RECRUITING

Single Nuclei RNA-seq to Map Adipose Cellular Populations and Senescent Cells in Older Subjects

Conditions

Obesity Healthy Lifestyle Lifestyle intervention Single RNA sequencing Cell Senescence

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq and metabolic/physiological assessments (insulin sensitivity, glucose tolerance, and β-cell function). Older obese participants will be randomized into three arms: lifestyle intervention (n=24), senolytics (n=24), or placebo (n=24).

Official Title

Single Nuclei RNA-sequencing to Map Adipose Cellular Populations and Senescent Cells in Older Subjects

Quick Facts

Study Start:2023-10-17

Study Completion:2027-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05653258

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Both Sexes 2. Age: younger lean group 18-30 years with BMI 18.5-24.9 kg/m2; older lean group ≥ 65 years with BMI 3. All races and ethnic groups 4. Community dwelling 5. Sedentary (≤1.5 h of exercise per week) 6. Nondiabetic (fasting plasma glucose \< 126 mg/dl, 2-h glucose during oral glucose tolerance test (OGTT) \< 140mg/dl, and A1c \< 6.5% 7. For all female participants who are women of childbearing potential (WOCBP), who are not pregnant or breast feeding, at least one of the following conditions must apply: 8. ECG value after 10 minutes of resting in the supine position in the following ranges:	1. Diabetes, clinically diagnosed or HbA1c \> 6.5% and/or fasting plasma glucose \> 126 mg/dl and/or use of anti-diabetic medications. 2. Participating in \> 1.5 h of structured exercise/week 3. Unstable weight (\>3% change in last 3 months) 4. Neurological, musculoskeletal, or other conditions that may limit subject's ability to complete study physical assessment and training 5. Active autoimmune/inflammatory disease including: rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, inflammatory bowel disease 6. Laboratory parameters outside the normal range: * impaired kidney function (eGFR \< 30ml/min/1.73m² as calculated by the CKD-EPI equation); * impaired liver function (AST or ALT level \> 2 times upper limit of normal (ULN); * total Bilirubin level \> 1.5 times ULN; * TSH \> 1.5 times ULN or \< lower limit of normal (LLN); * Hemoglobin \<10.0 g/dl; Platelets \<125,000 cell/mm³; * Platelets \< 125,000 cell/mm³ * Prothrombin time (PT) \> 1.0 times ULN * Partial prothrombin time (PTT) \> 1.0 times ULN. 7. Active gastrointestinal disease; coagulopathy; GI bleed within 6 months 8. Clinically significant heart disease (e.g. NYH Classification \>II; ischemia) 9. Peripheral vascular disease (claudication) 10. QTc prolongation \>45 msec 11. Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication (see section 5.3) 12. Use of quinolone antibiotics or any other drugs that may prolong the QTc interval (see section 5.3) 13. Pulmonary disease (COPD), severe asthma or exercise-induced asthma 14. Recent systemic or pulmonary embolus 15. Uncontrolled blood pressure (systolic BP\>170, diastolic BP\>95 mmHg) 16. Smoking, alcohol use (history of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants. 1 drink = 5 ounces \[150ml\] of wine or 12 ounces \[360ml\] of beer or 1.5 ounces \[45ml\] of hard liquor) or recreational drug use 17. Pregnant or breastfeeding 18. Postmenopausal women new (within 6 months) to systemic hormone replacement therapy 19. Previous bariatric surgery 20. History of stroke with motor disability 21. Recent (3 years) treated cancer other than basal cell carcinoma 22. Acute or chronic infection 23. Medication that might interfere with metabolic studies (weight loss medication, systemic steroids, immunosuppressants) within 6 months (see section 5.3) 24. Potentially senolytic agents within the last 6 months: fisetin, quercetin, luteolin, dasatinib, piperlongumine, or navitoclax (see section 5.3) 25. History of allergy to dasatinib, quercetin and/or lidocaine.

Inclusion Criteria

Exclusion Criteria

1. Both Sexes
2. Age: younger lean group 18-30 years with BMI 18.5-24.9 kg/m2; older lean group ≥ 65 years with BMI
3. All races and ethnic groups
4. Community dwelling
5. Sedentary (≤1.5 h of exercise per week)
6. Nondiabetic (fasting plasma glucose \< 126 mg/dl, 2-h glucose during oral glucose tolerance test (OGTT) \< 140mg/dl, and A1c \< 6.5%
7. For all female participants who are women of childbearing potential (WOCBP), who are not pregnant or breast feeding, at least one of the following conditions must apply:
8. ECG value after 10 minutes of resting in the supine position in the following ranges:

1. Diabetes, clinically diagnosed or HbA1c \> 6.5% and/or fasting plasma glucose \> 126 mg/dl and/or use of anti-diabetic medications.
2. Participating in \> 1.5 h of structured exercise/week
3. Unstable weight (\>3% change in last 3 months)
4. Neurological, musculoskeletal, or other conditions that may limit subject's ability to complete study physical assessment and training
5. Active autoimmune/inflammatory disease including: rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, inflammatory bowel disease
6. Laboratory parameters outside the normal range:
* impaired kidney function (eGFR \< 30ml/min/1.73m² as calculated by the CKD-EPI equation);
* impaired liver function (AST or ALT level \> 2 times upper limit of normal (ULN);
* total Bilirubin level \> 1.5 times ULN;
* TSH \> 1.5 times ULN or \< lower limit of normal (LLN);
* Hemoglobin \<10.0 g/dl; Platelets \<125,000 cell/mm³;
* Platelets \< 125,000 cell/mm³
* Prothrombin time (PT) \> 1.0 times ULN
* Partial prothrombin time (PTT) \> 1.0 times ULN.
7. Active gastrointestinal disease; coagulopathy; GI bleed within 6 months
8. Clinically significant heart disease (e.g. NYH Classification \>II; ischemia)
9. Peripheral vascular disease (claudication)
10. QTc prolongation \>45 msec
11. Use of anti-arrhythmic medications known to cause QTc prolongation, anti-platelet or anti-coagulant medication (see section 5.3)
12. Use of quinolone antibiotics or any other drugs that may prolong the QTc interval (see section 5.3)
13. Pulmonary disease (COPD), severe asthma or exercise-induced asthma
14. Recent systemic or pulmonary embolus
15. Uncontrolled blood pressure (systolic BP\>170, diastolic BP\>95 mmHg)
16. Smoking, alcohol use (history of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants. 1 drink = 5 ounces \[150ml\] of wine or 12 ounces \[360ml\] of beer or 1.5 ounces \[45ml\] of hard liquor) or recreational drug use
17. Pregnant or breastfeeding
18. Postmenopausal women new (within 6 months) to systemic hormone replacement therapy
19. Previous bariatric surgery
20. History of stroke with motor disability
21. Recent (3 years) treated cancer other than basal cell carcinoma
22. Acute or chronic infection
23. Medication that might interfere with metabolic studies (weight loss medication, systemic steroids, immunosuppressants) within 6 months (see section 5.3)
24. Potentially senolytic agents within the last 6 months: fisetin, quercetin, luteolin, dasatinib, piperlongumine, or navitoclax (see section 5.3)
25. History of allergy to dasatinib, quercetin and/or lidocaine.

Contacts and Locations

Study Contact

Nicolas Musi, MD

CONTACT

210-562-6140

nicolas.musi@cshs.org

Monica Serra, PhD

CONTACT

20-562-5040

serram@uthscsa.edu

Principal Investigator

Nicolas Musi, MD

PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Study Locations (Sites)

Cedars Sinai Medical Center

Los Angeles, California, 90048

United States

Collaborators and Investigators

Sponsor: Cedars-Sinai Medical Center

Nicolas Musi, MD, PRINCIPAL_INVESTIGATOR, Cedars-Sinai Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-17

Study Completion Date2027-02

Study Record Updates

Study Start Date2023-10-17

Study Completion Date2027-02

Terms related to this study

Keywords Provided by Researchers

Lifestyle intervention
Single RNA sequencing
Cell Senescence

Additional Relevant MeSH Terms

Obesity
Healthy Lifestyle