Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans
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ClinicalTrials.gov Identifier: NCT04313634 |
Recruitment Status :
Active, not recruiting
First Posted : March 18, 2020
Last Update Posted : March 29, 2023
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Condition or disease | Intervention/treatment | Phase |
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Healthy | Drug: Dasatinib Drug: Quercetin Drug: Fisetin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 120 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Supportive Care |
Official Title: | Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans: A Phase 2, Single-Center, 20-week, Open-Label, Randomized Controlled Trial. |
Actual Study Start Date : | June 9, 2020 |
Estimated Primary Completion Date : | June 2023 |
Estimated Study Completion Date : | June 2023 |

Arm | Intervention/treatment |
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Experimental: Dasatinib plus Quercetin Treatment Goup
Subjects will receive Dasatinib (D; 100 mg for two days) plus Quercetin (Q; 1000 mg total daily for three consecutive days taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention
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Drug: Dasatinib
Dasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated
Other Name: Sprycel Drug: Quercetin Quercetin will be supplied as quercetin phytosome (sophora japonica concentrate (leaf) / phosphatidylcholine complex from Sunflower) 250 mg |
Experimental: Fisetin Treatment Group
Subjects will receive Fisetin (F; ~20 mg/kg/day for three consecutive days) taken orally on an intermittent schedule (starting every 28 days) with no-therapy periods in between dosing regimens, repeated every 28 days over 20 weeks, resulting in five total dosing periods throughout the entire intervention
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Drug: Fisetin
Fisetin will be supplied in 100 mg capsules to be administered orally |
No Intervention: Untreated Control Group
Subjects will not receive any intervention
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- Percent Changes in C-terminal telopeptide of type I collagen [CTX] [ Time Frame: Baseline, 20 weeks ]Percent changes in serum bone turnover markers C-terminal telopeptide of type I collagen [CTX]
- Percent Changes in amino-terminal propeptide of type I collagen [P1NP] [ Time Frame: Baseline, 20 weeks ]Percent changes in serum bone turnover markers amino-terminal propeptide of type I collagen [P1NP]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 60 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Able and willing to provide informed consent.
- Normal postmenopausal women
- Aged ≥60 years
Exclusion Criteria:
- Hemoglobin A1c ≥8.0% at screening
- Subjects who are type II diabetic and on insulin
- Abnormal screening labs (see below)
- Presence of significant liver (total bilirubin, AST, ALT, or alkaline phosphatase >2x upper normal limit) or kidney disease (eGFR<30 ml/min/1.73 m2 (using the cystatin C blood levels for analysis)
- Presence of a clinical diagnosis of heart failure
- Known active malignancy (including myeloma)
- Current diagnosis of malabsorption or undergoing treatment for malabsorption disease
- If any of the laboratory blood work drawn at the study visits return with lab values outside of the "normal limits" or show a significant change from a previous value, a repeat blood draw would be done before the subject is excluded.
- Gastric bypass/reduction
- Hyperthyroidism
- Acromegaly
- Cushing's syndrome
- Hypopituitarism
- Subjects with a fracture within the past six months
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Undergoing treatment with any medications that affect bone turnover, including the following:
- adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr), anticonvulsant therapy (within the previous year),
- calcium supplementation of > 1200 mg/d (within the preceding 3 months),
- bisphosphonates (within the past 3 yrs),
- denosumab,
- estrogen (E) therapy or treatment with a selective E receptor modulator, or teriparatide (within the past yr)
- QTc >450 msec
- Inability to provide consent
- Inability to tolerate oral medication
- Current diagnosis of hypo- or hyperparathyroidism or currently undergoing treatment for the disease
- Subjects on therapeutic doses of anti-coagulants (e.g. warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc)
- Subjects with hypovitaminosis D (25-hydroxyvitamin D [25(OH)D] <20 ng/ml, whose level does not improve above 20 ng/ml after two courses of 8-week treatment of 1000 IU/d of Vitamin D. They will be referred to their primary provider should this occur.
- Subjects taking anti-arrhythmic medications known to cause QTc prolongation
- Subjects taking potentially senolytic agents within the last 6 months: Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax
- Subjects currently taking drugs that induce cellular senescence: alkylating agents, anthracyclines, platins, other chemotherapy
- Subjects taking H2 antagonists, unless randomized to the control group
- Tyrosine kinase inhibitor therapy
- Subjects not having a PBTL p16INK4a mRNA expression level >95 percentile of young female controls (this cut-off is depicted by the dotted line in Fig. 6)
- Known hypersensitivity or allergy to Dasatinib orQuercetin
- Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), Antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir), Rifampin
- If the DXA assessment reveals a spine or femur neck T-score < -2.5, the participant will be advised of this. She would then be given the option of withdrawing from the study to immediately start an osteoporosis drug through her primary care physician or continue in the study and defer osteoporosis drug treatment for the duration of the study (20 weeks). Given that osteoporosis is a chronic, long-term disease, the 20-week deferral would pose a minimal risk to the participant and she would be free to make this choice.
- Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). If antifungals are necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic.
- Subjects taking strong inhibitors of CYP3A4
- Subjects on antiplatelet agents (Clopidogrel [Plavix]; Dipyridamole + Asprin [Aggrenox]; Ticagrelor [Brilinta]; Prasugrel [Effient]; Ticlopidine [Ticlid] or Other) who are unable or unwilling to reduce or hold therapy prior to and during the study drug dosing periods. Subjects may continue their previous regimen between study drug dosing periods.
- Subjects on quinolone antibiotic therapy for treatment or for prevention of infections within ten days.
- Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two days before and during the study drug dosing periods.
- Subjects with clinically evident fluid retention
- Subjects with evidence of right heart strain on ECG
- Subjects with a history of pulmonary hypertension
- Subjects with an abnormal Complete Blood Count (clinically insignificant changes would be acceptable based on the judgement of the investigators)
- Presence of any condition the Investigator believes would place the subject at risk or would preclude the subject from successfully completing all aspects of the trial.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04313634
United States, Minnesota | |
Mayo Clinic in Rochester | |
Rochester, Minnesota, United States, 55905 |
Principal Investigator: | Sundeep Khosla, MD | Mayo Clinic |
Responsible Party: | Sundeep Khosla, M.D., Principal Investigator, Mayo Clinic |
ClinicalTrials.gov Identifier: | NCT04313634 |
Other Study ID Numbers: |
18-010546 |
First Posted: | March 18, 2020 Key Record Dates |
Last Update Posted: | March 29, 2023 |
Last Verified: | March 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Dasatinib Quercetin Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Antioxidants Protective Agents Physiological Effects of Drugs |