Clinical trial NCT04086589: Restoring Molecular Circadian Rhythm
Official title: Exploratory Pilot Study to Discover Genes That Restore the Molecular Circadian Rhythm
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Healthy Young
Healthy Elderly
Keywords: healthy, young, elderly
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2019-09-11
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Apparent healthy volunteers

Brief summary: The goal is to address the mechanisms that account for alteration of circadian rhythms with age. As the blood of aged individuals can produce this alteration, the investigators propose to use such blood samples to "age" circadian rhythms in cultured cells. The investigators will verify aged blood-dependent alteration of rhythms and then conduct molecular screens to reverse this decline. If the investigators identify specific genes that can restore molecular circadian rhythm in vitro, the investigators will explore these in animal models (Drosophila, mouse).


Eligibility criteria: Inclusion Criteria:

* General good health with the following conditions permissible

  * cardiovascular risk prevention, intake of low dose aspirin,
  * hypertension, intake of beta-blockers, ACE inhibitors, diuretics, calcium channel blockers
  * hypercholesterinemia, intake of statins
* Cases: 70-85 years of age
* Controls: 20-35 years of age
* Patients must be able to read and understand English
* Participants must sign the informed consent form
* Participants must have a wrist-actigraphy-based average TST (total sleep time) ≥ 6 hours per night (measured over 7 consecutive days) occurring between 22:00 - 08:00

Exclusion Criteria:

* Known history of severe psychiatric or cognitive conditions, for example mania, schizophrenia, or mental retardation
* Shift work, defined as recurring work between 22:00-05:00
* History of clinically significant obstructive sleep apnea
* Transmeridian travel across ≥2 time zones in the two weeks prior to the blood draws and one week after,
* \> 2 drinks of alcohol per day
* Use of illicit drugs

Primary outcomes:
measure: Delta of period length measured in hh:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults)
timeFrame: Time point 14:00 Hours
measure: Delta of phase measured in HH:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults)
timeFrame: Time point 14:00 Hours
Secondary outcomes:
measure: Chronotype
timeFrame: 4 weeks
measure: Acrophase
timeFrame: 7 days
measure: Physical activity
timeFrame: 7 days
measure: Sleep quantity
timeFrame: 7 or more days
measure: Sleep quality: actigraphy
timeFrame: 7 days
measure: Ambient light exposure
timeFrame: 7 days
measure: Heart rate variability
timeFrame: 24 hours
measure: Saliva cortisol
timeFrame: 24 hours
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Carsten Skarke, MD
role: PRINCIPAL_INVESTIGATOR
References: