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

NCT05653258 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00002506R01AG075684
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Healthy Lifestyle; Obesity

Keywords

Lifestyle intervention; Single RNA sequencing; Cell Senescence

Outcome Measures

Primary Outcomes (2)

• Insulin sensitivity

  Change in skeletal muscle insulin sensitivity

  Week 4 and Week 15

• Glucose tolerance

  Measurement of change in glucose tolerance using a glucose tolerance test

  Baseline to Week 14

Secondary Outcomes (1)

• Senescence-associated secretory phenotype (SASP)

  Baseline to Week 16

Study Arms (4)

Younger Lean Group

OTHER

Participants will be aged 18-30 years and have a BMI of 18.5 - 24.9 kg/m2

Procedure: Abdominal adipose tissue biopsy

Older Lean Group

OTHER

Participants will be over 65 years of age with a BMI of 18.5 to 24.9 kg/m2

Procedure: Abdominal adipose tissue biopsy

Older Obese Group

EXPERIMENTAL

Participants will be over 65 years of age with a BMI of 30-39.9 kg/m2.

Other: Lifestyle Intervention; Drug: Dasatinib 100 MG; Drug: Quercetin 1000mg; Drug: Placebo; Procedure: Abdominal adipose tissue biopsy

Younger Obese Group

EXPERIMENTAL

Participants will be ages 18-30 years and have a BMI OF 30.0-39.9 kg/m2

Procedure: Abdominal adipose tissue biopsy

Interventions

Lifestyle Intervention OTHER

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.

Also known as: Exercise and Diet

Older Obese Group

Dasatinib 100 MG DRUG

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.

Also known as: Sprycell

Older Obese Group

Quercetin 1000mg DRUG

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.

Older Obese Group

Placebo DRUG

Subjects will receive a placebo (methylcellulose) to provide a similar mass, number of tablets/ capsules, and frequency as the senolytic arm.

Also known as: Placebo capsule

Older Obese Group

Abdominal adipose tissue biopsy PROCEDURE

All participants will undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq

Also known as: Subcutaneous abdominal adipose tissue biopsy

Older Lean Group; Older Obese Group; Younger Lean Group; Younger Obese Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both Sexes
• Age: younger lean group 18-30 years with BMI 18.5-24.9 kg/m2; younger obese group 18-30 with BMI 30.0 -39.9; older obese group ≥ 65 years with BMI 30.0-39.9
• All races and ethnic groups
• Community dwelling
• Sedentary (≤1.5 h of exercise per week)
• Nondiabetic (fasting plasma glucose \< 126 mg/dl, 2-h glucose during oral glucose tolerance test (OGTT) \< 140mg/dl, and A1c \< 6.5%
• 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.
• ECG value after 10 minutes of resting in the supine position in the following ranges:
• ms\<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.

You may not qualify if:

• Diabetes, clinically diagnosed or HbA1c \> 6.5% and/or fasting plasma glucose \> 126 mg/dl and/or use of anti-diabetic medications.
• Participating in \> 1.5 h of structured exercise/week
• Unstable weight (\>3% change in last 3 months)
• Neurological, musculoskeletal, or other conditions that may limit subject's ability to complete study physical assessment and training
• Active autoimmune/inflammatory disease including: rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, inflammatory bowel disease
• 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.
• Active gastrointestinal disease; coagulopathy; GI bleed within 6 months

Sponsors & Collaborators

• National Institute on Aging (NIA): collaborator
• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Interventions

Exercise; Diet; Dasatinib; Quercetin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nicolas Musi, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas Musi, MD

CONTACT

210-562-6140; nicolas.musi@cshs.org

Arianne Aslamy, MD

CONTACT

424-315-0685; Arianne.Aslamy@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Investigators and subjects randomized to study drug/placebo will be blinded to which intervention they receive.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician IV

Model Details: All participants will undergo cellular/molecular profiling and older obese participants will be randomized into 3 arms.

Study Record Dates

• First Submitted: December 7, 2022
• First Posted: December 16, 2022
• Study Start: October 17, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will become available after study completion and analysis.

Locations

US (1)