Persistent Readiness Through Early Prediction Immunization Study (PREP DOD)

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.

Study Overview

• Status: Completed
• Conditions: Inflammatory Response
• Intervention / Treatment: Drug: Pneumovax 23; Drug: Typhim VI; Other: Saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 249
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • College Station, Texas, United States, 77845
      • Texas A&M University - CTRAL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pneumococcal (PPSV23) vaccine; 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; At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.
ACTIVE_COMPARATOR: Typhoid (inactivated) vaccine; 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; At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.
PLACEBO_COMPARATOR: Saline; 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; At +14 days from enrollment in the trial, participants will receive a vaccine administered via intramuscular route only.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of personalized algorithm to provide an estimate of probability of onset of infection using activity and physiological measures	Apply machine learning algorithms to data collected from clinical setting and wearable devices at various time scales relative to symptoms that are represented by percent score between 0-100%.	through study completion, up to 4 weeks
Development of personalized algorithm to provide an estimated index of severity of infection using activity and physiological measures	Apply machine learning algorithms to data collected from clinical setting and wearable devices at various time scales relative to symptoms to estimate the acuity/intensity of care associated with infection ranging from 0-10.	through study completion, up to 4 weeks
Development of personalized algorithm to provide an estimated score related to time until recovery of infection using activity and physiological measures	Apply machine learning algorithms to data collected from clinical setting and wearable devices at various time scales relative to symptoms to be reported in hours.	through study completion, up to 4 weeks
Development of personalized algorithm to provide detect the systems involved (respiratory vs gastrointestinal vs other) in infection using activity and physiological measures	Apply machine learning algorithms to data collected from clinical setting and wearable devices at various time scales relative to symptoms to generate a probability score of systems involved in infection.	through study completion, up to 4 weeks

Collaborators and Investigators

• Sponsor: Texas A&M University
• Collaborators: Philips Healthcare; US Department of Defense - Defense Threat Reduction Agency

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2022
• Primary Completion (ACTUAL): December 21, 2022
• Study Completion (ACTUAL): December 21, 2022

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (ACTUAL): April 26, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; commercial off the shelf wearable devices; large-scale machine learning; early warning of infection; predictive model of illness severity; predictive model of recovery
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: PREP DOD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No