HealthyPhase 2NCT04313634
Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans
A Phase 2 study testing Dasatinib, Quercetin and Fisetin in people with Healthy, run by Sundeep Khosla, M.D. at 1 site in United States.
Trial summary
To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women. Read more about this study
- Who is it for?
- Ages 60 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dasatinib, Quercetin and Fisetin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jun 2020to 6 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Able and willing to provide informed consent.
- Normal postmenopausal women
- Aged ≥60 years
Who cannot join
- Hemoglobin A1c ≥8.0% at screening
- Subjects who are type II diabetic and on insulin
- Abnormal screening labs: Calcium >10.1 mg/dL, Phosphorus >4.7 mg/dL, Thyroid stimulating hormone (TSH) level <0.3mU/L, Fasting blood glucose >200 mg/dL.
- 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). If any elevation were to be noted (2x the normal limit), the study participant would stop treatment and have levels re-drawn in a month, per the clinical judgement of the investigator
- Presence of a clinical diagnosis of heart failure
- Known active malignancy (including myeloma)
Show all 44Show fewer
- 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
- 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, except for use of topical steroid creams or gels or inhaled steroids), anticonvulsant therapy (within the previous year), include only those taking Carbamazepine, Phenobarbital and Phenytoin,
- 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 4-week treatment of 50,000 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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.
To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel
Dasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated
QuercetinDrug
Quercetin will be supplied as quercetin phytosome (sophora japonica concentrate (leaf) / phosphatidylcholine complex from Sunflower) 250 mg
FisetinDrug
Fisetin will be supplied in 100 mg capsules to be administered orally
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib plus Quercetin Treatment Goup | Experimental | 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 Receives: Drug: Dasatinib; Drug: Quercetin |
| Fisetin Treatment Group | Experimental | 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 Receives: Drug: Fisetin |
| Untreated Control Group | No intervention | Subjects will not receive any intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in C-terminal Telopeptide of Type I Collagen [CTX]
Percent change in serum bone turnover markers C-terminal telopeptide of type I collagen [CTX]. The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is a biomarker used to measure the rate of bone turnover. It provides valuable information for assessing bone health and evaluating treatment responses.
Measured: Baseline, 20 weeks
Secondary outcomes (5)
Change in Bone Turnover Markers
Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.
Measured: Baseline, 2 weeks
Change in Bone Turnover Markers
Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.
Measured: Baseline, 4 weeks
Change in Bone Turnover Markers
Percent change in amino-terminal propeptide of type I collagen (P1NP). The P1NP assay measures the serum concentration of the amino-terminal propeptide of type I procollagen (P1NP). As the concentration of this extension propeptide is directly proportional to the amount of new collagen laid down in bone, it can be used to assess bone formation.
Measured: Baseline, 20 weeks
Change in Bone Mineral Density (BMD)
Percent change in BMD by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, hip ((total and femoral neck (FN), and radius (total and ultra-distal)).
Measured: Baseline, 20 weeks
Change in Plasma Senescence-associated Secretory Phenotype (SASP)
Percent change in SASP cells (representing the total senescence cell burden) present. Assessment of senescence markers in bone at baseline and 2 weeks.
Measured: Baseline, 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2020
- Study start9 Jun 2020
- Primary completion6 Jun 2023
- Study completion6 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sundeep Khosla, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sundeep Khosla, M.D., Mayo Clinic
- Investigators
- Sundeep Khosla, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04313634
- Sponsor's protocol ID
- 18-010546
- Status last verified
- Jul 2024
- First submitted
- 17 Mar 2020
- Last updated
- 22 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Farr JN, Monroe DG, Atkinson EJ, Froemming MN, Ruan M, LeBrasseur NK, Khosla S. Characterization of Human Senescent Cell Biomarkers for Clinical Trials. Aging Cell. 2025 May;24(5):e14489. doi: 10.1111/acel.14489. Epub 2025 Jan 17.
PubMed 39823170Farr JN, Atkinson EJ, Achenbach SJ, Volkman TL, Tweed AJ, Vos SJ, Ruan M, Sfeir J, Drake MT, Saul D, Doolittle ML, Bancos I, Yu K, Tchkonia T, LeBrasseur NK, Kirkland JL, Monroe DG, Khosla S. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024 Sep;30(9):2605-2612. doi: 10.1038/s41591-024-03096-2. Epub 2024 Jul 2.
PubMed 38956196
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04313634
- Acronym / sponsor ID
- 18-010546
- Conditions
- Healthy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Sundeep Khosla, M.D.University, hospital or other
- Study start
- 9 Jun 2020 (actual)
- Primary completion
- 6 Jun 2023 (actual)
- Study completion
- 6 Jun 2023 (actual)
- First posted
- 18 Mar 2020 (actual)
- Results
- Posted 22 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine if senolytic drugs reduce senescent cell burden and reduce bone resorption markers/increase bone formation markers in elderly women.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dasatinib plus Quercetin Treatment Goup | Experimental | Drug: Dasatinib, Drug: QuercetinSubjects 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 |
| Fisetin Treatment Group | Experimental | Drug: FisetinSubjects 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 |
| Untreated Control Group | No intervention | –Subjects will not receive any intervention |
Who may qualify
- Ages
- 60 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Able and willing to provide informed consent.
- Normal postmenopausal women
- Aged ≥60 years
Key exclusion criteria (44 listed)
- Hemoglobin A1c ≥8.0% at screening
- Subjects who are type II diabetic and on insulin
- Abnormal screening labs: Calcium >10.1 mg/dL, Phosphorus >4.7 mg/dL, Thyroid stimulating hormone (TSH) level <0.3mU/L, Fasting blood glucose >200 mg/dL.
- 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). If any elevation were to be noted (2x the normal limit), the study participant would stop treatment and have levels re-drawn in a month, per the clinical judgement of the investigator
- Presence of a clinical diagnosis of heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: SprycelDasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated | Drug | Dasatinib plus Quercetin Treatment Goup |
| QuercetinQuercetin will be supplied as quercetin phytosome (sophora japonica concentrate (leaf) / phosphatidylcholine complex from Sunflower) 250 mg | Drug | Dasatinib plus Quercetin Treatment Goup |
| FisetinFisetin will be supplied in 100 mg capsules to be administered orally | Drug | Fisetin Treatment Group |
Primary outcome
Change in C-terminal Telopeptide of Type I Collagen [CTX]
Time frame: Baseline, 20 weeks
Percent change in serum bone turnover markers C-terminal telopeptide of type I collagen [CTX]. The C-terminal telopeptide (CTX), also known as carboxy-terminal collagen crosslinks, is a biomarker used to measure the rate of bone turnover. It provides valuable information for assessing bone health and evaluating treatment responses.
5 secondary outcomes
Change in Bone Turnover Markers
Time frame: Baseline, 2 weeks
Change in Bone Turnover Markers
Time frame: Baseline, 4 weeks
Change in Bone Turnover Markers
Time frame: Baseline, 20 weeks
Change in Bone Mineral Density (BMD)
Time frame: Baseline, 20 weeks
Change in Plasma Senescence-associated Secretory Phenotype (SASP)
Time frame: Baseline, 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39823170Farr JN, Monroe DG, Atkinson EJ, Froemming MN, Ruan M, LeBrasseur NK, Khosla S. Characterization of Human Senescent Cell Biomarkers for Clinical Trials. Aging Cell. 2025 May;24(5):e14489. doi: 10.1111/acel.14489. Epub 2025 Jan 17.
- Derived from this study: PubMed 38956196Farr JN, Atkinson EJ, Achenbach SJ, Volkman TL, Tweed AJ, Vos SJ, Ruan M, Sfeir J, Drake MT, Saul D, Doolittle ML, Bancos I, Yu K, Tchkonia T, LeBrasseur NK, Kirkland JL, Monroe DG, Khosla S. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024 Sep;30(9):2605-2612. doi: 10.1038/s41591-024-03096-2. Epub 2024 Jul 2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sundeep Khosla, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dasatinib, Quercetin and Fisetin in people with Healthy, run by Sundeep Khosla, M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in C-terminal Telopeptide of Type I Collagen [CTX] (time frame: Baseline, 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04313634, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024.