Health Trials

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

ConditionsObesityHealthy Lifestyle
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorCedars-Sinai Medical Center

About this trial

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).

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Lifestyle Intervention

    Other 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.

  • 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.

  • 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.

  • Placebo

    Drug

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

  • Abdominal adipose tissue biopsy

    Procedure/Surgery

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

Treatment groups

160 Participants
are divided into 4 treatment groups
Group A: Younger Lean GroupOther 1 intervention
Group B: Older Lean GroupOther 1 intervention
Group C: Older Obese GroupExperimental treatment 5 interventions
Group D: Younger Obese GroupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Insulin sensitivity

Change in skeletal muscle insulin sensitivity

Time frame
Week 4 and Week 15
2

Glucose tolerance

Measurement of change in glucose tolerance using a glucose tolerance test

Time frame
Baseline to Week 14

Secondary outcomes

1

Senescence-associated secretory phenotype (SASP)

Measurement of change of SASP in adipose tissue

Time frame
Baseline to Week 16

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cedars-Sinai Medical Center

Lead sponsor

National Institute on Aging (NIA)

Collaborator

Source ClinicalTrials.gov
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