Dasatinib + Quercetin for Obesity

Overseen By Arianne Aslamy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Anti-arrhythmics, Anti-coagulants, Quinolones, others

Disqualifiers: Diabetes, Heart disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments to improve health in obese individuals by examining their effects on body tissue and metabolic functions, such as insulin sensitivity and glucose tolerance. Participants will be divided into three groups: one will try a lifestyle intervention, another will receive a combination of Dasatinib (a drug) and Quercetin (a supplement) tested for their potential to remove harmful cells, and the third will receive a placebo. The trial seeks older adults over 65 who are obese, sedentary (exercising less than 1.5 hours a week), and do not have diabetes. Participants must be generally healthy, without major heart, liver, or kidney conditions, and not currently using certain medications or substances. As a Phase 2, Phase 3 trial, this study measures treatment effectiveness and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking health solutions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like anti-arrhythmics, anti-platelets, anti-coagulants, quinolone antibiotics, weight loss medications, systemic steroids, immunosuppressants, or potentially senolytic agents within 6 months before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Dasatinib and Quercetin has been tested for safety in humans. One study suggested that using these treatments together for six months is generally safe. They may also help with aging-related issues by strengthening the immune system and improving gut health. However, no specific safety information exists for this combination in people with obesity.

In mice, this combination temporarily improved how the body handles insulin and sugar. However, another study found that it could worsen liver disease in a certain type of mouse.

Due to these mixed results in animals and the lack of detailed safety information for humans, participants should discuss any concerns with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Dasatinib and Quercetin for obesity because these treatments offer something new compared to the usual diet, exercise, and medication options. Unlike standard therapies that mainly focus on calorie reduction or fat absorption, Dasatinib and Quercetin target cellular aging and inflammation, which are underlying contributors to obesity. Dasatinib is a tyrosine kinase inhibitor, traditionally used in cancer treatment, but here it is being explored for its potential to clear out senescent cells that may impact metabolism negatively. Quercetin, a plant pigment, is known for its antioxidant properties and complements Dasatinib by reducing inflammation. Together, they could offer a novel approach to tackling obesity from the inside out, rather than just managing its symptoms.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that combining Dasatinib and Quercetin might help treat obesity. In studies with mice, this combination improved insulin and sugar management, crucial for addressing obesity. Other research with nonhuman primates suggested that this treatment might positively affect aging and inflammation, often linked to obesity. Reports also indicated better cholesterol levels and reduced appetite in humans, important factors for weight control. Overall, these findings suggest that Dasatinib and Quercetin, studied in this trial, could help with obesity by addressing several related health issues. ^{1 2 3 5 6}

Who Is on the Research Team?

Nicolas Musi, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for lean individuals aged 18-30 or those over 65 with a healthy BMI, from any race and living in the community. They must be sedentary, nondiabetic, not pregnant or breastfeeding, and willing to use effective contraception. Participants should have normal blood sugar levels and ECG readings.

Inclusion Criteria

I am using or willing to use a highly effective form of birth control during and after the study.

Your ECG (heart test) results need to be in specific ranges, and your heart tracing needs to look normal, unless the doctor thinks any abnormalities are not important for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline biopsies of subcutaneous abdominal adipose tissue for cellular/molecular profiling via snRNA-seq and metabolic/physiological assessments

1 week

1 visit (in-person)

Randomization and Intervention

Older obese participants are randomized into lifestyle intervention, senolytics, or placebo groups

14 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abdominal adipose tissue biopsy
• Dasatinib 100 MG
• Lifestyle Intervention
• Placebo
• Quercetin 1000mg

Trial Overview The study tests how lifestyle changes compare to senolytics (Dasatinib plus Quercetin) versus placebo in older obese adults. It involves baseline biopsies of belly fat for cellular analysis and checks on insulin sensitivity, glucose tolerance, and β-cell function.

How Is the Trial Designed?

Group I: Younger Obese Group Experimental Treatment 1 Intervention

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

Group II: Younger Lean Group Experimental Treatment 1 Intervention

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

Group III: Older Obese Group Experimental Treatment 5 Interventions

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

Group IV: Older Lean Group Experimental Treatment 1 Intervention

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

Dasatinib 100 MG is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Sprycel for:

• Chronic myeloid leukemia
• Acute lymphoblastic leukemia

Approved in United States as Sprycel for:

• Chronic myeloid leukemia
• Acute lymphoblastic leukemia

Approved in Canada as Sprycel for:

• Chronic myeloid leukemia
• Acute lymphoblastic leukemia

Approved in Japan as Sprycel for:

• Chronic myeloid leukemia
• Acute lymphoblastic leukemia

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Obesity affects over half a billion people globally, and while lifestyle changes are essential for management, they often do not lead to sustained weight loss, highlighting the need for additional interventions.

FDA-approved medications for obesity, such as orlistat and liraglutide, can provide an extra 5-10% weight loss when combined with lifestyle changes, which can significantly improve cardiovascular and metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of obesity: Available medications and drugs under investigation. Pilitsi, E., Farr, OM., Polyzos, SA., et al.[2019]

A study involving 26 obese women showed that brief lifestyle modifications provided by a physician during short visits were as effective as traditional group behavior modification in achieving significant weight loss over one year (13.9 kg vs. 15.4 kg).

Both treatment approaches led to notable improvements in lipids, lipoproteins, mood, and appetite, suggesting that effective obesity management can be integrated into primary care with minimal time commitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle modification in the pharmacologic treatment of obesity: a pilot investigation of a potential primary care approach. Wadden, TA., Berkowitz, RI., Vogt, RA., et al.[2019]

Lifestyle changes like diet, exercise, and behavioral therapy are essential for treating obesity, and if these do not lead to a 5% weight loss in 3 to 6 months, medications may be considered for patients with a BMI of 30 or higher, or 27 with related health issues.

Current obesity medications like orlistat, sibutramine, and rimonabant can lead to moderate weight loss and improved cardiovascular health, particularly enhancing glucose metabolism, but their side effects must be carefully evaluated before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. Hamann, A.[2021]

The orlistat-resveratrol (O-R) combination led to a significant weight loss of -6.82 kg over 6 months, outperforming the placebo group, which lost only -3.50 kg.

The O-R combination also resulted in notable improvements in BMI, waist circumference, fat mass, and serum biochemical markers, indicating its efficacy in treating obesity compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. Arzola-Paniagua, MA., García-Salgado López, ER., Calvo-Vargas, CG., et al.[2018]

The combination of phentermine and topiramate is currently the most effective FDA-approved treatment for obesity, followed by lorcaserin and bupropion/naltrexone.

Effective obesity management should consider not only medication efficacy but also comorbidities, drug interactions, and personalized treatment approaches based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Obesity Treatments Including Pharmacogenetic and Nutrigenetic Approaches. Solas, M., Milagro, FI., Martínez-Urbistondo, D., et al.[2018]

Quercetin effectively reduces the release of MIP-1α, a key chemokine involved in obesity-induced inflammation, from both adipocytes and macrophages, which may help mitigate inflammation in adipose tissue.

The mechanism by which quercetin exerts its anti-inflammatory effects includes downregulating specific receptors (CCR1/CCR5) and inhibiting critical signaling pathways (JNK, p38 MAPK, and IKK), suggesting it could be a beneficial treatment for obesity-related inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quercetin suppresses MIP-1α-induced adipose inflammation by downregulating its receptors CCR1/CCR5 and inhibiting inflammatory signaling. Noh, HJ., Kim, CS., Kang, JH., et al.[2021]

Quercetin effectively inhibits the growth of both imatinib-resistant and imatinib-sensitive chronic myeloid leukemia cell lines, inducing apoptosis and causing cell cycle arrest at the G2/M phase after 24 hours of treatment with 25 µmol/L.

The mechanism of action involves increased DNA damage, indicated by enhanced γ-H2AX expression, and the up-regulation of phosphorylated JNK (p-JNK), suggesting that quercetin may provide a therapeutic option for overcoming imatinib resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of Quercetin on Chronic Myeloid Leukemia Cell Line Resistant to Imatinib and Its Mechanism]. Lu, HY., Chen, J., DU, SH., et al.[2018]

In a study using BK5.IGF-1 transgenic mice, a diet supplemented with quercetin for 20 weeks delayed the onset of skin tumors by 2 weeks and reduced the number of tumors by 35%, indicating its potential as a cancer preventive agent.

Quercetin was found to inhibit IGF-1 signaling by suppressing the phosphorylation of key proteins involved in the pathway, which suggests that its anticancer effects are linked to the modulation of IGF-1 receptor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor (IGF)-1 signaling in mouse skin cancer. Jung, M., Bu, SY., Tak, KH., et al.[2021]

Modest weight loss of about 5% through dietary changes and increased activity can significantly reduce the risk of obesity-related diseases and delay the onset of type 2 diabetes in patients with a BMI of 27 or higher.

Weight loss medications can enhance adherence to lifestyle changes and lead to meaningful improvements in health outcomes, but careful selection and understanding of the benefits and risks of these medications are essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical effectiveness of weight loss drugs. Wittert, G., Caterson, I., Finer, N.[2014]

Lifestyle interventions that combine dietary changes, physical activity support, and weight management education are the first-line treatment for obesity, emphasizing their importance in addressing the global obesity epidemic.

The chapter highlights the need for personalized weight management programs to enhance effectiveness and long-term adherence, given the significant health risks associated with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight Loss Strategies. Roberts, SB., Anton, S., Dao, MC.[2022]

Flavonoids-containing supplements significantly reduced insulin resistance (IR) in overweight and obese participants, as shown by a decrease in HOMA-IR scores across 25 randomized controlled trials involving 1950 subjects.

The supplements also led to significant improvements in various metabolic risk factors, including reductions in fasting blood glucose, triglycerides, and body weight, without increasing the risk of adverse effects compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of flavonoids-containing supplements on insulin resistance and associated metabolic risk factors in overweight and obese subjects: a systematic review and meta-analysis of 25 randomized controlled trials. Yao, J., Zhang, Y., Zhao, J., et al.[2022]

Quercetin (Qu) effectively inhibits the proliferation of imatinib-resistant KBM7R cells with the T315I mutation, showing an IC50 of 241.7 μmol/L after 48 hours of treatment.

Qu induces apoptosis and cell cycle arrest in KBM7R cells, likely through the inhibition of the Wnt/β-catenin signaling pathway and its downstream targets, suggesting a potential therapeutic role for Qu in overcoming resistance in CML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quercetin Inhibits KBM7R Cell Proliferation through Wnt/β-Catenin Signaling. Li, W., Yu, Y., Cheng, H., et al.[2023]

A comprehensive lifestyle modification program can lead to an approximate 10% weight loss over 16 to 26 weeks, as shown in recent randomized controlled trials, including the Diabetes Prevention Program.

Long-term weight maintenance is enhanced by ongoing support from therapists, whether in person or through various communication methods, along with high physical activity levels and low-calorie, portion-controlled meals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of lifestyle modification for long-term weight control. Wadden, TA., Butryn, ML., Byrne, KJ.[2022]

In a 14-year study of 4280 men and women aged 55-69, higher intake of flavonoids, particularly flavonols/flavones and catechins, was associated with a smaller increase in BMI among women, suggesting a potential antiobesity effect.

While women with the highest flavonoid intake had a significantly lower increase in BMI compared to those with the lowest intake, no significant differences were found in men, indicating that the benefits of flavonoids on body weight may be more pronounced in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher dietary flavone, flavonol, and catechin intakes are associated with less of an increase in BMI over time in women: a longitudinal analysis from the Netherlands Cohort Study. Hughes, LA., Arts, IC., Ambergen, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7343475/

Transient metabolic improvement in obese mice treated ... Mice treated with both navitoclax and D/Q showed an improvement of their insulin sensitivity and glucose tolerance during a short period of time.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37261678/

Long-term dasatinib plus quercetin effects on aging outcomes ... Long-term dasatinib plus quercetin effects on aging outcomes and inflammation in nonhuman primates: implications for senolytic clinical trial ...

3. withpower.com withpower.com/trial/early-phase-1-obesity-1-2023-a0556

Dasatinib + Quercetin for Obesity Both treatment approaches led to notable improvements in lipids, lipoproteins, mood, and appetite, suggesting that effective obesity management can be ...

4. biosignaling.biomedcentral.com biosignaling.biomedcentral.com/articles/10.1186/s12964-021-00731-0

and age-dependent liver disease progression by senolytic ... Dasatinib + Quercetin (D + Q) worsens liver disease progression in the diethylnitrosamine (DEN) / high fat diet (HFD) mouse model. Cellular ...

5. nature.com nature.com/articles/s41467-021-25453-2

Long-term treatment with senolytic drugs Dasatinib and ... We explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090955624017203

Metabolism and Disposition of Dasatinib after Oral ... Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.