Restoring Molecular Circadian Rhythm

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Suspended
• CT.gov ID: NCT04086589
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Anticipated Duration (Months): 52
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy Young; Healthy Elderly	Other: Observational study without intervention

Study Design

• Study Type: Observational
• Anticipated Enrollment: 40 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Exploratory Pilot Study to Discover Genes That Restore the Molecular Circadian Rhythm
• Actual Study Start Date: Aug 18, 2019
• Anticipated Primary Completion Date: Dec 17, 2022
• Anticipated Study Completion Date: Dec 17, 2023

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. 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) [Time point 14:00 Hours]

   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

2. Delta of phase measured in HH:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults) [Time point 14:00 Hours]

   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)

Secondary Outcome Measures

1. Chronotype [4 weeks]

   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

2. Acrophase [7 days]

   Clock hour of peak physical activity averaged from 7 or more days of actigraphy

3. Physical activity [7 days]

   Vector magnitude of physical activity averaged from 7 or more days of actigraphy

4. Sleep quantity [7 or more days]

   Hours of sleep averaged from 7 or more days of actigraphy

5. Sleep quality: actigraphy [7 days]

   Sleep fragmentation averaged from 7 or more days of actigraphy

6. Ambient light exposure [7 days]

   Ambient light exposure averaged from 7 or more days of actigraphy

7. Heart rate variability [24 hours]

   Heart rate variability (RR intervals) averaged from 24 hours of BioPatch

8. Saliva cortisol [24 hours]

   Difference in concentrations of cortisol measured in saliva between morning versus evening

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04086589
• Other Study ID Numbers: 832866
• First Posted: Sep 11, 2019
• Last Update Posted: Jan 28, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Pennsylvania: healthy, young, elderly

Study Results

No Results Posted as of Jan 28, 2022