NCT05653258

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

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

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

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).

Detailed description

All participants after consent and enrollment will undergo adipose tissue single nuclei RNA sequencing and metabolic phenotyping. Subjects will undergo glucose tolerance testing to document glucose tolerance status. Each subject will be provided an accelerometer to be worn on their dominant wrist for 7 days for assessment of habitual activity. A dietitian will teach them to utilize the SmartIntake3 smartphone food picture application (app) for a 7-day food record. The app will be used to record amount of each meal consumed in order to determine daily food and beverage and supplement intake and quantity for dietary composition analysis. DEXA analysis will be performed to measure lean and fat body mass. Subjects will undergo evaluation of physical function/performance, including the Short Physical Performance Battery (SPPB) and VO2 peak testing for assessment of aerobic capacity. The SPPB will be done in older adults only. The NIH Patient-Reported Outcomes Measurement System (PROMIS) will be used to measure participants' self-report of symptoms, function, and health-related quality of life in the domains of physical, mental and social health. All subjects will undergo a two-step euglycemic insulin clamp and indirect calorimetry. Only older obese participants will continue to the randomization to likestyle intervention, senolytic agents or placebo.

Conditions

• Obesity
• Healthy Lifestyle

Interventions

Type	Name	Description
OTHER	Lifestyle Intervention	1. Exercise: Subjects will undergo a combined aerobic and resistance exercise intervention. The investigators propose a multi-modal training program because they improve metabolic outcomes and adding resistance training reduces the risk of muscle loss during weight loss. Subjects will exercise in the gym for three sessions per week for 10 weeks under supervision of an exercise physiologist. On each session, aerobic exercise will be followed by resistance exercise. 2. Diet: The aim of the dietary intervention is to reduce caloric intake sufficient to result in 8-10% weight loss, while incorporating behavioral and dietary strategies to maximize adherence and to minimize risk of muscle and bone loss. Subjects will attend small-group sessions led by a dietitian for changing their dietary composition to follow American Heart Association (AHA)/American College of Cardiology (ACC) guidelines.
DRUG	Dasatinib 100 MG	100 mg of dasatinib (D) daily for 3 consecutive days plus quercetin (Q) for the same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.
DRUG	Quercetin 1000mg	Quercetin (Q) (4) 250 mg capsules daily (total 1000 mg daily) plus dasatinib (D) same 3 consecutive days, followed by a 25-day (+/- 2 day) no-drug period to complete a single round. This will be repeated twice more until completing 3 rounds total in approximately 10 consecutive weeks.
DRUG	Placebo	Subjects will receive a placebo (methylcellulose) to provide a similar mass, number of tablets/ capsules, and frequency as the senolytic arm.
PROCEDURE	Abdominal adipose tissue biopsy	All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq

Timeline

• Start date: 2023-10-17
• Primary completion: 2027-02-01
• Completion: 2028-02-01
• First posted: 2022-12-16
• Last updated: 2026-03-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study