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

Trial Summary

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.

What data supports the effectiveness of the treatment Dasatinib + Quercetin for Obesity?

Lifestyle modifications, such as changes in diet and physical activity, have been shown to help people lose about 10% of their initial weight in 16 to 26 weeks. Quercetin has demonstrated anticancer properties by inhibiting certain cell growth signals, which might suggest potential benefits in weight management, although more research is needed to confirm its effectiveness for obesity. ^{1 2 3 4 5}

Is the combination of Dasatinib and Quercetin safe for humans?

The research does not provide specific safety data for the combination of Dasatinib and Quercetin in humans, but Quercetin has been studied for its effects on inflammation and metabolic factors in obesity, suggesting it is generally considered safe in these contexts. ^{6 7 8 9 10}

How is the Dasatinib + Quercetin treatment for obesity different from other treatments?

The Dasatinib + Quercetin treatment for obesity is unique because it combines a cancer drug (Dasatinib) and a plant compound (Quercetin) with lifestyle interventions, which is different from the typical weight loss drugs that target appetite or fat absorption. This novel approach may offer a new mechanism of action by potentially affecting cellular processes related to aging and inflammation, which are not addressed by current obesity medications. ^{4 11 12 13 14}

What is the purpose of 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).

Research Team

Nicolas Musi, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of lifestyle modification for long-term weight control. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor (IGF)-1 signaling in mouse skin cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Lifestyle modification in the pharmacologic treatment of obesity: a pilot investigation of a potential primary care approach. [2019]

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The clinical effectiveness of weight loss drugs. [2014]

5. Germany pubmed.ncbi.nlm.nih.gov

Weight Loss Strategies. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Quercetin suppresses MIP-1α-induced adipose inflammation by downregulating its receptors CCR1/CCR5 and inhibiting inflammatory signaling. [2021]

7. China pubmed.ncbi.nlm.nih.gov

[Effects of Quercetin on Chronic Myeloid Leukemia Cell Line Resistant to Imatinib and Its Mechanism]. [2018]

8. United States 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. [2023]

9. Switzerland 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Quercetin Inhibits KBM7R Cell Proliferation through Wnt/β-Catenin Signaling. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Precision Obesity Treatments Including Pharmacogenetic and Nutrigenetic Approaches. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of obesity: Available medications and drugs under investigation. [2019]