Restoring Molecular Circadian Rhythm

Exploratory Pilot Study to Discover Genes That Restore the Molecular Circadian Rhythm

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).

Study Overview

• Status: Suspended
• Conditions: Healthy Elderly; Healthy Young
• Intervention / Treatment: Other: Observational study without intervention

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Apparent healthy volunteers

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Young; Observational study without intervention	Other: Observational study without intervention; Observational study without intervention
Elderly; Observational study without intervention	Other: Observational study without intervention; Observational study without intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	To determine if serum collected from young versus old healthy study participants have a differential effect on the expression of circadian rhythms in an in vitro culture of a fibroblast cell line	Time point 14:00 Hours
Delta of phase measured in HH:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults)	The primary endpoint will be the difference in phase angle in vitro between cycling fibroblasts and incubated with serum collected from cases (old adults) versus controls (young adults)	Time point 14:00 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronotype	Assessed per survey; chronotypes per Munich Chronotype questionnaire are extreme early type, moderate early type, slight early type, normal type, slight late type, moderate late type, extreme late type	4 weeks
Acrophase	Clock hour of peak physical activity averaged from 7 or more days of actigraphy	7 days
Physical activity	Vector magnitude of physical activity averaged from 7 or more days of actigraphy	7 days
Sleep quantity	Hours of sleep averaged from 7 or more days of actigraphy	7 or more days
Sleep quality: actigraphy	Sleep fragmentation averaged from 7 or more days of actigraphy	7 days
Ambient light exposure	Ambient light exposure averaged from 7 or more days of actigraphy	7 days
Heart rate variability	Heart rate variability (RR intervals) averaged from 24 hours of BioPatch	24 hours
Saliva cortisol	Difference in concentrations of cortisol measured in saliva between morning versus evening	24 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Carsten Skarke, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Estimated): July 17, 2024
• Study Completion (Estimated): December 17, 2024

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: healthy, young, elderly
• Other Study ID Numbers: 832866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No