- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04313634
Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans
March 25, 2024 updated by: Sundeep Khosla, M.D.
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
120
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
60 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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: 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)
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
|
Dasatinib will be supplied as 100 mg tablet white to off-white, biconvex, oval, film- coated
Other Names:
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
|
Fisetin will be supplied in 100 mg capsules to be administered orally
|
No Intervention: Untreated Control Group
Subjects will not receive any intervention
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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]
|
Baseline, 20 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent changes in bone turnover markers
Time Frame: Baseline, 4, 8, 12, 16, 20 weeks
|
Percent Changes in amino-terminal propeptide of type I collagen [P1NP] and CTX
|
Baseline, 4, 8, 12, 16, 20 weeks
|
BMD changes
Time Frame: Baseline, 20 weeks
|
Bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, hip (total and femoral neck [FN]), and radius (total and ultra-distal).
|
Baseline, 20 weeks
|
Plasma SASP factors
Time Frame: Baseline, 4, 8, 12, 16, 20 weeks
|
Plasma SASP factors
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Baseline, 4, 8, 12, 16, 20 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sundeep Khosla, MD, Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 9, 2020
Primary Completion (Actual)
June 6, 2023
Study Completion (Estimated)
June 6, 2024
Study Registration Dates
First Submitted
March 17, 2020
First Submitted That Met QC Criteria
March 17, 2020
First Posted (Actual)
March 18, 2020
Study Record Updates
Last Update Posted (Actual)
March 27, 2024
Last Update Submitted That Met QC Criteria
March 25, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-010546
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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