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

Launched by CEDARS-SINAI MEDICAL CENTER · Dec 7, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of different treatments on older adults who are obese. The researchers want to better understand the cells in fat tissue and how they relate to health conditions like obesity. Participants will have a small sample of fat taken from their abdomen and will be tested for how well their bodies process sugar and insulin. There are three groups in the study: one group will receive lifestyle coaching, another will take a medication called senolytics aimed at reducing aging cells, and the last group will receive a placebo (a harmless pill with no active ingredients).

To be eligible, participants should be between 65 and 74 years old, overweight, and not very active, with less than 1.5 hours of exercise per week. They should not have diabetes or other serious health conditions, and women of childbearing age must use effective birth control during the study. Participants can expect to undergo initial tests and then be assigned to one of the three treatment groups, where they will receive support and monitoring throughout the trial. This study is currently recruiting, and it aims to provide valuable insights into managing obesity in older adults.

Gender

ALL

Eligibility criteria

• Inclusion 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:
• • A documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy Use of a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency (implantable progesterone-only hormone contraception, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner) during the intervention period of the study and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug.
• • Use of a contraceptive method that is highly effective (with a failure rate of \<1% per year), with high user dependency, (oral/intravaginal/injectable combined estrogen and progesterone contraception, oral/injectable progesterone only hormone contraception, sexual abstinence) during the intervention period and for at least 30 days after the last dose of study intervention to eliminate any reproductive safety risk of the study drug. In addition to the highly effective methods: male or female condom with or without spermicide; cervical cap, diaphragm, or sponge with spermicide; a combination of male condom with either cervical cap, diaphragm, or sponge with spermicide.
• 8. ECG value after 10 minutes of resting in the supine position in the following ranges:
• • 120ms\<PR\<220ms: QRS\<120ms; QTc\<430ms for males and QTc\<450ms for females and normal ECG tracing, unless the investigator considers the ECG abnormality to be not clinically relevant.
• Exclusion Criteria:
• • 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.

Trial Officials