Persistent Readiness Through Early Prediction Immunization Study

Study Overview
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Brief Summary
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This study will enroll volunteers in an open-format (outside hospital) setting, to complete novel data collection/analysis of biomarkers, facial images, and audio-recording to establish an optimal set of parameters to predict emergent cases of infection via an early warning score, along with actionable personalized information.

Detailed Description
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The objective of the study is to collect data from participants for a period of 4 weeks. These data will be used for developing and testing an algorithm for early detection of infection. At the end of week two, subjects will receive an immunization in a double-blind randomized placebo-controlled fashion. Vaccines to be administered will be pneumococcal (PPSV23), typhoid (inactivated), or saline. Administration of these vaccines often cause mild 'infection-like' inflammation response. Pneumococcal infection causes pneumonia and can lead to sepsis and the PPSV23 vaccination will induce mild symptoms related to the immune system activation including local reaction in 50% of the cases and fever and malaise in 1% of the cases. Typhoid fever is caused by salmonella Typhi bacteria and its effects can range from gastrointestinal symptoms to sepsis. Injectable typhoid vaccine (inactivated) side effects will induce mild symptoms related to the immune system activation and can include local reaction in 6% of the cases and fever, malaise, headache and sometimes diarrhea in 1% of the cases.

Official Title
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Persistent Readiness Through Early Prediction Immunization Study

Conditions
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Inflammatory Response

Intervention / Treatment
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* Drug: Pneumovax 23
* Drug: Typhim VI
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-40 (inclusive) Subject is judged to be in satisfactory health based on medical history, physical examination Ability to walk, sit down and stand up independently Willingness and ability to comply with the protocol ownership and use of smartphone ownership and use of laptop Exclusion Criteria: Subject has planned elective surgery requiring 2 or more days of hospitalization during the entire study Active dependence of alcohol or drugs (self-reported) Known allergy to any of the following: Components of the vaccine/placebo Diagnosed and active treatment of chronic disease: Diabetes (Type 1 or 2) Active malignancy Heart disease Kidney disease Liver disease HIV/AIDS Hepatitis A, B, or C Asthma (moderate to severe) (possible/desire to be) pregnancy (confirmed via urine pregnancy test) Subject is currently enrolled in a study with an investigational compound or device Subject has already received the pneumococcal (PPSV23) vaccine Subject has already received the typhoid (inactivated) vaccine Subject has received any other investigational vaccination within 4 weeks of enrollment Any other condition that interfere with the definition 'healthy based on self-report and according to the PI/study physician's judgement based on medical history, use of medication, and physical exam.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Parallel Assignment
Interventional Model Description: Double-blind randomized placebo-controlled vaccine administration (pneumococcal (PPSV23), typhoid (inactivated), or saline)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pneumococcal (PPSV23) vaccine<br>PNEUMOVAX 23 is a clear, colorless solution. Each 0.5-mL dose of vaccine contains 25 micrograms of each polysaccharide type in isotonic saline solution containing 0.25% phenol as a preservative under the supervision of a licensed pharmacist. | Drug: Pneumovax 23<br>* At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.<br>|
| Active Comparator: Typhoid (inactivated) vaccine<br>Typhoid vaccine is a clear, colorless solution. Each dose of 0.5 mL is formulated to contain 25 mcg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7 ± 0.3), 4.150 mg of Sodium Chloride, 0.065 mg of Disodium Phosphate, 0.023 mg of Monosodium Phosphate, and 0.5 mL of Sterile Water for Injection under the supervision of a licensed pharmacist. | Drug: Typhim VI<br>* At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.<br>|
| Placebo Comparator: Saline<br>Saline will be purchased commercially and compounded under the supervision of a licensed pharmacist in sterile syringes for administration of the placebo group. | Other: Saline<br>* At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Questionnaires, self-reported changes in general physical health, and physiological measurements to predict of type of vaccine administered | Using a daily electronic questionnaire to collect data that self-reporting changes in general physical health and physiological measurements to identify the type of intervention | up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electrocardiography Morphology | Comparison of signals from standard electrocardiography (ECG) and wearable devices measuring the time elapsed between features of the electrical activity of the heart (e.g., P-wave, PR interval, PR segment, QRS complex, QRS duration, ST segment, J point, TP interval, T-wave, U-wave, QT duration, QTc interval) | up to 4 weeks | 
| Heart Rate | Comparison of signals from standard electrocardiography (ECG) and wearable devices measuring beats per minute of the heart | up to 4 weeks | 
| Heart Rate Variability | Comparison of signals from standard electrocardiography (ECG) and wearable devices measuring variation in the time interval between consecutive heartbeats in milliseconds | up to 4 weeks | 
| Body Temperature | Comparison of signals from contact infrared forehead thermometer and wearable devices measuring body surface temperature | up to 4 weeks | 
| Blood pressure (systolic and diastolic) | Comparison of signals from standard upper arm cuff and wearable devices measuring bloodpressure | up to 4 weeks | 
| Respiratory Rate | Comparison of signals from nasal cannula and wearable devices measuring number of breaths per minute | up to 4 weeks | 
| Amount of End-tidal Carbon Dioxide | Collection from nasal cannula to measure amount of EtCO2 in exhaled breath | up to 4 weeks | 
| Oxygen Saturation | Comparison of signals from fingertip pulse oximeter and wearable devices measuring level of oxygen saturation in blood | up to 4 weeks | 
| Assessment of the type and relative abundance of protein and lipids contained in Exhaled Breath Condensate | Measurement of presence and amount of components (e.g., protein, lipids) in exhaled breath condensate as determined by liquid chromatography tandem chromatography mass spectrometry | at enrollment, and +7, +14, +16, +21, +28 days of enrollment | 
| Assessment of the type and relative abundance of Volatile Organic Compounds contained in exhaled breath | Measurement of presence and amount of volatile organic compounds (e.g., ethanol, acetone, etc) in breath by comprehensive gas chromatography mass spectrometry (GCxGC-MS) | at enrollment, and +7, +14, +16, +21, +28 days of enrollment | 
| Digital photo of the face to assess changes in general facial features | Comparison of facial features taken with on-site digital camera and mobile device to compare general facial features such as 2-D facial landmarks, 3-D head pose, Deeply embedded facial expression features, and facial expressions via tools like Mediapipe face mesh or deepface and skin tone histograms at [RGB, HSV and YCbCr] | up to 4 weeks | 
| Digital photo of the face to assess changes in eyes | Comparison of facial features taken with on-site digital camera and mobile device to compare general features of the eye such as 2-D eyes and iris landmarks and shapes, Gaze directions of two eyes, Pixel histograms of Iris, pupil, and sclera at [RGB, HSV and YCbCr], Deeply embedded iris recognition features (via tools like irisRecognition), or eye texture features (Gabor filter banks, Haralick features) using tools like Mediapipe Iris | up to 4 weeks | 
| Digital photo of the face to assess changes in other facial components | Comparison of facial features taken with on-site digital camera and mobile device to compare general features Pixel histograms of: nose, forehead, left cheek, right cheek, mouth and lips at [RGB, HSV and YCbCr] using part segmentation done with Mediapipe facemesh | up to 4 weeks | 
| Digital audio recording of vocal expressions to assess changes in vowel components | Comparison of vocal features taken with on-site digital microphone and mobile device to compare vowel components of: mean frequency (Hz), variation coefficient (%), jitter factor (%), mean intensity (dB), shimmer factor (%), and noise to harmony ratio (dB). | up to 4 weeks | 
| Digital audio recording of vocal expressions to assess frequency changes in speech prosody components | Comparison of vocal features taken with on-site digital microphone and mobile device to compare speech prosody components of: mean frequency (Hz), minimal frequency (Hz), maximal frequency (Hz), dynamic (Hz). | up to 4 weeks | 
| Digital audio recording of vocal expressions to assess variation changes in speech prosody components | Comparison of vocal features taken with on-site digital microphone and mobile device to compare speech prosody components of: median frequency variation coefficient (%), percentage of pauses (%), percentage of pauses within words (%), fragmentation of vowels (%), and stop-consonant spirantization (%). | up to 4 weeks | 
| Digital audio recording of vocal expressions to assess time domain changes in speech prosody components | Comparison of vocal features taken with on-site digital microphone and mobile device to compare speech prosody components of: mean duration of speech between two pauses (seconds), total amount of syllables (syllables/s), total amount of pure speech (syllables/s), articulation rate (syllables/s), time between pauses (s), SPIR index of rhythmicity (words/min), voice onset time (s). | up to 4 weeks | 
| Continuous Glucose Monitoring | Using the DexCom G6 continuous glucose monitoring will be done for the week prior to and following the vaccination | up to 2 weeks | 
| Changes in physical health as measured by the Medical Symptoms Questionnaire (MSQ) | The MSQ is administered by study staff for self-reporting of presence and severity of changes in symptoms in body symptoms: digestive tract, ears, emotions, energy/activity, eyes, head, heart, joint/muscles, lungs, mind, mouth/throat, nose, skin, weight, other. | +7, +14, +16, +21, +28 days of enrollment | 
| Changes in gut function as measured by Gastrointestinal Symptom Rating Scale (GSRS) | The GSRS is self-administered questionnaire regarding gut function and associated symptoms. It is composed of 15 items (7-Point Likert Scale) assessing Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation. Scores range from 15 to 105 with a higher score indicating more discomfort. | +7, +14, +16, +21, +28 days of enrollment | 
| Changes in physical activity as measured by the short International Physical Activity Questionnaire (IPAQ) | The IPAQ is a self-administered questionnaire to provide a set of well-developed instruments that can be used internationally to obtain comparable estimates of physical activity. | +7, +14, +21, +28 days of enrollment | 
| Changes in daily dietary intake as measure by the Food Frequency Questionnaire (FFQ) | The FFQ is a self-administered questionnaire to provide an estimation of dietary protein intake. | +7, +28 days of enrollment | 
| Changes in duration and quality of sleep as measured by Pittsburgh Sleep Quality Index (PSQI) | The PSQI is a self-administered questionnaire to assesses sleep quality and disturbances. 19 individual items generate seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. | +7, +28 days of enrollment | 
| Changes in physical activity as measured by the Baecke Physical Activity Questionnaire | Self-administered, 16-item questionnaire measuring physical activities in 3 categories: occupational, sport, recreational/leisure | +7, +28 days of enrollment | 
| Changes in quality of life as measured by Short Form (SF) Health Survey (SF36) | Self administered questionnaire that measures each of the following eight health concepts: Physical Functioning (PF); Role-Physical (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role-Emotional (RE); Mental Health (MH) as well as a reported Health Transition item (HT) | +7, +28 days of enrollment | 
| Renal function panel Albumin | Blood sample taken to measure Albumin | +14, +16, +21 days of enrollment | 
| Renal function panel BUN/Creatinine Ratio | Blood sample taken to measure BUN/Creatinine Ratio (calculated) | +14, +16, +21 days of enrollment | 
| Renal function panel Calcium | Blood sample taken to measure Calcium | +14, +16, +21 days of enrollment | 
| Renal function panel Carbon Dioxide | Blood sample taken to measure Carbon Dioxide | +14, +16, +21 days of enrollment | 
| Renal function panel Chloride | Blood sample taken to measure Chloride | +14, +16, +21 days of enrollment | 
| Renal function panel Creatinine | Blood sample taken to measure Creatinine | +14, +16, +21 days of enrollment | 
| Renal function panel Estimated Glomerular Filtration Rate | Blood sample taken to measure Estimated Glomerular Filtration Rate (calculated) | +14, +16, +21 days of enrollment | 
| Renal function panel Glucose | Blood sample taken to measure Glucose | +14, +16, +21 days of enrollment | 
| Renal function panel Phosphate | Blood sample taken to measure Phosphate (as Phosphorus) | +14, +16, +21 days of enrollment | 
| Renal function panel Potassium | Blood sample taken to measure Potassium | +14, +16, +21 days of enrollment | 
| Renal function panel Sodium | Blood sample taken to measure Sodium | +14, +16, +21 days of enrollment | 
| Renal function panel Urea Nitrogen | Blood sample taken to measure Urea Nitrogen | +14, +16, +21 days of enrollment | 
| Hepatic function panel Total Protein | Blood sample taken to measure Total Protein | +14, +16, +21 days of enrollment | 
| Hepatic function panel Albumin | Blood sample taken to measure Albumin | +14, +16, +21 days of enrollment | 
| Hepatic function panel Globulin (calculated) | Blood sample taken to measure Globulin (calculated) | +14, +16, +21 days of enrollment | 
| Hepatic function panel Albumin/Globulin Ratio | Blood sample taken to measure Albumin/Globulin Ratio (calculated) | +14, +16, +21 days of enrollment | 
| Hepatic function panel Total Bilirubin | Blood sample taken to measure Total Bilirubin | +14, +16, +21 days of enrollment | 
| Hepatic function panel Direct Bilirubin | Blood sample taken to measure Direct Bilirubin | +14, +16, +21 days of enrollment | 
| Hepatic function panel Indirect Bilirubin | Blood sample taken to measure Indirect Bilirubin (calculated) | +14, +16, +21 days of enrollment | 
| Hepatic function panel Alkaline Phosphatase | Blood sample taken to measure Alkaline Phosphatase | +14, +16, +21 days of enrollment | 
| Hepatic function panel Aspartate transaminase | Blood sample taken to measure Aspartate transaminase | +14, +16, +21 days of enrollment | 
| Hepatic function panel Alanine Aminotransferase | Blood sample taken to measure Alanine Aminotransferase | +14, +16, +21 days of enrollment | 
| Lipid panel | Blood sample taken to measure Total Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides, VLDL Cholesterol | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) White blood cell count | Blood sample taken to measure White blood cell count | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) red blood cell count | Blood sample taken to measure red blood cell count | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) Hemoglobin | Blood sample taken to measure Hemoglobin | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) Hematocrit | Blood sample taken to measure Hematocrit | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) mean corpuscular volume | Blood sample taken to measure mean corpuscular volume | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) mean corpuscular hemoglobin | Blood sample taken to measure mean corpuscular hemoglobin | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) corpuscular hemoglobin concentration | Blood sample taken to measure mean corpuscular hemoglobin concentration | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) red cell distribution width | Blood sample taken to measure red cell distribution width | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) Platelet Count | Blood sample taken to measure Platelet Count | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) mean platelet volume | Blood sample taken to measure mean platelet volume | +14, +16, +21 days of enrollment | 
| CBC (DIFF/PLT) Differential | Blood sample taken to measure Differential (Absolute and Percent - Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils) | +14, +16, +21 days of enrollment | 
| Highly Sensitive CRP | Blood sample taken to measure Highly Sensitive C-Reactive Protein | +14, +16, +21 days of enrollment | 
| Hemoglobin A1C | Blood sample taken to measure hemoglobin A1C | +14 days of enrollment | 
| Body Composition using Dual Energy X-Ray Absorptiometry bone density | Measurement of bone mineral density (g/cm^2) | at enrollment | 
| Body Composition using Dual Energy X-Ray Absorptiometry Muscle | Measurement of muscle mass (kg) | at enrollment | 
| Body Composition using Dual Energy X-Ray Absorptiometry Fat | Measurement of fat mass (kg) | at enrollment | 
| Measurement of daily physical activity using accelerometry sensors | Changes in physical activity detected by accelerometry data of wearable devices | up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarkers, commercial off the shelf wearable devices, large-scale machine learning, early warning of infection, predictive model of illness severity, predictive model of recovery