor sleep per week For rhinitis interventions, more than 2 days with symptoms per month For joint pain interventions, at least one day of self-reported joint pain per week Exclusion Criteria: Women who are pregnant, nursing or attempting to become pregnant Immediately life-threatening disease Current use of nutritional supplements of interest (excluded from those interventions to prevent overdose) For spinach interventions, gout

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Predictions: BMI vs. Broccoli<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Broccoli<br>* Subjects will be asked to increase broccoli intake by 8 fluid ounces ( 91 grams) per day.<br>* Other names: Brassica oleracea;|
| Experimental: Predictions: BMI vs. Caffeine<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Caffeine<br>* Subjects will be asked to increase caffeine intake by taking 200mg caffeine orally once per day.<br>* Other names: 1,3,7-Trimethylpurine-2,6-dione;|
| Experimental: Predictions: BMI vs. Coffee<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Coffee<br>* Subjects will be asked to increase coffee intake by drinking 2 cups (177 mL each) of coffee per day.<br>|
| Experimental: Predictions: BMI vs. Spinach<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Spinach<br>* Subjects will be asked to increase spinach intake by 8 fluid ounces ( 30 grams) per day.<br>* Other names: Spinacia oleracea;|
| Experimental: Predictions: BMI vs. Vitamin A<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin A<br>* Subjects will be asked to increase vitamin A intake by 8000 International Units per day.<br>* Other names: Retinoic acid;|
| Experimental: Predictions: BMI vs. Vitamin C<br>BMI will be calculated from self-reported weight (once per day) and height (at enrollment). Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin C<br>* Subjects will be asked to increase vitamin C intake by 500 mg per day.<br>* Other names: Ascorbic acid;|
| Experimental: Predictions: Headache vs. Vitamin B6<br>Headache frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin B6<br>* Subjects will be asked to increase vitamin B6 intake by 50 mg per day.<br>* Other names: Pyridoxine;|
| Experimental: Predictions: Headache vs. Vitamin C<br>Headache frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin C<br>* Subjects will be asked to increase vitamin C intake by 500 mg per day.<br>* Other names: Ascorbic acid;|
| Experimental: Predictions: Headache vs. Nicotinamide<br>Headache frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Nicotinamide<br>* Subjects will be asked to increase Nicotinamide intake by 500 mg per day.<br>* Other names: Niacinamide;|
| Experimental: Predictions: Headache vs. Axon Eyewear<br>Headache frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Device: Axon Eyewear<br>* Subjects will be asked to utilize the therapeutic eyewear when exposed to bright or fluorescent light.<br>|
| Experimental: Predictions: Rhinitis vs Broccoli<br>Rhinitis frequency and severity will be self-reported on a scale from 0 to 10, with 0 indicating no rhinitis, 3 indicating minor rhinitis, 6 indicating rhinitis while preserving the ability to breathe nasally, and 10 indicating rhinitis to such a degree that mouth-breathing is required, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Broccoli<br>* Subjects will be asked to increase broccoli intake by 8 fluid ounces ( 91 grams) per day.<br>* Other names: Brassica oleracea;|
| Experimental: Predictions: Rhinitis vs Caffeine<br>Rhinitis frequency and severity will be self-reported on a scale from 0 to 10, with 0 indicating no rhinitis, 3 indicating minor rhinitis, 6 indicating rhinitis while preserving the ability to breathe nasally, and 10 indicating rhinitis to such a degree that mouth-breathing is required, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Caffeine<br>* Subjects will be asked to increase caffeine intake by taking 200mg caffeine orally once per day.<br>* Other names: 1,3,7-Trimethylpurine-2,6-dione;|
| Experimental: Predictions: Rhinitis vs Chocolate<br>Rhinitis frequency and severity will be self-reported on a scale from 0 to 10, with 0 indicating no rhinitis, 3 indicating minor rhinitis, 6 indicating rhinitis while preserving the ability to breathe nasally, and 10 indicating rhinitis to such a degree that mouth-breathing is required, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Chocolate<br>* Subjects will be asked to increase chocolate intake by eating 57g per day.<br>|
| Experimental: Predictions: Rhinitis vs Coffee<br>Rhinitis frequency and severity will be self-reported on a scale from 0 to 10, with 0 indicating no rhinitis, 3 indicating minor rhinitis, 6 indicating rhinitis while preserving the ability to breathe nasally, and 10 indicating rhinitis to such a degree that mouth-breathing is required, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Coffee<br>* Subjects will be asked to increase coffee intake by drinking 2 cups (177 mL each) of coffee per day.<br>|
| Experimental: Predictions: Rhinitis vs Vitamin A<br>Rhinitis frequency and severity will be self-reported on a scale from 0 to 10, with 0 indicating no rhinitis, 3 indicating minor rhinitis, 6 indicating rhinitis while preserving the ability to breathe nasally, and 10 indicating rhinitis to such a degree that mouth-breathing is required, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin A<br>* Subjects will be asked to increase vitamin A intake by 8000 International Units per day.<br>* Other names: Retinoic acid;|
| Experimental: Predictions: Insomnia vs Axon Eyewear<br>Sleep quality will be self-reported about the previous night's sleep on a scale from 0 to 10, with 0 indicating sleep that was not restful at all, 3 indicating mildly restful but insufficient sleep, 6 indicating a functional quality of sleep but not ideal, and 10 indicating ideal sleep, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Device: Axon Eyewear<br>* Subjects will be asked to utilize the therapeutic eyewear when exposed to bright or fluorescent light.<br>|
| Experimental: Predictions: Insomnia vs Vitamin A<br>Sleep quality will be self-reported about the previous night's sleep on a scale from 0 to 10, with 0 indicating sleep that was not restful at all, 3 indicating mildly restful but insufficient sleep, 6 indicating a functional quality of sleep but not ideal, and 10 indicating ideal sleep, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin A<br>* Subjects will be asked to increase vitamin A intake by 8000 International Units per day.<br>* Other names: Retinoic acid;|
| Experimental: Predictions: Insomnia vs Vitamin E<br>Sleep quality will be self-reported about the previous night's sleep on a scale from 0 to 10, with 0 indicating sleep that was not restful at all, 3 indicating mildly restful but insufficient sleep, 6 indicating a functional quality of sleep but not ideal, and 10 indicating ideal sleep, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin E<br>* Subjects will be asked to increase vitamin E intake by 400 International Units per day.<br>* Other names: α-tocopherol;|
| Experimental: Predictions: Insomnia vs Nicotinamide<br>Sleep quality will be self-reported about the previous night's sleep on a scale from 0 to 10, with 0 indicating sleep that was not restful at all, 3 indicating mildly restful but insufficient sleep, 6 indicating a functional quality of sleep but not ideal, and 10 indicating ideal sleep, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Nicotinamide<br>* Subjects will be asked to increase Nicotinamide intake by 500 mg per day.<br>* Other names: Niacinamide;|
| Experimental: Predictions: Insomnia vs Vitamin D3<br>Sleep quality will be self-reported about the previous night's sleep on a scale from 0 to 10, with 0 indicating sleep that was not restful at all, 3 indicating mildly restful but insufficient sleep, 6 indicating a functional quality of sleep but not ideal, and 10 indicating ideal sleep, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Vitamin D3<br>* Subjects will be asked to increase Vitamin D3 intake by 1000 International Units per day.<br>* Other names: Cholecalciferol;|
| Experimental: Predictions: Joint pain vs Broccoli<br>Joint pain frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Broccoli<br>* Subjects will be asked to increase broccoli intake by 8 fluid ounces ( 91 grams) per day.<br>* Other names: Brassica oleracea;|
| Experimental: Predictions: Joint pain vs Caffeine<br>Joint pain frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Dietary Supplement: Caffeine<br>* Subjects will be asked to increase caffeine intake by taking 200mg caffeine orally once per day.<br>* Other names: 1,3,7-Trimethylpurine-2,6-dione;|
| Experimental: Predictions: Joint pain vs Coffee<br>Joint pain frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Coffee<br>* Subjects will be asked to increase coffee intake by drinking 2 cups (177 mL each) of coffee per day.<br>|
| Experimental: Predictions: Joint pain vs Spinach<br>Joint pain frequency and severity will be evaluated via a graphical and written pain scale, reported once per day. Each gene-environment interaction of interest will be evaluated to determine its predictive power. | Other: Spinach<br>* Subjects will be asked to increase spinach intake by 8 fluid ounces ( 30 grams) per day.<br>* Other names: Spinacia oleracea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of correct predictions | Each site of interest is being evaluated for its ability to make correct predictions about subject response. This frequency will be compared via a variety of statistical techniques to that expected by chance to establish its clinical utility. | Assessed 30 days after enrollment, comparing values of phenotypes of interest in the final week of the intervention to the value at enrollment and determining if the actual response is consistent with the prediction made prior to enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genotype-independent effects of substances of interest | Baseline responses to environmental factors studied in terms of phenotypes of interest are measured to remove this potential bias from the analysis of predictive power. | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in body mass index |  | Assessed 30 days after enrollment, comparing value at enrollment to value after 30 days of participation | 
| Change in headache severity |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in headache frequency |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in rhinitis severity |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in rhinitis frequency |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in insomnia frequency |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in insomnia severity |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in joint pain severity |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Change in joint pain frequency |  | Assessed 30 days after enrollment, comparing value at enrollment to value after in the final week of participation | 
| Question of the day questionnaire | Asynchronous longitudinal observations about subject health, diet, environment, lifestyle and anecdotal observations to be used to guide future studies, control for co-linear changes in behavior, monitor for serendipitous events and assess environment-environment interactions. Subjects are asked to answer one question from the survey per day, and questions are asked recurrently at question-specific intervals. | Daily for the duration of participation (2 to 6 months), starting on the day of enrollment and ending when the intervention is concluded, either because the scientific endpoints are met or the subjects voluntarily halt participation.. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food, Nutrigenomics, Precision Medicine, Pharmacogenetics, Lifestyle