Exploratory Study of Circadian Relationships Between Social Behavior, Blood Pressure and Metabolomics

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02249793
• Collaborator: Ginger.io (Industry)
• Enrollment: 6
• Location: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

As citizens of the information age, humans leave digital traces of behavior in their communication and movement patterns through our cell phone. The Global Positioning System (GPS) technology tracks the way persons commute to school or work or when visiting family and friends. Circadian rhythmicity describes the concept that many of the bodily functions follow a roughly 24-hour rhythm. Usually, the ability to do concentrated and focused work is best during daytime while humans rest and sleep during nighttime. The current study wishes to look for a relationship between patterns in participants' cell phone use (Android only at this point) and several of their bodily functions.

Condition or Disease	Intervention/Treatment	Phase
Healthy

Detailed Description

Cell phones with internet access (so-called smartphones) represent a rich source for user activity data. Each time one places a call, sends a text message, or uses an app, a data trace is being produced which overall reflects the user's social activity and behavior. This data is called 'social sensing data'. Researchers connected this type of data to the health status of the person operating the cell phone. An example is that an outbreak of seasonal flu may lead to fewer calls and text messages among cell phone users. Thus, the social sensing data may show for example how severe an outbreak is and how fast it is spreading.

"Circadian rhythmicity" describes the concept that many of the bodily functions follow a roughly 24-hour rhythm. Usually, the ability to do concentrated and focused work is best during daytime while rest and sleep occurs during nighttime. A disturbance of this pattern, for example by regular nightshift work, may lead to an increased disease risk, such as for the cardiovascular system, the heart and blood vessels. Natural factors within a body produce our 24-hour rhythm. This rhythm is affected by outside cues such as sunlight. Jet lag is a short-term form of a disturbed 24-hour rhythm. When a person travels fast through several time zones, by plane for example from the East to the West Coast of the US, s/he arrives with a time difference of 3 hours. Upon arrival, the body runs still at East Coast time, but is exposed to the environmental cues following the West Coast time, which may make the person feel groggy and disoriented at first. Within a couple of days the body time usually adjusts and the complaints discontinue.

The current study wishes to look for a relationship between patterns in the participant's cell phone use (Android only at this point) and several of the bodily functions. As bodily functions the investigators will measure blood pressure and breakdown products (metabolites) in urine, blood and saliva samples. The investigators will collect stool samples and use swabs to collect the microbes inhabiting the mouth as well as the rectum. The investigators will also measure messenger ribonucleic acid (mRNA), messenger products of the participant's heritable information, in the blood. A cell phone application called "Ginger.io" will collect the participants' cell phone usage information. This application will also ask the participant several questions during the installation, during participation as well as at the end. Furthermore, the investigators will ask the participant about the dietary intake and habits.

The aim is to learn how the 24-hour rhythm is connected to the social activity and behavior as well as blood pressure and metabolites as markers for the health status.

Study Design

• Study Type: Observational
• Actual Enrollment: 6 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Exploratory Study in Healthy Volunteers to Define Circadian Relationships Between Social Behavior, Blood Pressure and Metabolomics
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Study group Healthy volunteers

Outcome Measures

Primary Outcome Measures

1. Calls and Text Messages [3-4 months]

   Aggregate communication as behavioral features has been collected using the cell phone data streams.

2. Changes Over Time in Ambulatory Blood Pressure - Systolic Blood Pressure [48 hours]

   Ambulatory blood pressure monitoring

3. Percentage of Total Metabolites [48 hours]

   Percentage of metabolites displaying different abundances in biosamples collected during the morning hours versus evening hours. Analysis was performed for all participants as a group.

4. Mobility Radius [3-4 months]

   The approximate radius of an imaginary circle encompassing the various locations that a user has traveled across on a particular day (in miles)

5. Calls [3-4 months]

   Number of phone calls placed and received

6. Changes Over Time in Ambulatory Blood Pressure - Diastolic Blood Pressure [48 hours]

   Ambulatory blood pressure monitoring

7. Unanswered Calls [3-4 months]

   The number of calls unanswered.

8. Unique Contacts [3-4 months]

   The total number of unique individuals with whom a participant interacted through phone calls or sms messages indicating interaction diversity

9. Call Duration [3-4 months]

   The duration of calls (made + received)

10. Text Message Length [3-4 months]

    The total length of all sms messages (sent + received) in characters

11. Text Messages [3-4 months]

    The number of sms messages (sent + received)

Secondary Outcome Measures

1. Self-reported Sleep Times [Survey] [3-4 months]

   Cell phone administered survey where participants indicated start and end of sleep times. From this the total hours of sleep per night was calculated.

2. Time Asleep [3-4 months]

   Hours asleep per each 24 hour period measured by actigraphy

3. Physical Activity [3-4 months]

   Difference in locomotion between wake and sleep times

4. Changes Over Time in Nutrient Intake - Energy [48 hours]

   Nutrient intake will be measured using food photography

5. Changes Over Time in Ribonucleic Acids (RNA) - ARNTL (BMAL1) Normalized to GAPDH [48 hours]

6. Genera Displaying Different Abundances Measured During Morning Versus Evening Hours in the Oral Microbiome [48 hours]

   Analysis was performed for all participants as a group.

7. Proteins Displaying Different Abundances Measured in the Morning Versus Evening Hours [48 hours]

   Analysis was performed for all participants as a group.

8. Changes Over Time in Kidney Function [48 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Volunteers must be in good health as based on medical history, physical examination, vital signs, and laboratory tests as deemed by PI;

• Volunteers are capable of giving informed consent;

• 25-35 years of age;

• Own a cell phone with internet access (smartphone with Android operating system only at this point) which installs the social sensing application ginger.io;

• Non-smoking;

• Male subjects only if feasible during recruitment; and

• In case female volunteers are invited to enroll: non-pregnant, female subjects must consent to a urine pregnancy test.

Exclusion Criteria:

• Recent travel across time zones (within the past month);

• Planned travel across time zones during the planned study activities;

• Volunteers with irregular work hours, e.g. night shifts.

• Use of illicit drugs;

• Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.

• Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Ginger.io

Investigators

• Principal Investigator: Carsten Skarke, MD, University of Pennsylvania
• Principal Investigator: Garret A FitzGerald, MD, University of Pennsylvania
• Principal Investigator: Aalim Weljie, PhD, University of Pennsylvania

Study Documents (Full-Text)

• Informed Consent Form - Jul 11, 2014
• Study Protocol and Statistical Analysis Plan - Jul 11, 2014

More Information

Additional Information:

• Zenodo data repository

Publications

None provided.

• Responsible Party: Carsten Skarke, MD, Research Assistant Professor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02249793
• Other Study ID Numbers: 817759
• First Posted: Sep 26, 2014
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Carsten Skarke, MD, Research Assistant Professor, University of Pennsylvania: circadian; oscillation; clock; human; social behavior; cell phone with internet access (so-called smartphone); social sensing; behavioral feature; Ginger.io; blood pressure; metabolism; metabolomics; gut bacteria; microbiome

Study Results

Participant Flow

Recruitment Details	Study Started 9/24/14, Ended 3/11/15 located at the Clinical and Translational Research Center, CTRC located at the University of Pennsylvania Hospital

Arm/Group Title	Session 1, 48-hour
Arm/Group Description	Healthy volunteers; The observation time for the biosensor-derived data was a total of four months with two 48-hour sessions (Session 1 & 2) scheduled two weeks apart to extend the biosensor platform by ambulatory blood pressure monitoring (ABPM) and timestamped dietary intake (SmartIntake) as well as by collection of timed biospecimens for multiomics analysis at 12-hour intervals.
Period Title: Session 1, 48-hours Healthy Volunteers
STARTED	6
COMPLETED	6
NOT COMPLETED	0
Period Title: Session 1, 48-hours Healthy Volunteers
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Male Healthy Volunteers
Arm/Group Description	Males
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 50%
More than one race	2 33.3%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Calls and Text Messages
Description	Aggregate communication as behavioral features has been collected using the cell phone data streams.
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	18.7
Sleeping	0.9

2. Primary Outcome

Title	Changes Over Time in Ambulatory Blood Pressure - Systolic Blood Pressure
Description	Ambulatory blood pressure monitoring
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Difference Day versus Night	20.7 (3.9)
Awake	126.1 (10.6)
Asleep	106.8 (11.6)

3. Primary Outcome

Title	Percentage of Total Metabolites
Description	Percentage of metabolites displaying different abundances in biosamples collected during the morning hours versus evening hours. Analysis was performed for all participants as a group.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Plasma metabolome	5.4
Saliva metabolome	5.6

4. Primary Outcome

Title	Mobility Radius
Description	The approximate radius of an imaginary circle encompassing the various locations that a user has traveled across on a particular day (in miles)
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Mean (Full Range) [miles]	6.8

5. Primary Outcome

Title	Calls
Description	Number of phone calls placed and received
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	2.7
Sleeping	0.1

6. Primary Outcome

Title	Changes Over Time in Ambulatory Blood Pressure - Diastolic Blood Pressure
Description	Ambulatory blood pressure monitoring
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Difference Day versus Night	20.7 (3.3)
Awake	78.5 (9.1)
Asleep	58.8 (10.2)

7. Primary Outcome

Title	Unanswered Calls
Description	The number of calls unanswered.
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	0.6
Sleeping	0.03

8. Primary Outcome

Title	Unique Contacts
Description	The total number of unique individuals with whom a participant interacted through phone calls or sms messages indicating interaction diversity
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	7.2
Sleeping	0.5

9. Primary Outcome

Title	Call Duration
Description	The duration of calls (made + received)
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	820.4
Sleeping	22.0

10. Primary Outcome

Title	Text Message Length
Description	The total length of all sms messages (sent + received) in characters
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	868.0
Sleeping	47.0

11. Primary Outcome

Title	Text Messages
Description	The number of sms messages (sent + received)
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	16.0
Sleeping	0.8

12. Secondary Outcome

Title	Self-reported Sleep Times [Survey]
Description	Cell phone administered survey where participants indicated start and end of sleep times. From this the total hours of sleep per night was calculated.
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Session 1, 48-hour
Arm/Group Description	Healthy volunteers; The observation time for the biosensor-derived data was a total of four months with two 48-hour sessions (Session 1 & 2) scheduled two weeks apart to extend the biosensor platform by ambulatory blood pressure monitoring (ABPM) and timestamped dietary intake (SmartIntake) as well as by collection of timed biospecimens for multiomics analysis at 12-hour intervals.
Measure Participants	6
Mean (Standard Deviation) [hour]	7.6 (2.9)

13. Secondary Outcome

Title	Time Asleep
Description	Hours asleep per each 24 hour period measured by actigraphy
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Mean (Standard Deviation) [hours]	7.931449224 (0.7044404472)

14. Secondary Outcome

Title	Physical Activity
Description	Difference in locomotion between wake and sleep times
Time Frame	3-4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Awake	1904.0
Sleeping	307.2

15. Secondary Outcome

Title	Changes Over Time in Nutrient Intake - Energy
Description	Nutrient intake will be measured using food photography
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Session 1	1967 (488)
Session 2	1609 (601)

16. Secondary Outcome

Title	Changes Over Time in Ribonucleic Acids (RNA) - ARNTL (BMAL1) Normalized to GAPDH
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Morning	23.3 (13.5)
Evening	17.9 (9.4)

17. Secondary Outcome

Title	Genera Displaying Different Abundances Measured During Morning Versus Evening Hours in the Oral Microbiome
Description	Analysis was performed for all participants as a group.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Number [genera]	3

18. Secondary Outcome

Title	Proteins Displaying Different Abundances Measured in the Morning Versus Evening Hours
Description	Analysis was performed for all participants as a group.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Healthy volunteers
Measure Participants	6
Number [Proteins]	2

19. Secondary Outcome

Title	Changes Over Time in Kidney Function
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Kidney function was done to evaluate healthy volunteers during Session 1 and 2. Delta was calculated between Session 1 and 2 and averaged across subjects. Note that values for session1 was missing for two subjects, meaning that below reported mean and standard deviation reflect changes for four subjects.

Arm/Group Title	Session 1, 48-hour
Arm/Group Description	Healthy volunteers; The observation time for the biosensor-derived data was a total of four months with two 48-hour sessions (Session 1 & 2) scheduled two weeks apart to extend the biosensor platform by ambulatory blood pressure monitoring (ABPM) and timestamped dietary intake (SmartIntake) as well as by collection of timed biospecimens for multiomics analysis at 12-hour intervals.
Measure Participants	6
Mean (Standard Deviation) [mg/dL]	12.925 (115.468246)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	All non serious AE were resolved, Serious AE: None
Arm/Group Title	Healthy Volunteers
Arm/Group Description	Males
All Cause Mortality
	Healthy Volunteers
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Healthy Volunteers
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Volunteers
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
General disorders
headache	1/6 (16.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.